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1. Copy Number Variants Are Ovarian Cancer Risk Alleles at Known and Novel Risk Loci

Author: DeVries, Amber A, Dennis, Joe, Tyrer, Jonathan P, Peng, Pei-Chen, Coetzee, Simon G, Reyes, Alberto L, Plummer, Jasmine T, Davis, Brian D, Chen, Stephanie S, Dezem, Felipe Segato, Aben, Katja KH, Anton-Culver, Hoda, Antonenkova, Natalia N, Beckmann, Matthias W, Beeghly-Fadiel, Alicia, Berchuck, Andrew, Bogdanova, Natalia V, Bogdanova-Markov, Nadja, Brenton, James D, Butzow, Ralf, Campbell, Ian, Chang-Claude, Jenny, Chenevix-Trench, Georgia, Cook, Linda S, DeFazio, Anna, Doherty, Jennifer A, Dörk, Thilo, Eccles, Diana M, Eliassen, A Heather, Fasching, Peter A, Fortner, Renée T, Giles, Graham G, Goode, Ellen L, Goodman, Marc T, Gronwald, Jacek, Webb, P, DeFazio, A, Friedlander, M, Obermair, A, Grant, P, Nagle, C, Beesley, V, Chevenix-Trench, G, Bowtell, D, Blomfield, P, Brand, A, Davis, A, Leung, Y, Nicklin, J, Quinn, M, Livingstone, K, O'Neill, H, Williams, M, Black, A, Hadley, A, Glasgow, A, Garrett, A, Rao, A, Shannon, C, Steer, C, Allen, D, Neesham, D, Otton, G, Au-Yeung, G, Goss, G, Wain, G, Gard, G, Robertson, G, Lombard, J, Tan, J, McNeilage, J, Power, J, Coward, J, Miller, J, Carter, J, Lamont, J, Wong, KM, Reid, K, Perrin, L, Milishkin, L, Nascimento, M, Buck, M, Bunting, M, Harrison, M, Chetty, N, Hacker, N, McNally, O, Harnett, P, Beale, P, Awad, R, Mohan, R, Farrell, R, McIntosh, R, Rome, R, Sayer, R, Houghton, R, Hogg, R, Land, R, Baron-Hay, S, and Paramasivum, S
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Human Genome, Genetic Testing, Clinical Research, Ovarian Cancer, Rare Diseases, Prevention, Women's Health, Cancer, Genetics, 2.1 Biological and endogenous factors, Female, Humans, Carcinoma, Ovarian Epithelial, Genome-Wide Association Study, Alleles, DNA Copy Number Variations, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Ovarian Neoplasms, OPAL Study Group, AOCS Group, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract: BackgroundKnown risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort.MethodsSingle nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer-related cell types.ResultsWe identified statistically significant risk associations with CNVs at known EOC risk genes; BRCA1 (PEOC = 1.60E-21; OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4; odds ratio [OR]HGSOC = 5.74 del), and BRCA2 (PHGSOC = 7.0E-4; ORHGSOC = 3.31 deletion). Four suggestive associations (P
Published: 2022

2. Prognostic gene expression signature for high-grade serous ovarian cancer

Author: Millstein, J, Budden, T, Goode, EL, Anglesio, MS, Talhouk, A, Intermaggio, MP, Leong, HS, Chen, S, Elatre, W, Gilks, B, Nazeran, T, Volchek, M, Bentley, RC, Wang, C, Chiu, DS, Kommoss, S, Leung, SCY, Senz, J, Lum, A, Chow, V, Sudderuddin, H, Mackenzie, R, George, J, Group, AOCS, Bowtell, D, Chenevix-Trench, G, Green, A, Webb, P, DeFazio, A, Gertig, D, Traficante, N, Fereday, S, Moore, S, Hung, J, Harrap, K, Sadkowsky, T, Pandeya, N, Malt, M, Mellon, A, Robertson, R, Bergh, T Vanden, Jones, M, Mackenzie, P, Maidens, J, Nattress, K, Chiew, YE, Stenlake, A, Sullivan, H, Alexander, B, Ashover, P, Brown, S, Corrish, T, Green, L, Jackman, L, Ferguson, K, Martin, K, Martyn, A, Ranieri, B, White, J, Jayde, V, Mamers, P, Bowes, L, Galletta, L, Giles, D, Hendley, J, Alsop, K, Schmidt, T, Shirley, H, Ball, C, Young, C, Viduka, S, Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R, Kirsten, F, Rutovitz, J, Clingan, P, Glasgow, A, Proietto, A, Braye, S, Otton, G, Shannon, J, Bonaventura, T, Stewart, J, Begbie, S, Friedlander, M, Bell, D, Baron-Hay, S, Ferrier, AA, Gard, G, Nevell, D, Pavlakis, N, Valmadre, S, Young, B, Camaris, C, Crouch, R, Edwards, L, and Hacker, N
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetic Testing, Genetics, Cancer, Ovarian Cancer, Rare Diseases, 4.2 Evaluation of markers and technologies, 4.4 Population screening, Detection, screening and diagnosis, Cystadenocarcinoma, Serous, Female, Humans, Ovarian Neoplasms, Prognosis, Proportional Hazards Models, Survival Analysis, Transcriptome, formalin-fixed paraffin-embedded, gene expression, high-grade serous ovarian cancer, overall survival, prognosis, AOCS Group, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract: BackgroundMedian overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC.Patients and methodsExpression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies.ResultsExpression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02-2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to -), 5.4 (4.6-7.0), 3.8 (3.3-4.6), 3.2 (2.9-3.7) and 2.3 (2.1-2.6) years.ConclusionThe OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.
Published: 2020

3. Atezolizumab and chemotherapy for advanced or recurrent endometrial cancer (AtTEnd): a randomised, double-blind, placebo-controlled, phase 3 trial

Author: Colombo, N, Biagioli, E, Harano, K, Galli, F, Hudson, E, Antill, Y, Choi, C, Rabaglio, M, Marmé, F, Marth, C, Parma, G, Fariñas-Madrid, L, Nishio, S, Allan, K, Lee, Y, Piovano, E, Pardo, B, Nakagawa, S, Mcqueen, J, Zamagni, C, Manso, L, Takehara, K, Tasca, G, Ferrero, A, Tognon, G, Lissoni, A, Petrella, M, Laudani, M, Rulli, E, Uggeri, S, Barretina Ginesta, M, Zola, P, Casanova, C, Arcangeli, V, Antonuzzo, L, Gadducci, A, Cosio, S, Clamp, A, Persic, M, Mcneish, I, Tookman, L, Redondo Sanchez, A, Baldini, E, Palaia, I, Benedetti Panici, P, Takahashi, N, Lombard, J, Ardizzoia, A, Bologna, A, Herrero Ibáñez, A, Musolino, A, Márquez Vázquez, R, Pietzner, K, Braicu, E, Heinzelmann-Schwarz, V, Powell, M, Yokoyama, Y, Baron-Hay, S, Abeni, C, Martin Lorente, C, Cueva, J, Trillsch, F, Heitz, F, Ataseven, B, Petru, E, Heubner, M, Sadozye, A, Dubey, S, Tazbirkova, A, Tiley, S, Chrystal, K, Kim, S, Fehr, M, Scatchard, K, Anand, A, Taylor, A, Watary, H, Enomoto, T, Yoshihara, K, Selva-Nayagam, S, Karki, B, Harrison, M, Wilkinson, K, Goh, J, Glasgow, A, Chantrill, L, Lee, C, Bertolini, A, Narducci, F, Bellotti, G, Fusco, V, Aebi, S, Del Grande, M, Colombo, I, Tokunaga, H, Shigeta, S, Goss, G, Siow, Z, Steer, C, Lin, H, Colombo N., Biagioli E., Harano K., Galli F., Hudson E., Antill Y., Choi C. H., Rabaglio M., Marmé F., Marth C., Parma G., Fariñas-Madrid L., Nishio S., Allan K., Lee Y. C., Piovano E., Pardo B., Nakagawa S., McQueen J., Zamagni C., Manso L., Takehara K., Tasca G., Ferrero A., Tognon G., Lissoni A. A., Petrella M., Laudani M. E., Rulli E., Uggeri S., Barretina Ginesta M. P., Zola P., Casanova C., Arcangeli V., Antonuzzo L., Gadducci A., Cosio S., Clamp A., Persic M., McNeish I., Tookman L., Redondo Sanchez A., Baldini E., Palaia I., Benedetti Panici P., Takahashi N., Lombard J., Ardizzoia A., Bologna A., Herrero Ibáñez A. M., Musolino A., Márquez Vázquez R., Pietzner K., Braicu E., Heinzelmann-Schwarz V. A., Powell M., Yokoyama Y., Baron-Hay S., Abeni C., Martin Lorente C., Cueva J. F., Trillsch F., Heitz F., Ataseven B., Petru E., Heubner M. L., Sadozye A. H., Dubey S., Tazbirkova A., Tiley S., Chrystal K., Kim S. W., Fehr M., Scatchard K., Anand A., Taylor A., Watary H., Enomoto T., Yoshihara K., Selva-Nayagam S., Karki B., Harrison M., Wilkinson K., Goh J., Glasgow A., Chantrill L., Lee C., Bertolini A., Narducci F., Bellotti G., Fusco V., Aebi S., Del Grande M., Colombo I., Tokunaga H., Shigeta S., Goss G., Siow Z. R., Steer C., Lin H., Colombo, N, Biagioli, E, Harano, K, Galli, F, Hudson, E, Antill, Y, Choi, C, Rabaglio, M, Marmé, F, Marth, C, Parma, G, Fariñas-Madrid, L, Nishio, S, Allan, K, Lee, Y, Piovano, E, Pardo, B, Nakagawa, S, Mcqueen, J, Zamagni, C, Manso, L, Takehara, K, Tasca, G, Ferrero, A, Tognon, G, Lissoni, A, Petrella, M, Laudani, M, Rulli, E, Uggeri, S, Barretina Ginesta, M, Zola, P, Casanova, C, Arcangeli, V, Antonuzzo, L, Gadducci, A, Cosio, S, Clamp, A, Persic, M, Mcneish, I, Tookman, L, Redondo Sanchez, A, Baldini, E, Palaia, I, Benedetti Panici, P, Takahashi, N, Lombard, J, Ardizzoia, A, Bologna, A, Herrero Ibáñez, A, Musolino, A, Márquez Vázquez, R, Pietzner, K, Braicu, E, Heinzelmann-Schwarz, V, Powell, M, Yokoyama, Y, Baron-Hay, S, Abeni, C, Martin Lorente, C, Cueva, J, Trillsch, F, Heitz, F, Ataseven, B, Petru, E, Heubner, M, Sadozye, A, Dubey, S, Tazbirkova, A, Tiley, S, Chrystal, K, Kim, S, Fehr, M, Scatchard, K, Anand, A, Taylor, A, Watary, H, Enomoto, T, Yoshihara, K, Selva-Nayagam, S, Karki, B, Harrison, M, Wilkinson, K, Goh, J, Glasgow, A, Chantrill, L, Lee, C, Bertolini, A, Narducci, F, Bellotti, G, Fusco, V, Aebi, S, Del Grande, M, Colombo, I, Tokunaga, H, Shigeta, S, Goss, G, Siow, Z, Steer, C, Lin, H, Colombo N., Biagioli E., Harano K., Galli F., Hudson E., Antill Y., Choi C. H., Rabaglio M., Marmé F., Marth C., Parma G., Fariñas-Madrid L., Nishio S., Allan K., Lee Y. C., Piovano E., Pardo B., Nakagawa S., McQueen J., Zamagni C., Manso L., Takehara K., Tasca G., Ferrero A., Tognon G., Lissoni A. A., Petrella M., Laudani M. E., Rulli E., Uggeri S., Barretina Ginesta M. P., Zola P., Casanova C., Arcangeli V., Antonuzzo L., Gadducci A., Cosio S., Clamp A., Persic M., McNeish I., Tookman L., Redondo Sanchez A., Baldini E., Palaia I., Benedetti Panici P., Takahashi N., Lombard J., Ardizzoia A., Bologna A., Herrero Ibáñez A. M., Musolino A., Márquez Vázquez R., Pietzner K., Braicu E., Heinzelmann-Schwarz V. A., Powell M., Yokoyama Y., Baron-Hay S., Abeni C., Martin Lorente C., Cueva J. F., Trillsch F., Heitz F., Ataseven B., Petru E., Heubner M. L., Sadozye A. H., Dubey S., Tazbirkova A., Tiley S., Chrystal K., Kim S. W., Fehr M., Scatchard K., Anand A., Taylor A., Watary H., Enomoto T., Yoshihara K., Selva-Nayagam S., Karki B., Harrison M., Wilkinson K., Goh J., Glasgow A., Chantrill L., Lee C., Bertolini A., Narducci F., Bellotti G., Fusco V., Aebi S., Del Grande M., Colombo I., Tokunaga H., Shigeta S., Goss G., Siow Z. R., Steer C., and Lin H.
Abstract: Background: At the time of AtTEnd trial design, standard treatment for advanced or recurrent endometrial cancer included carboplatin and paclitaxel chemotherapy. This trial assessed whether combining atezolizumab with chemotherapy might improve outcomes in this population. Methods: AtTEnd was a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial done in 89 hospitals in 11 countries across Europe, Australia, New Zealand, and Asia. Enrolled patients were aged 18 years or older, and had advanced or recurrent endometrial carcinoma or carcinosarcoma, an Eastern Cooperative Oncology Group performance status of 0–2, and received no previous systemic chemotherapy for recurrence. Patients were randomly assigned (2:1) using an interactive web response system (block size of six) to either atezolizumab 1200 mg or placebo given intravenously with chemotherapy (carboplatin at area under the curve of 5 or 6 and paclitaxel 175 mg/m2 intravenously on day 1 every 21 days) for 6–8 cycles, then continued until progression. Stratification factors were country, histological subtype, advanced or recurrent status, and mismatch repair (MMR) status. Participants and treating clinicians were masked to group allocation. The hierarchically tested co-primary endpoints were progression-free survival (in patients with MMR-deficient [dMMR] tumours, and in the overall population) and overall survival (in the overall population). Primary analyses were done in the intention-to-treat population, defined as all randomly assigned patients who gave their full consent to participation in the study and data processing. Safety was assessed in all patients included in the intention-to-treat population who received at least one dose of study treatment. Here, we report the primary progression-free survival and the interim overall survival results. This study is ongoing and is registered with ClinicalTrials.gov, NCT03603184. Findings: Between Oct 3, 2018, and Jan 7, 2022, 551 patients were r
Published: 2024

4. Adoption of adjuvant bisphosphonates for early breast cancer into standard clinical practice: Challenges and lessons learnt from comparison of the UK and Australian experience

Author: Porter, I., Theodoulou, E., Holen, I., Harper-Wynne, C., Baron-Hay, S., Wilson, C., and Brown, J.
Published: 2021
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5. Refined cut-off for TP53 immunohistochemistry improves prediction of TP53 mutation status in ovarian mucinous tumors: implications for outcome analyses

Author: Kang, Eun Young, Cheasley, Dane, LePage, Cecile, Wakefield, Matthew J., da Cunha Torres, Michelle, Rowley, Simone, Salazar, Carolina, Xing, Zhongyue, Allan, Prue, Bowtell, David D.L., Mes-Masson, Anne-Marie, Provencher, Diane M., Rahimi, Kurosh, Kelemen, Linda E., Fasching, Peter A., Doherty, Jennifer A., Goodman, Marc T., Goode, Ellen L., Deen, Suha, Pharoah, Paul D.P., Brenton, James D., Sieh, Weiva, Mateoiu, Constantina, Sundfeldt, Karin, Cook, Linda S., Le, Nhu D., Anglesio, Michael S., Gilks, C. Blake, Huntsman, David G., Kennedy, Catherine J., Traficante, Nadia, Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Bergh, T. Vanden, Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y.E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M.K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., O'Callaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L.F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., Zeps, N., DeFazio, Anna, Kaufmann, Scott, Churchman, Michael, Gourley, Charlie, Stephens, Andrew N., Meagher, Nicola S., Ramus, Susan J., Antill, Yoland C., Campbell, Ian, Scott, Clare L., Köbel, Martin, Gorringe, Kylie L., Ryland, Georgina L., Allan, Prue E., Alsop, Kathryn, Ananda, Sumitra, Au-Yeung, George, Böhm, Maret, Brand, Alison, Chenevix-Trench, Georgia, Christie, Michael, Chiew, Yoke-Eng, Dudley, Rhiannon, Fairweather, Nicole, Fereday, Sian, Fox, Stephen B., Hacker, Neville F., Hadley, Alison M., Hendley, Joy, Ho, Gwo-Yaw, Hunter, Sally M., Jobling, Tom W., Kalli, Kimberly R., Kaufmann, Scott H., Le Page, Cecile, McNally, Orla M., McAlpine, Jessica N., Mileshkin, Linda, Pyman, Jan, Samimi, Goli, Sharma, Ragwha, and Campbell, Ian G.
Published: 2021
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6. Prognostic gene expression signature for high-grade serous ovarian cancer

Author: Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Vanden Bergh, T., Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y.E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier,a, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M.K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., O’Callaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L.F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., Zeps, N., Millstein, J., Budden, T., Goode, E.L., Anglesio, M.S., Talhouk, A., Intermaggio, M.P., Leong, H.S., Chen, S., Elatre, W., Gilks, B., Nazeran, T., Volchek, M., Bentley, R.C., Wang, C., Chiu, D.S., Kommoss, S., Leung, S.C.Y., Senz, J., Lum, A., Chow, V., Sudderuddin, H., Mackenzie, R., George, J., Steed, H., Koziak, J.M., Köbel, M., McNeish, I.A., Goranova, T., Ennis, D., Macintyre, G., Silva De Silva, D., Ramón y Cajal, T., García-Donas, J., Hernando Polo, S., Rodriguez, G.C., Cushing-Haugen, K.L., Harris, H.R., Greene, C.S., Zelaya, R.A., Behrens, S., Fortner, R.T., Sinn, P., Herpel, E., Lester, J., Lubiński, J., Oszurek, O., Tołoczko, A., Cybulski, C., Menkiszak, J., Pearce, C.L., Pike, M.C., Tseng, C., Alsop, J., Rhenius, V., Song, H., Jimenez-Linan, M., Piskorz, A.M., Gentry-Maharaj, A., Karpinskyj, C., Widschwendter, M., Singh, N., Kennedy, C.J., Harnett, P.R., Gao, B., Johnatty, S.E., Sayer, R., Boros, J., Winham, S.J., Keeney, G.L., Kaufmann, S.H., Larson, M.C., Luk, H., Hernandez, B.Y., Thompson, P.J., Wilkens, L.R., Carney, M.E., Trabert, B., Lissowska, J., Brinton, L., Sherman, M.E., Bodelon, C., Hinsley, S., Lewsley, L.A., Glasspool, R., Banerjee, S.N., Stronach, E.A., Haluska, P., Ray-Coquard, I., Mahner, S., Winterhoff, B., Slamon, D., Levine, D.A., Kelemen, L.E., Benitez, J., Chang-Claude, J., Gronwald, J., Wu, A.H., Menon, U., Goodman, M.T., Schildkraut, J.M., Wentzensen, N., Brown, R., Berchuck, A., deFazio, A., Gayther, S.A., García, M.J., Henderson, M.J., Rossing, M.A., Beeghly-Fadiel, A., Fasching, P.A., Orsulic, S., Karlan, B.Y., Konecny, G.E., Huntsman, D.G., Bowtell, D.D., Brenton, J.D., Doherty, J.A., Pharoah, P.D.P., and Ramus, S.J.
Published: 2020
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7. Health-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician's Choice

Author: Lorusso, D, Colombo, N, Herraez, A, Santin, A, Colomba, E, Miller, D, Fujiwara, K, Pignata, S, Baron-Hay, S, Ray-Coquard, I, Shapira-Frommer, R, Kim, Y, Mccormack, M, Massaad, R, Nguyen, A, Zhao, Q, Mckenzie, J, Prabhu, V, Makker, V, Lorusso D., Colombo N., Herraez A. C., Santin A. D., Colomba E., Miller D. S., Fujiwara K., Pignata S., Baron-Hay S. E., Ray-Coquard I. L., Shapira-Frommer R., Kim Y. M., McCormack M., Massaad R., Nguyen A. M., Zhao Q., McKenzie J., Prabhu V. S., Makker V., Lorusso, D, Colombo, N, Herraez, A, Santin, A, Colomba, E, Miller, D, Fujiwara, K, Pignata, S, Baron-Hay, S, Ray-Coquard, I, Shapira-Frommer, R, Kim, Y, Mccormack, M, Massaad, R, Nguyen, A, Zhao, Q, Mckenzie, J, Prabhu, V, Makker, V, Lorusso D., Colombo N., Herraez A. C., Santin A. D., Colomba E., Miller D. S., Fujiwara K., Pignata S., Baron-Hay S. E., Ray-Coquard I. L., Shapira-Frommer R., Kim Y. M., McCormack M., Massaad R., Nguyen A. M., Zhao Q., McKenzie J., Prabhu V. S., and Makker V.
Abstract: Purpose: Lenvatinib and pembrolizumab (LEN+PEMBRO) demonstrated clinically meaningful and statistically significant improvements in efficacy versus treatment of physician's choice (TPC) in patients with advanced endometrial cancer (aEC) in the phase 3 Study 309/KEYNOTE-775. Health-related quality-of-life (HRQoL) is reported. Patients and Methods: Patients were randomly assigned to receive LEN+PEMBRO (n = 411; LEN 20 mg/day; PEMBRO 200 mg Q3W) or TPC (n = 416; doxorubicin 60 mg/m2 Q3W or paclitaxel 80 mg/m2 [weekly, 3 weeks on/1 week off]). Impact of treatment on HRQoL assessed by the global health status/quality of life (GHS/QoL) score of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) was a secondary objective; other scales of the Quality-of-Life Questionnaire (QLQ-C30), EORTC QLQ-Endometrial, 24 questions (EORTC QLQ-EN24), and EuroQoL 5 dimensions, 5 levels (EQ-5D-5L) were exploratory objectives. HRQoL was assessed on day 1 of each cycle. Completion/compliance, change from baseline, time to first and definitive deterioration were assessed. No multiplicity adjustments were applied for HRQoL endpoints. Results: The latest timepoint at which the predefined rates of completion (≥60%) and compliance (≥80%) were met was week 12. HRQoL at week 12 between treatment groups was generally similar. Time to first deterioration symptom scales favoured LEN+PEMBRO for QLQ-C30 dyspnoea, and QLQ-EN24 for poor body image, tingling/numbness, and hair loss; and TPC was favoured for QLQ-C30 pain, appetite loss, and diarrhoea, and QLQ-EN24 muscular pain. While the QLQ-C30 physical functional scale favoured TPC, other functional scales were generally similar between arms. Time to definitive deterioration favoured LEN+PEMBRO on most scales. Conclusion: HRQoL data from Study 309/KEYNOTE-775, with previously published efficacy and safety results, indicate that LEN+PEMBRO has an overall favourable benefit/risk profile versus TPC fo
Published: 2023

8. Results of PD-L1 Analysis of Women Treated with Durvalumab in Advanced Endometrial Carcinoma (PHAEDRA)

Author: Smith, D, Robledo, KP, Yip, S, Cummins, MM, Kok, P-S, Lee, YC, Friedlander, M, Baron-Hay, S, Shannon, C, Coward, J, Beale, P, Goss, G, Meniawy, T, Lombard, J, Spurdle, AB, Andrews, J, Stockler, MR, Mileshkin, L, Antill, Y, Smith, D, Robledo, KP, Yip, S, Cummins, MM, Kok, P-S, Lee, YC, Friedlander, M, Baron-Hay, S, Shannon, C, Coward, J, Beale, P, Goss, G, Meniawy, T, Lombard, J, Spurdle, AB, Andrews, J, Stockler, MR, Mileshkin, L, and Antill, Y
Abstract: Women with advanced endometrial carcinoma (EC) with mismatch repair (MMR) deficiency have improved outcomes when treated with immune checkpoint inhibitors; however, additional biomarkers are needed to identify women most likely to respond. Scores for programmed death ligand 1 (PD-L1), immunohistochemical staining of tumor (TC+), immune cells (IC+) and presence of tumor-associated immune cells (ICP) on MMR deficient (n = 34) and proficient (n = 33) EC from women treated with durvalumab in the PHAEDRA trial (ANZGOG1601/CTC0144) (trial registration number ACTRN12617000106336, prospectively registered 19 January 2017) are reported and correlated with outcome. Receiver operating characteristic (ROC) analyses and area under the ROC curve were used to determine optimal cutpoints. Performance was compared with median cutpoints and two algorithms; a novel algorithm derived from optimal cutpoints (TC+ ≥ 1 or ICP ≥ 10 or IC+ ≥ 35) and the Ventana urothelial carcinoma (UC) algorithm (either TC+ ≥ 25, ICP > 1 and IC+ ≥ 25 or ICP = 1 and IC+ = 100). The cutpoint ICP ≥ 10 had highest sensitivity (53%) and specificity (82%), being prognostic for progression-free survival (PFS) (p = 0.01), while the optimal cutpoints algorithm was associated with overall survival (p = 0.02); these results were not significant after adjusting for MMR status. The optimal cutpoints algorithm identified non-responders (p = 0.02) with high sensitivity (88%) and negative predictive value (92%), remaining significant after adjustment for MMR. Although MMR status had the strongest association with response, further work to determine the significance of ICP ≥ 10 and the novel optimal cutpoint algorithm is needed.
Published: 2023

9. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775

Author: Makker, V, Colombo, N, Herráez, A, Monk, B, Mackay, H, Santin, A, Miller, D, Moore, R, Baron-Hay, S, Ray-Coquard, I, Ushijima, K, Yonemori, K, Kim, Y, Guerra Alia, E, Sanli, U, Bird, S, Orlowski, R, Mckenzie, J, Okpara, C, Barresi, G, Lorusso, D, Makker, Vicky, Colombo, Nicoletta, Herráez, Antonio Casado, Monk, Bradley J, Mackay, Helen, Santin, Alessandro D, Miller, David S, Moore, Richard G, Baron-Hay, Sally, Ray-Coquard, Isabelle, Ushijima, Kimio, Yonemori, Kan, Kim, Yong Man, Guerra Alia, Eva M, Sanli, Ulus A, Bird, Steven, Orlowski, Robert, McKenzie, Jodi, Okpara, Chinyere, Barresi, Gianmaria, Lorusso, Domenica, Makker, V, Colombo, N, Herráez, A, Monk, B, Mackay, H, Santin, A, Miller, D, Moore, R, Baron-Hay, S, Ray-Coquard, I, Ushijima, K, Yonemori, K, Kim, Y, Guerra Alia, E, Sanli, U, Bird, S, Orlowski, R, Mckenzie, J, Okpara, C, Barresi, G, Lorusso, D, Makker, Vicky, Colombo, Nicoletta, Herráez, Antonio Casado, Monk, Bradley J, Mackay, Helen, Santin, Alessandro D, Miller, David S, Moore, Richard G, Baron-Hay, Sally, Ray-Coquard, Isabelle, Ushijima, Kimio, Yonemori, Kan, Kim, Yong Man, Guerra Alia, Eva M, Sanli, Ulus A, Bird, Steven, Orlowski, Robert, McKenzie, Jodi, Okpara, Chinyere, Barresi, Gianmaria, and Lorusso, Domenica
Abstract: Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We report the final prespecified analysis for overall survival (OS), along with updated progression-free survival (PFS) and objective response rate (ORR), and safety from the open-label, randomized, phase III Study 309/KEYNOTE-775. In total, 827 patients with advanced, recurrent, or metastatic endometrial cancer (EC) were randomly assigned to receive lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously once every 3 weeks (n = 411) or chemotherapy of the treating physician's choice (doxorubicin 60 mg/m2 intravenously once every 3 weeks or paclitaxel 80 mg/m2 intravenously once weekly [3 weeks on; 1 week off] [n = 416]). Efficacy was reported for patients with mismatch repair proficient (pMMR) tumors and all-comers, and by subgroups (histology, prior therapy, MMR status). Updated safety was also reported.Lenvatinib plus pembrolizumab showed benefits in OS (pMMR HR, 0.70; 95% CI, 0.58 to 0.83; all-comer HR, 0.65; 95% CI, 0.55 to 0.77), PFS (pMMR HR, 0.60; 95% CI, 0.50 to 0.72; all-comer HR, 0.56; 95% CI, 0.48 to 0.66), and ORR (pMMR patients, 32.4% v 15.1%; all-comers, 33.8% v 14.7%) versus chemotherapy. OS, PFS, and ORR favored lenvatinib plus pembrolizumab in all subgroups of interest. No new safety signals were observed. Lenvatinib plus pembrolizumab continued to show improved efficacy versus chemotherapy and manageable safety in patients with previously treated advanced EC.
Published: 2023

10. The PREDICT Registry Australia: A Prospective Registry to Evaluate the Clinical Utility of a Biomarker Assay on Treatment Decisions in Patients with DCIS Following Breast Conserving Surgery

Author: Zissiadis, Y., primary, Mann, G.B., additional, Speakman, D., additional, Saunders, C., additional, Pike, C., additional, de Viana, D., additional, Bochner, M., additional, French, J., additional, Dreosti, M.V., additional, Baron-Hay, S., additional, Feetham, A., additional, Kirkham, K., additional, Ryan, S., additional, Mittal, K., additional, Shivers, S., additional, and Bremer, T., additional
Published: 2022
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11. MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

Author: Block, Matthew S., Vierkant, Robert A., Rambau, Peter F., Winham, Stacey J., Wagner, Philipp, Traficante, Nadia, Tołoczko, Aleksandra, Tiezzi, Daniel G., Taran, Florin Andrei, Sinn, Peter, Sieh, Weiva, Sharma, Raghwa, Rothstein, Joseph H., Cajal, Teresa Ramón y, Paz-Ares, Luis, Oszurek, Oleg, Orsulic, Sandra, Ness, Roberta B., Nelson, Gregg, Modugno, Francesmary, Menkiszak, Janusz, McGuire, Valerie, McCauley, Bryan M., Mack, Marie, Lubiński, Jan, Longacre, Teri A., Li, Zheng, Lester, Jenny, Kennedy, Catherine J., Kalli, Kimberly R., Jung, Audrey Y., Johnatty, Sharon E., Jimenez-Linan, Mercedes, Jensen, Allan, Intermaggio, Maria P., Hung, Jillian, Herpel, Esther, Hernandez, Brenda Y., Hartkopf, Andreas D., Harnett, Paul R., Ghatage, Prafull, García-Bueno, José M., Gao, Bo, Fereday, Sian, Eilber, Ursula, Edwards, Robert P., de Sousa, Christiani B., de Andrade, Jurandyr M., Chudecka-Głaz, Anita, Chenevix-Trench, Georgia, Cazorla, Alicia, Brucker, Sara Y., Alsop, Jennifer, Whittemore, Alice S., Steed, Helen, Staebler, Annette, Moysich, Kirsten B., Menon, Usha, Koziak, Jennifer M., Kommoss, Stefan, Kjaer, Susanne K., Kelemen, Linda E., Karlan, Beth Y., Huntsman, David G., Hφgdall, Estrid, Gronwald, Jacek, Goodman, Marc T., Gilks, Blake, García, María José, Fasching, Peter A., de Fazio, Anna, Deen, Suha, Chang-Claude, Jenny, Candido dos Reis, Francisco J., Campbell, Ian G., Brenton, James D., Bowtell, David D., Benítez, Javier, Pharoah, Paul D.P., Köbel, Martin, Ramus, Susan J., Goode, Ellen L., Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Bergh, Vanden T., Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y. E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M. K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., OʼCallaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L. F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., and Zeps, N.
Published: 2018
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12. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer

Author: Makker, V, Colombo, N, Casado Herráez, A, Santin, A, Colomba, E, Miller, D, Fujiwara, K, Pignata, S, Baron-Hay, S, Ray-Coquard, I, Shapira-Frommer, R, Ushijima, K, Sakata, J, Yonemori, K, Kim, Y, Guerra, E, Sanli, U, Mccormack, M, Smith, A, Keefe, S, Bird, S, Dutta, L, Orlowski, R, Lorusso, D, Makker, Vicky, Colombo, Nicoletta, Casado Herráez, Antonio, Santin, Alessandro D, Colomba, Emeline, Miller, David S, Fujiwara, Keiichi, Pignata, Sandro, Baron-Hay, Sally, Ray-Coquard, Isabelle, Shapira-Frommer, Ronnie, Ushijima, Kimio, Sakata, Jun, Yonemori, Kan, Kim, Yong Man, Guerra, Eva M, Sanli, Ulus A, McCormack, Mary M, Smith, Alan D, Keefe, Stephen, Bird, Steven, Dutta, Lea, Orlowski, Robert J, Lorusso, Domenica, Makker, V, Colombo, N, Casado Herráez, A, Santin, A, Colomba, E, Miller, D, Fujiwara, K, Pignata, S, Baron-Hay, S, Ray-Coquard, I, Shapira-Frommer, R, Ushijima, K, Sakata, J, Yonemori, K, Kim, Y, Guerra, E, Sanli, U, Mccormack, M, Smith, A, Keefe, S, Bird, S, Dutta, L, Orlowski, R, Lorusso, D, Makker, Vicky, Colombo, Nicoletta, Casado Herráez, Antonio, Santin, Alessandro D, Colomba, Emeline, Miller, David S, Fujiwara, Keiichi, Pignata, Sandro, Baron-Hay, Sally, Ray-Coquard, Isabelle, Shapira-Frommer, Ronnie, Ushijima, Kimio, Sakata, Jun, Yonemori, Kan, Kim, Yong Man, Guerra, Eva M, Sanli, Ulus A, McCormack, Mary M, Smith, Alan D, Keefe, Stephen, Bird, Steven, Dutta, Lea, Orlowski, Robert J, and Lorusso, Domenica
Abstract: BACKGROUND Standard therapy for advanced endometrial cancer after failure of platinum-based chemotherapy remains unclear. METHODS In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced endometrial cancer who had previously received at least one platinum-based chemotherapy regimen to receive either lenvatinib (20 mg, administered orally once daily) plus pembrolizumab (200 mg, administered intravenously every 3 weeks) or chemotherapy of the treating physician’s choice (doxorubicin at 60 mg per square meter of body-surface area, administered intravenously every 3 weeks, or paclitaxel at 80 mg per square meter, administered intravenously weekly [with a cycle of 3 weeks on and 1 week off]). The two primary end points were progression-free survival as assessed on blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1, and overall survival. The end points were evaluated in patients with mismatch repair–proficient (pMMR) disease and in all patients. Safety was also assessed. RESULTS A total of 827 patients (697 with pMMR disease and 130 with mismatch repair–deficient disease) were randomly assigned to receive lenvatinib plus pembrolizumab (411 patients) or chemotherapy (416 patients). The median progression-free survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 6.6 vs. 3.8 months; hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.50 to 0.72; P<0.001; overall: 7.2 vs. 3.8 months; hazard ratio, 0.56; 95% CI, 0.47 to 0.66; P<0.001). The median overall survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 17.4 vs. 12.0 months; hazard ratio for death, 0.68; 95% CI, 0.56 to 0.84; P<0.001; overall: 18.3 vs. 11.4 months; hazard ratio, 0.62; 95% CI, 0.51 to 0.75; P<0.001). Adverse events of grade 3 or higher occurred in 88.9% of the patients who received lenvatinib plus pembr
Published: 2022

13. O008/#785 A multicenter, open-label, randomized, phase 3 study to compare the efficacy and safety of lenvatinib in combination with pembrolizumab vs treatment of physician’s choice in patients with advanced endometrial cancer: study 309/keynote-775

Author: Makker, V, primary, Colombo, N, additional, Casado Herráez, A, additional, Santin, A, additional, Colomba, E, additional, Miller, D, additional, Fujiwara, K, additional, Pignata, S, additional, Baron-Hay, S, additional, Ray-Coquard, I, additional, Shapira, R, additional, Ushijima, K, additional, Sakata, J, additional, Yonemori, K, additional, Kim, YM, additional, Guerra, EM, additional, Sanli, UA, additional, Mccormack, M, additional, Huang, J, additional, and Smith, AD, additional
Published: 2021
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14. Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial.

Author: Antill Y., Kok P.-S., Robledo K., Yip S., Cummins M., Smith D., Spurdle A., Barnes E., Lee Y.C., Friedlander M., Baron-Hay S., Shannon C., Coward J., Beale P., Goss G., Meniawy T., Lombard J., Andrews J., Stockler M.R., Mileshkin L., Antill Y., Kok P.-S., Robledo K., Yip S., Cummins M., Smith D., Spurdle A., Barnes E., Lee Y.C., Friedlander M., Baron-Hay S., Shannon C., Coward J., Beale P., Goss G., Meniawy T., Lombard J., Andrews J., Stockler M.R., and Mileshkin L.
Abstract: Background In this study, we assessed the activity of durvalumab, an antibody to programmed death ligand-1, in two cohorts of women with advanced endometrial cancers (AEC) - mismatch repair proficient (pMMR) and mismatch repair deficient (dMMR). Methods A multicenter phase two study was performed in women with AEC with pMMR tumor progressing after one to three lines of chemotherapy and women with AEC with dMMR tumor progressing after zero to three lines of chemotherapy. Mismatch repair status was based on immunohistochemistry expression. All women received durvalumab 1500 mg given every 4 weeks until progression or unacceptable toxicity. The primary endpoint was objective tumor response by RECIST V.1.1 modified for immune-based therapeutics. Results Seventy-one women were recruited: 35 dMMR and 36 pMMR. Median follow-up was 19 vs 21 months in dMMR versus pMMR, respectively. Median age was 67 years. Histology in dMMR versus pMMR included endometrioid (94% vs 57%) and serous (0% vs 31%) and was high grade in 26% vs 74%. The objective tumor response rate (OTRR) in the dMMR cohort was 47% (17/36, 95% CI 32 to 63), including 6 complete responses and 11 partial responses (PRs)) vs 3% in the pMMR cohort (1/35, 95% CI 1 to 15, PR). In the dMMR cohort, durvalumab was the first-line therapy in 58% (OTRR 57%) and the second-line therapy in 39% (OTRR 38%). Median progression-free survival was 8.3 months in the dMMR cohort vs 1.8 months in the pMMR cohort. The 12-month overall survival (OS) rate was 71% in dMMR vs 51% in pMMR, with median OS not reached for dMMR vs 12 months for pMMR. Immune-related adverse events occurred in 14 women, mostly grades 1-2. Conclusion Durvalumab monotherapy showed promising activity and acceptable safety in AEC with dMMR regardless of prior lines of chemotherapy, but activity was limited in AEC with pMMR. Trial registration numbers ANZGOG1601, ACTRN12617000106336, and NCT03015129. Copyright ©
Published: 2021

15. Refined cut-off for TP53 immunohistochemistry improves prediction of TP53 mutation status in ovarian mucinous tumors: implications for outcome analyses.

Author: Friedlander M., Russell P., Links M., Grygiel J., Hill J., Byth K., Jaworski R., Harnett P., Wain G., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Jobling T., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Bell R., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., Kaufmann S., Meagher N.S., Ramus S.J., Campbell I., Cheasley D., Wakefield M.J., Ryland G.L., Allan P.E., Alsop K., Ananda S., Anglesio M.S., Au-Yeung G., Bohm M., Bowtell D.D.L., Brand A., Chenevix-Trench G., Christie M., Chiew Y.-E., Churchman M., DeFazio A., Dudley R., Fairweather N., Fereday S., Fox S.B., Gilks C.B., Gourley C., Hacker N.F., Hadley A.M., Hendley J., Ho G.-Y., Huntsman D.G., Hunter S.M., Jobling T.W., Kalli K.R., Kaufmann S.H., Kennedy C.J., Kobel M., Le Page C., McNally O.M., McAlpine J.N., Mileshkin L., Jan Pyman, Rahimi K., Samimi G., Sharma R., Stephens A.N., Traficante N., Antill Y.C., Scott C.L., Campbell I.G., Gorringe K.L., Kang E.Y., LePage C., da Cunha Torres M., Rowley S., Salazar C., Xing Z., Allan P., Mes-Masson A.-M., Provencher D.M., Kelemen L.E., Fasching P.A., Doherty J.A., Goodman M.T., Goode E.L., Deen S., Pharoah P.D.P., Brenton J.D., Sieh W., Mateoiu C., Sundfeldt K., Cook L.S., Le N.D., Bowtell D., Green A., Webb P., Gertig D., Moore S., Hung J., Harrap K., Sadkowsky T., Pandeya N., Malt M., Mellon A., Robertson R., Bergh T.V., Jones M., Mackenzie P., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Ferguson K., Martin K., Martyn A., Ranieri B., White J., Jayde V., Mamers P., Bowes L., Galletta L., Giles D., Schmidt T., Shirley H., Ball C., Young C., Viduka S., Tran H., Bilic S., Glavinas L., Brooks J., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Friedlander M., Russell P., Links M., Grygiel J., Hill J., Byth K., Jaworski R., Harnett P., Wain G., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Jobling T., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Bell R., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., Kaufmann S., Meagher N.S., Ramus S.J., Campbell I., Cheasley D., Wakefield M.J., Ryland G.L., Allan P.E., Alsop K., Ananda S., Anglesio M.S., Au-Yeung G., Bohm M., Bowtell D.D.L., Brand A., Chenevix-Trench G., Christie M., Chiew Y.-E., Churchman M., DeFazio A., Dudley R., Fairweather N., Fereday S., Fox S.B., Gilks C.B., Gourley C., Hacker N.F., Hadley A.M., Hendley J., Ho G.-Y., Huntsman D.G., Hunter S.M., Jobling T.W., Kalli K.R., Kaufmann S.H., Kennedy C.J., Kobel M., Le Page C., McNally O.M., McAlpine J.N., Mileshkin L., Jan Pyman, Rahimi K., Samimi G., Sharma R., Stephens A.N., Traficante N., Antill Y.C., Scott C.L., Campbell I.G., Gorringe K.L., Kang E.Y., LePage C., da Cunha Torres M., Rowley S., Salazar C., Xing Z., Allan P., Mes-Masson A.-M., Provencher D.M., Kelemen L.E., Fasching P.A., Doherty J.A., Goodman M.T., Goode E.L., Deen S., Pharoah P.D.P., Brenton J.D., Sieh W., Mateoiu C., Sundfeldt K., Cook L.S., Le N.D., Bowtell D., Green A., Webb P., Gertig D., Moore S., Hung J., Harrap K., Sadkowsky T., Pandeya N., Malt M., Mellon A., Robertson R., Bergh T.V., Jones M., Mackenzie P., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Ferguson K., Martin K., Martyn A., Ranieri B., White J., Jayde V., Mamers P., Bowes L., Galletta L., Giles D., Schmidt T., Shirley H., Ball C., Young C., Viduka S., Tran H., Bilic S., Glavinas L., Brooks J., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., and Houghton R.
Abstract: TP53 mutations are implicated in the progression of mucinous borderline tumors (MBOT) to mucinous ovarian carcinomas (MOC). Optimized immunohistochemistry (IHC) for TP53 has been established as a proxy for the TP53 mutation status in other ovarian tumor types. We aimed to confirm the ability of TP53 IHC to predict TP53 mutation status in ovarian mucinous tumors and to evaluate the association of TP53 mutation status with survival among patients with MBOT and MOC. Tumor tissue from an initial cohort of 113 women with MBOT/MOC was stained with optimized IHC for TP53 using tissue microarrays (75.2%) or full sections (24.8%) and interpreted using established criteria as normal or abnormal (overexpression, complete absence, or cytoplasmic). Cases were considered concordant if abnormal IHC staining predicted deleterious TP53 mutations. Discordant tissue microarray cases were re-evaluated on full sections and interpretational criteria were refined. The initial cohort was expanded to a total of 165 MBOT and 424 MOC for the examination of the association of survival with TP53 mutation status, assessed either by TP53 IHC and/or sequencing. Initially, 82/113 (72.6%) cases were concordant using the established criteria. Refined criteria for overexpression to account for intratumoral heterogeneity and terminal differentiation improved concordance to 93.8% (106/113). In the expanded cohort, 19.4% (32/165) of MBOT showed evidence for TP53 mutation and this was associated with a higher risk of recurrence, disease-specific death, and all-cause mortality (overall survival: HR = 4.6, 95% CI 1.5-14.3, p = 0.0087). Within MOC, 61.1% (259/424) harbored a TP53 mutation, but this was not associated with survival (overall survival, p = 0.77). TP53 IHC is an accurate proxy for TP53 mutation status with refined interpretation criteria accounting for intratumoral heterogeneity and terminal differentiation in ovarian mucinous tumors. TP53 mutation status is an important biomarker to identify MB
Published: 2021

16. Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial

Author: Antill, Y, Kok, P-S, Robledo, K, Yip, S, Cummins, M, Smith, D, Spurdle, A, Barnes, E, Lee, YC, Friedlander, M, Baron-Hay, S, Shannon, C, Coward, J, Beale, P, Goss, G, Meniawy, T, Lombard, J, Andrews, J, Stockler, MR, Mileshkin, L, Antill, Y, Kok, P-S, Robledo, K, Yip, S, Cummins, M, Smith, D, Spurdle, A, Barnes, E, Lee, YC, Friedlander, M, Baron-Hay, S, Shannon, C, Coward, J, Beale, P, Goss, G, Meniawy, T, Lombard, J, Andrews, J, Stockler, MR, and Mileshkin, L
Abstract: BACKGROUND: In this study, we assessed the activity of durvalumab, an antibody to programmed death ligand-1, in two cohorts of women with advanced endometrial cancers (AEC)-mismatch repair proficient (pMMR) and mismatch repair deficient (dMMR). METHODS: A multicenter phase two study was performed in women with AEC with pMMR tumor progressing after one to three lines of chemotherapy and women with AEC with dMMR tumor progressing after zero to three lines of chemotherapy. Mismatch repair status was based on immunohistochemistry expression. All women received durvalumab 1500 mg given every 4 weeks until progression or unacceptable toxicity. The primary endpoint was objective tumor response by RECIST V.1.1 modified for immune-based therapeutics. RESULTS: Seventy-one women were recruited: 35 dMMR and 36 pMMR. Median follow-up was 19 vs 21 months in dMMR versus pMMR, respectively. Median age was 67 years. Histology in dMMR versus pMMR included endometrioid (94% vs 57%) and serous (0% vs 31%) and was high grade in 26% vs 74%. The objective tumor response rate (OTRR) in the dMMR cohort was 47% (17/36, 95% CI 32 to 63), including 6 complete responses and 11 partial responses (PRs)) vs 3% in the pMMR cohort (1/35, 95% CI 1 to 15, PR). In the dMMR cohort, durvalumab was the first-line therapy in 58% (OTRR 57%) and the second-line therapy in 39% (OTRR 38%). Median progression-free survival was 8.3 months in the dMMR cohort vs 1.8 months in the pMMR cohort. The 12-month overall survival (OS) rate was 71% in dMMR vs 51% in pMMR, with median OS not reached for dMMR vs 12 months for pMMR. Immune-related adverse events occurred in 14 women, mostly grades 1-2. CONCLUSION: Durvalumab monotherapy showed promising activity and acceptable safety in AEC with dMMR regardless of prior lines of chemotherapy, but activity was limited in AEC with pMMR. TRIAL REGISTRATION NUMBERS: ANZGOG1601, ACTRN12617000106336, and NCT03015129.
Published: 2021

17. Updated results of activity of durvalumab in advanced endometrial cancer (AEC) according to mismatch repair (MMR) status: The phase II PHAEDRA trial (ANZGOG1601).

Author: Meniawy T., Goss G., Andrews J., Mileshkin L., Kelly M., Antill Y., Kok P.S., Stockler M.R., Robledo K., Yip S., Parry M., Smith D., Spurdle A., Barnes E., Friedlander M.L., Baron-Hay S., Shannon C., Coward J., Beale P.J., Meniawy T., Goss G., Andrews J., Mileshkin L., Kelly M., Antill Y., Kok P.S., Stockler M.R., Robledo K., Yip S., Parry M., Smith D., Spurdle A., Barnes E., Friedlander M.L., Baron-Hay S., Shannon C., Coward J., and Beale P.J.
Abstract: Background: Durvalumab monotherapy has demonstrated promising objective tumour response (OTR) and safety in advanced endometrial cancer with deficient MMR. We report here updated OTR, progression-free survival (PFS) and overall survival (OS) results based on central pathology MMR review from the PHAEDRA trial. Method(s): Participants (pts) had MMR-proficient (pMMR)or -deficient (dMMR) AEC progressing after 0-3 lines of chemotherapy and were treated with durvalumab 1500mg IV Q4W. The primary endpoint was OTR (complete response [CR] or partial response [PR] byiRECIST). Secondary endpoints included PFS, OS, OTRby RECIST 1.1, adverse events, quality of life, and tertiary translational objectives to determine associations between molecular biomarkers and OTR. Result(s): 71 pts with AEC were recruited from Feb 2017toSep 2018: 36 dMMR and 35 pMMR based oncentral MMR review. Median follow-up forOS were16 vs 21 months in dMMR vspMMR pts. Median age: 67 (range 36-81); ECOG PS: 0-1in 96%, and 2in 4%. Pathology: endometrioid in 94% and 57%; serous in 0%and 31%; grade3 (most recent histology): 41% and 85% (dMMR and pMMR respectively). Durvalumab was the 1st, 2nd and subsequent line of non-hormonal therapy in 58%, 39%, and 3% pts with dMMR and 9%, 63%, and 29% pts with pMMR. Among dMMR pts, the OTR rate was 47% (17/36, 95% CI 32-63%): 6 CR,11 PRand 6stable disease (SD).OTR rate was 57% as 1st line and 38%as 2nd line. Among pMMR pts, the OTR rate was 3%(1/35, 95% CI 1-15%):1 PR and 10SD. Median PFS was 5.5 vs1.8 monthsin dMMR vs pMMR pts. 12-month OSwas 71% vs51% in dMMR vs pMMR, with median OS not reached for dMMR vs11.5 months for pMMR participants. Conclusion(s): Durvalumab monotherapy showed promising activity and safety in AEC with dMMR regardless of prior lines of chemotherapy, but there was limited evidence of activity inAEC with pMMR.
Published: 2020

18. Immune thrombocytopenic purpura (ITP) and breast cancer. Does adjuvant therapy for breast cancer improve platelet counts in ITP?

Author: Khasraw, M and Baron-Hay, S
Published: 2009

19. BRAF mutations in low-grade serous ovarian cancer and response to BRAF inhibition.

Author: Jones M., Patch A.-M., Alsop K., Ball C., Young C., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Brooks J., Traficante N., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., Links M., Grygiel J., Hill J., Brand A., Byth K., Jaworski R., Sharma R., Harnett P., Wain G., Friedlander M., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., Bell R., Jobling T., Tran H., Moujaber T., Etemadmoghadam D., Kennedy C.J., Chiew Y.E., Balleine R.L., Saunders C., Wain G.V., Gao B., Hogg R., Srirangan S., Kan C., Fereday S., Pearson J.V., Waddell N., Grimmond S.M., Dobrovic A., Bowtell D.D.L., Harnett P.R., deFazio A., Bowtell D., Chenevix-Trench G., Green A., Webb P., Gertig D., Moore S., Harrap K., Sadkowsky T., Pandeya N., Hung J., Malt M., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Ferguson K., Martin K., Martyn A., Ranieri B., Mellon A., Robertson R., Vanden Bergh T., Mackenzie P., Maidens J., Nattress K., Stenlake A., Sullivan H., White J., Jayde V., Mamers P., Bowes L., Galletta L., Giles D., Hendley J., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Jones M., Patch A.-M., Alsop K., Ball C., Young C., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Brooks J., Traficante N., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., Links M., Grygiel J., Hill J., Brand A., Byth K., Jaworski R., Sharma R., Harnett P., Wain G., Friedlander M., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., Bell R., Jobling T., Tran H., Moujaber T., Etemadmoghadam D., Kennedy C.J., Chiew Y.E., Balleine R.L., Saunders C., Wain G.V., Gao B., Hogg R., Srirangan S., Kan C., Fereday S., Pearson J.V., Waddell N., Grimmond S.M., Dobrovic A., Bowtell D.D.L., Harnett P.R., deFazio A., Bowtell D., Chenevix-Trench G., Green A., Webb P., Gertig D., Moore S., Harrap K., Sadkowsky T., Pandeya N., Hung J., Malt M., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Ferguson K., Martin K., Martyn A., Ranieri B., Mellon A., Robertson R., Vanden Bergh T., Mackenzie P., Maidens J., Nattress K., Stenlake A., Sullivan H., White J., Jayde V., Mamers P., Bowes L., Galletta L., Giles D., Hendley J., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., and Pavlakis N.
Abstract: Purpose Low-grade serous ovarian carcinoma (LGSC) responds poorly to chemotherapy and is characterized by activating mutations in the Ras sarcoma-mitogen-activated protein kinase (RAS-MAPK) pathway, including oncogenic BRAF. However, response to BRAF inhibitors is tumor-type specific. Significant improvement in survival is seen in patients with BRAF-mutant melanoma, but other cancer types, such as colorectal cancers, are generally less sensitive. We examined the frequency and characteristics of BRAF-mutated LGSC and described the response to treatment with BRAF inhibitors. Patients and Methods Mutations were assessed in LGSC (N = 65) by using targeted, exome, and whole-genome sequencing. Patient characteristics, treatment, and clinical outcome were assessed, and the median follow-up time was more than 5 years. BRAF inhibitors were trialed in two patients with a somatic BRAF V600E mutation: one patient received dabrafenib monotherapy and was monitored clinically, biochemically (cancer antigen [CA]-125 levels), and with positron emission tomography (PET) imaging. Expression of the BRAF V600E protein in this patient was assessed by immunohistochemistry. Results Among patients with LGSC, nine (13.8%) of 65 had a somatic BRAF mutation. Of the nine patients with BRAF mutation-positive LGSC, four experienced progressive disease that did not respond to conventional chemotherapy. Two of the patients experienced progression quickly and died as a result of disease progression, and two received targeted treatment. Two patients with BRAF V600E mutation received BRAF inhibitors at relapse and both achieved durable responses. Conclusion BRAF mutations are not uncommon in patients with LGSC and should be routinely tested, because BRAF inhibitors can be an effective treatment for these patients. The results highlight the need for targeted treatment in this rare tumor type, and a prospective study is needed to formally assess the response rate and clinical benefit.Copyright © 2019 Am
Published: 2019

20. Tailored NEOadjuvant epirubicin, cyclophosphamide and Nanoparticle Albumin-Bound paclitaxel for breast cancer: The phase II NEONAB trial-Clinical outcomes and molecular determinants of response

Author: Roviello, G, Murphy, C, Muscat, A, Ashley, D, Mukaro, V, West, L, Liao, Y, Chisanga, D, Shi, W, Collins, I, Baron-Hay, S, Patil, S, Lindeman, G, Khasraw, M, Roviello, G, Murphy, C, Muscat, A, Ashley, D, Mukaro, V, West, L, Liao, Y, Chisanga, D, Shi, W, Collins, I, Baron-Hay, S, Patil, S, Lindeman, G, and Khasraw, M
Abstract: BACKGROUND: This study evaluated the feasibility of achieving high response rates in stage II or III breast cancer by tailoring neoadjuvant therapy using clinical and histopathological features and the Oncotype DX Breast Recurrence Score. Genomic determinants of response and resistance were also explored. PATIENTS AND OUTCOME MEASURES: Fifty-one patients were enrolled. The primary cohort comprised 40 patients: 15 human epidermal growth factor receptor type 2 (HER2)-amplified; 15 triple-negative (TNBC); and ten hormone receptor (HR)-positive, HER2-non-amplified tumours; with recurrence scores ≥25. Patients were treated with epirubicin and cyclophosphamide, followed by nab-paclitaxel, with the addition of trastuzumab if HER2-amplified. The primary endpoint was pathological complete response (pCR) in the breast. Pre- and post-treatment tumour samples underwent variant burden, gene and gene pathway, mutational signature profile and clonal evolution analyses. RESULTS: The pCR rates were: overall 55% (n = 22), HER2-amplified 80% (n = 12), triple-negative 46% (n = 7) and HR-positive, HER2-non-amplified 30% (n = 3). Grade 3 or 4 adverse events included febrile neutropenia (8%), neutropenia (18%), sensory neuropathy (5%), deranged transaminases (5%), fatigue (2%), diarrhoea (2%), and pneumothorax (2%). Molecular analyses demonstrated strong similarities between residual disease and matched primary tumour. ATM signalling pathway alterations and the presence of a COSMIC Signature 3 implied the majority of tumours contained some form of homologous repair deficiency. ATM pathway alterations were identified in the subset of TNBC patients who did not achieve pCR; Signature 3 was present in both pCR and non-pCR subgroups. Clonal evolution analyses demonstrated both persistence and emergence of chemoresistant clones. CONCLUSIONS: This treatment regime resulted in a high rate of pCR, demonstrating that tailored neoadjuvant therapy using a genomic recurrence score is feasible and warr
Published: 2019

21. Oxaliplatin (Eloxatin)

Author: Baron-Hay, S
Published: 2001

22. Updated results of activity of durvalumab in advanced endometrial cancer (AEC) according to mismatch repair (MMR) status: The phase II PHAEDRA trial (ANZGOG1601)

Author: Antill, Y., primary, Kok, P.S., additional, Stockler, M.R., additional, Robledo, K., additional, Yip, S., additional, Parry, M., additional, Smith, D., additional, Spurdle, A., additional, Barnes, E., additional, Friedlander, M.L., additional, Baron-Hay, S., additional, Shannon, C., additional, Coward, J., additional, Beale, P.J., additional, Goss, G., additional, Meniawy, T., additional, Andrews, J., additional, Kelly, M., additional, and Mileshkin, L., additional
Published: 2019
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23. Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma.

Author: Jones M., Ferguson K., Martin K., Martyn A., Ranieri B., White J., Jayde V., Mamers P., Bowes L., Giles D., Hendley J., Schmidt T., Shirley H., Ball C., Young C., Viduka S., Tran H., Bilic S., Glavinas L., Brooks J., Stuart-Harris R., Kirsten F., Rutovitz J., Brand A., Byth K., Jaworski R., Harnett P., Sharma R., Wain G., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., deFazio A., McNeish I.A., Bowtell D.D., Swisher E.M., Dobrovic A., Wakefield M.J., Scott C.L., Bell R., Jobling T., Kondrashova O., Topp M., Nesic K., Lieschke E., Ho G.-Y., Harrell M.I., Zapparoli G.V., Hadley A., Holian R., Boehm E., Heong V., Sanij E., Pearson R.B., Krais J.J., Johnson N., McNally O., Ananda S., Alsop K., Hutt K.J., Kaufmann S.H., Lin K.K., Harding T.C., Traficante N., Chenevix-Trench G., Green A., Webb P., Gertig D., Fereday S., Moore S., Hung J., Harrap K., Sadkowsky T., Pandeya N., Malt M., Mellon A., Robertson R., VandenBergh T., Mackenzie P., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Galletta L., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., Links M., Grygiel J., Hill J., Jones M., Ferguson K., Martin K., Martyn A., Ranieri B., White J., Jayde V., Mamers P., Bowes L., Giles D., Hendley J., Schmidt T., Shirley H., Ball C., Young C., Viduka S., Tran H., Bilic S., Glavinas L., Brooks J., Stuart-Harris R., Kirsten F., Rutovitz J., Brand A., Byth K., Jaworski R., Harnett P., Sharma R., Wain G., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Phillips K., Rischin D., Fox S., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray W., Waring P., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Buck M., Haviv I., Purdie D., Whiteman D., Zeps N., deFazio A., McNeish I.A., Bowtell D.D., Swisher E.M., Dobrovic A., Wakefield M.J., Scott C.L., Bell R., Jobling T., Kondrashova O., Topp M., Nesic K., Lieschke E., Ho G.-Y., Harrell M.I., Zapparoli G.V., Hadley A., Holian R., Boehm E., Heong V., Sanij E., Pearson R.B., Krais J.J., Johnson N., McNally O., Ananda S., Alsop K., Hutt K.J., Kaufmann S.H., Lin K.K., Harding T.C., Traficante N., Chenevix-Trench G., Green A., Webb P., Gertig D., Fereday S., Moore S., Hung J., Harrap K., Sadkowsky T., Pandeya N., Malt M., Mellon A., Robertson R., VandenBergh T., Mackenzie P., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Galletta L., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., Links M., Grygiel J., and Hill J.
Abstract: Accurately identifying patients with high-grade serous ovarian carcinoma (HGSOC) who respond to poly(ADP-ribose) polymerase inhibitor (PARPi) therapy is of great clinical importance. Here we show that quantitative BRCA1 methylation analysis provides new insight into PARPi response in preclinical models and ovarian cancer patients. The response of 12 HGSOC patient-derived xenografts (PDX) to the PARPi rucaparib was assessed, with variable dose-dependent responses observed in chemo-naive BRCA1/2-mutated PDX, and no responses in PDX lacking DNA repair pathway defects. Among BRCA1-methylated PDX, silencing of all BRCA1 copies predicts rucaparib response, whilst heterozygous methylation is associated with resistance. Analysis of 21 BRCA1-methylated platinum-sensitive recurrent HGSOC (ARIEL2 Part 1 trial) confirmed that homozygous or hemizygous BRCA1 methylation predicts rucaparib clinical response, and that methylation loss can occur after exposure to chemotherapy. Accordingly, quantitative BRCA1 methylation analysis in a pre-treatment biopsy could allow identification of patients most likely to benefit, and facilitate tailoring of PARPi therapy.Copyright © 2018, The Author(s).
Published: 2018

24. Evaluating the role of magnetic resonance imaging post-neoadjuvant therapy for breast cancer in the NEONAB trial

Author: Murphy, C, Mukaro, V, Tobler, R, Asher, R, Gibbs, E, West, L, Giuffre, B, Baron-Hay, S, Khasraw, M, Murphy, C, Mukaro, V, Tobler, R, Asher, R, Gibbs, E, West, L, Giuffre, B, Baron-Hay, S, and Khasraw, M
Abstract: BACKGROUND: Magnetic resonance imaging (MRI) accuracy after neoadjuvant systemic therapy (NST) for breast cancer varies according to hormone receptor (HR), human epidermal growth factor receptor type-2 (HER2) subtype and Ki-67 proliferation index. Whether MRI accuracy varies by genomic signatures is unknown. We examined the accuracy of MRI in the NEONAB trial (Clinicaltrials.gov #: NCT01830244). AIM: To examine the accuracy of MRI to predict pathological response to neoadjuvant therapy for breast cancer in the NEONAB trial. METHODS: Patients with stages II-III breast cancer received sequential epirubicin, cyclophosphamide and nab-paclitaxel and trastuzumab if they were HER2+. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated to assess the utility of preoperative MRI to predict pathological complete response (pCR). Bland-Altman plots were used to assess agreement between MRI and pathological assessment of residual disease. RESULTS: MRI correctly predicted pCR in 64.1% of the cohort. Sensitivity and specificity were 52% and 78%, respectively; PPV 73% and NPV 58%. MRI predicted pCR most accurately in HER2-positive patients; sensitivity 58%, specificity 100%, PPV 100% and NPV 38%. MRI had higher PPV and NPV in tumours with Ki-67 ≥ 15% than tumours with Ki-67 < 15%, 75% versus 50% and 57.5% versus 50%, respectively. In this study, MRI underestimated residual tumour size by 1.65 mm (limits of agreement: 43.07-39.77 mm). CONCLUSIONS: MRI appears more accurate for predicting pCR in HER2+ disease than other subtypes and in cancers with Ki-67 ≥ 15% compared to those with Ki-67 < 15%. Accuracy of MRI in our HR+, RS ≥ 25 cohort is comparable to previous reports of unselected HR+ disease. MRI post-NST should be interpreted in conjunction with HER2 status and Ki-67 index of the primary.
Published: 2018

25. Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma

Author: Kondrashova, O, Topp, M, Nesic, K, Lieschke, E, Ho, G-Y, Harrell, M, Zapparoli, G, Hadley, A, Holian, R, Boehm, E, Heong, V, Sanij, E, Pearson, RB, Krais, JJ, Johnson, N, McNally, O, Ananda, S, Alsop, K, Hutt, KJ, Kaufmann, SH, Lin, KK, Harding, TC, Traficante, N, deFazio, A, McNeish, LA, Bowtell, DD, Swisher, EM, Dobrovic, A, Wakefield, MJ, Scott, CL, Chenevix-Trench, G, Green, A, Webb, P, Gertig, D, Fereday, S, Moore, S, Hung, J, Harrap, K, Sadkowsky, T, Pandeya, N, Malt, M, Mellon, A, Robertson, R, Vanden Bergh, T, Jones, M, Mackenzie, P, Maidens, J, Nattress, K, Chiew, YE, Stenlake, A, Sullivan, H, Alexander, B, Ashover, P, Brown, S, Corrish, T, Green, L, Jackman, L, Ferguson, K, Martin, K, Martyn, A, Ranieri, B, White, J, Jayde, V, Mamers, P, Bowes, L, Galletta, L, Giles, D, Hendley, J, Schmidt, T, Shirley, H, Ball, C, Young, C, Viduka, S, Tran, H, Bilic, S, Glavinas, L, Brooks, J, Stuart-Harris, R, Kirsten, F, Rutovitz, J, Clingan, P, Glasgow, A, Proietto, A, Braye, S, Otton, G, Shannon, J, Bonaventura, T, Stewart, J, Begbie, S, Friedlander, M, Bell, D, Baron-Hay, S, Ferrier, A, Gard, G, Nevell, D, Pavlakis, N, Valmadre, S, Young, B, Camaris, C, Crouch, R, Edwards, L, Hacker, N, Marsden, D, Robertson, G, Beale, P, Beith, J, Carter, J, Dalrymple, C, Houghton, R, Russell, P, Links, M, Grygiel, J, Hill, J, Brand, A, Byth, K, Jaworski, R, Harnett, P, Sharma, R, Wain, G, Ward, B, Papadimos, D, Crandon, A, Cummings, M, Horwood, K, Obermair, A, Perrin, L, Wyld, D, Nicklin, J, Davy, M, Oehler, MK, Hall, C, Dodd, T, Healy, T, Pittman, K, Henderson, D, Miller, J, Pierdes, J, Blomfield, P, Challis, D, Mclntosh, R, Parker, A, Brown, B, Rome, R, Allen, D, Grant, P, Hyde, S, Laurie, R, Robbie, M, Healy, D, Jobling, T, Manolitsas, T, McNealage, J, Rogers, P, Susil, B, Sumithran, E, Simpson, I, Phillips, K, Rischin, D, Fox, S, Johnson, D, Lade, S, Loughrey, M, O'Callaghan, N, Murray, W, Waring, P, Billson, V, Pyman, J, Neesham, D, Quinn, M, Underhill, C, Bell, R, Ng, LF, Blum, R, Ganju, V, Hammond, I, Leung, Y, McCartney, A, Buck, M, Haviv, I, Purdie, D, Whiteman, D, Zeps, N, Kondrashova, O, Topp, M, Nesic, K, Lieschke, E, Ho, G-Y, Harrell, M, Zapparoli, G, Hadley, A, Holian, R, Boehm, E, Heong, V, Sanij, E, Pearson, RB, Krais, JJ, Johnson, N, McNally, O, Ananda, S, Alsop, K, Hutt, KJ, Kaufmann, SH, Lin, KK, Harding, TC, Traficante, N, deFazio, A, McNeish, LA, Bowtell, DD, Swisher, EM, Dobrovic, A, Wakefield, MJ, Scott, CL, Chenevix-Trench, G, Green, A, Webb, P, Gertig, D, Fereday, S, Moore, S, Hung, J, Harrap, K, Sadkowsky, T, Pandeya, N, Malt, M, Mellon, A, Robertson, R, Vanden Bergh, T, Jones, M, Mackenzie, P, Maidens, J, Nattress, K, Chiew, YE, Stenlake, A, Sullivan, H, Alexander, B, Ashover, P, Brown, S, Corrish, T, Green, L, Jackman, L, Ferguson, K, Martin, K, Martyn, A, Ranieri, B, White, J, Jayde, V, Mamers, P, Bowes, L, Galletta, L, Giles, D, Hendley, J, Schmidt, T, Shirley, H, Ball, C, Young, C, Viduka, S, Tran, H, Bilic, S, Glavinas, L, Brooks, J, Stuart-Harris, R, Kirsten, F, Rutovitz, J, Clingan, P, Glasgow, A, Proietto, A, Braye, S, Otton, G, Shannon, J, Bonaventura, T, Stewart, J, Begbie, S, Friedlander, M, Bell, D, Baron-Hay, S, Ferrier, A, Gard, G, Nevell, D, Pavlakis, N, Valmadre, S, Young, B, Camaris, C, Crouch, R, Edwards, L, Hacker, N, Marsden, D, Robertson, G, Beale, P, Beith, J, Carter, J, Dalrymple, C, Houghton, R, Russell, P, Links, M, Grygiel, J, Hill, J, Brand, A, Byth, K, Jaworski, R, Harnett, P, Sharma, R, Wain, G, Ward, B, Papadimos, D, Crandon, A, Cummings, M, Horwood, K, Obermair, A, Perrin, L, Wyld, D, Nicklin, J, Davy, M, Oehler, MK, Hall, C, Dodd, T, Healy, T, Pittman, K, Henderson, D, Miller, J, Pierdes, J, Blomfield, P, Challis, D, Mclntosh, R, Parker, A, Brown, B, Rome, R, Allen, D, Grant, P, Hyde, S, Laurie, R, Robbie, M, Healy, D, Jobling, T, Manolitsas, T, McNealage, J, Rogers, P, Susil, B, Sumithran, E, Simpson, I, Phillips, K, Rischin, D, Fox, S, Johnson, D, Lade, S, Loughrey, M, O'Callaghan, N, Murray, W, Waring, P, Billson, V, Pyman, J, Neesham, D, Quinn, M, Underhill, C, Bell, R, Ng, LF, Blum, R, Ganju, V, Hammond, I, Leung, Y, McCartney, A, Buck, M, Haviv, I, Purdie, D, Whiteman, D, and Zeps, N
Abstract: Accurately identifying patients with high-grade serous ovarian carcinoma (HGSOC) who respond to poly(ADP-ribose) polymerase inhibitor (PARPi) therapy is of great clinical importance. Here we show that quantitative BRCA1 methylation analysis provides new insight into PARPi response in preclinical models and ovarian cancer patients. The response of 12 HGSOC patient-derived xenografts (PDX) to the PARPi rucaparib was assessed, with variable dose-dependent responses observed in chemo-naive BRCA1/2-mutated PDX, and no responses in PDX lacking DNA repair pathway defects. Among BRCA1-methylated PDX, silencing of all BRCA1 copies predicts rucaparib response, whilst heterozygous methylation is associated with resistance. Analysis of 21 BRCA1-methylated platinum-sensitive recurrent HGSOC (ARIEL2 Part 1 trial) confirmed that homozygous or hemizygous BRCA1 methylation predicts rucaparib clinical response, and that methylation loss can occur after exposure to chemotherapy. Accordingly, quantitative BRCA1 methylation analysis in a pre-treatment biopsy could allow identification of patients most likely to benefit, and facilitate tailoring of PARPi therapy.
Published: 2018

26. Life threatening laryngeal toxicity following treatment with combined chemoradiotherapy for nasopharyngeal cancer: A case report with review of the literature

Author: Baron-Hay, S., Clifford, A., Jackson, M., and Clarke, S.
Published: 1999
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27. Neurophysiological and clinical outcomes in chemotherapy-induced neuropathy in cancer

Author: Kandula, T, Farrar, MA, Kiernan, MC, Krishnan, AV, Goldstein, D, Horvath, L, Grimison, P, Boyle, F, Baron-Hay, S, Park, SB, Kandula, T, Farrar, MA, Kiernan, MC, Krishnan, AV, Goldstein, D, Horvath, L, Grimison, P, Boyle, F, Baron-Hay, S, and Park, SB
Abstract: Chemotherapy induced peripheral neuropathy (CIPN) is a significant toxicity of cancer treatment, with the potential to affect long-term function and quality of life in cancer survivors. There remains a lack of consensus around optimal assessment techniques. While current approaches to CIPN assessment are focused on clinical grading scales, it is becoming increasingly evident that a more comprehensive multimodal assessment package is necessary to accurately characterise the impact of CIPN as well as gauge the utility of neuroprotective mechanisms. Neurophysiological techniques provide objective biomarkers and may enable early detection of toxicity while patient reported outcomes are necessary to determine the significance of symptoms to individual patients. In addition to providing an objective assessment, clinical neurophysiological techniques provide important insights into the contributory pathophysiological mechanisms of CIPN with different chemotherapy agents. There is a paucity of implementation of these techniques in the clinical trial setting. The present Review aims to facilitate the use of neurophysiological studies as part of comprehensive assessment packages for the monitoring of CIPN by summarising current understanding of neurophysiological changes that underlie the development of neuropathy, clinical presentations and patient reported outcomes as well as advantages and limitations of current techniques for the neurophysiological assessment of CIPN.
Published: 2017

28. RAD51B in familial breast cancer.

Author: Antill Y., Garcia-Closas M., Michailidou K., Links M., Grygiel J., Hill J., Brand A., Byth K., Jaworski R., Harnett P., Wain G., Purdie D., Whiteman D., Ward B., Papadimos D., Crandon A., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy S.A.-M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Achan A., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Haviv I., Rischin D., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray B., Mileshkin L., Allan P., Billson V., Pyman J., Neesham D., Quinn M., Hamilton A., McNally O., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Stewart C., Zeps N., Bell R., Harris M., Healey S., Jobling T., Jones A., Wilson J., Pelttari L.M., Khan S., Vuorela M., Kiiski J.I., Vilske S., Nevanlinna V., Ranta S., Schleutker J., Winqvist R., Kallioniemi A., Dork T., Bogdanova N.V., Figueroa J., Pharoah P.D.P., Schmidt M.K., Dunning A.M., Bolla M.K., Dennis J., Wang Q., Hopper J.L., Southey M.C., Rosenberg E.H., Fasching P.A., Beckmann M.W., Peto J., Dos-Santos-silva I., Sawyer E.J., Tomlinson I., Burwinkel B., Surowy H., Guenel P., Truong T., Bojesen S.E., Nordestgaard B.G., Benitez J., Gonzalez-Neira A., Neuhausen S.L., Anton-Culver H., Brenner H., Arndt V., Meindl A., Schmutzler R.K., Brauch H., Bruning T., Lindblom A., Margolin S., Mannermaa A., Hartikainen J.M., Chenevix-Trench G., Van Dyck L., Janssen H., Chang-Claude J., Rudolph A., Radice P., Peterlongo P., Hallberg E., Olson J.E., Giles G.G., Milne R.L., Haiman C.A., Schumacher F., Simard J., Dumont M., Kristensen V., Borresen-Dale A.-L., Zheng W., Beeghly-Fadiel A., Grip M., Andrulis I.L., Glendon G., Devilee P., Seynaeve C., Hooning M.J., Collee M., Cox A., Cross S.S., Shah M., Luben R.N., Hamann U., Torres D., Jakubowska A., Lubinski J., Couch F.J., Yannoukakos D., Orr N., Swerdlow A., Darabi H., Li J., Czene K., Hall P., Easton D.F., Mattson J., Blomqvist C., Aittomaki K., Nevanlinna H., Aghmesheh M., Amor D., Andrews L., Armitage S., Arnold L., Balleine R., Bankier A., Bastick P., Beesley J., Beilby J., Bennett B., Bennett I., Berry G., Blackburn A., Bogwitz M., Brennan M., Brown M., Buckley M., Burgess M., Burke J., Butow P., Byron K., Callen D., Campbell I., Chauhan D., Christian A., Clarke C., Colley A., Cotton D., Crook A., Cui J., Culling B., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dickson R., Dixon J., Dobrovic A., Dudding T., Edkins T., Edwards S., Eisenbruch M., Farshid G., Fawcett S., Fellows A., Fenton G., Field M., Firgaira F., Flanagan J., Fleming J., Fong P., Forbes J., Fox S., French J., Friedlander M., Gaff C., Gardner M., Gattas M., George P., Gill G., Goldblatt J., Greening S., Grist S., Haan E., Hardie K., Hart S., Hayward N., Heiniger L., Humphrey E., Hunt C., James P., Jenkins M., Kefford R., Kidd A., Kiely B., Kirk J., Koehler J., Kollias J., Kovalenko S., Lakhani S., Leaming A., Leary J., Lim J., Lindeman G., Lipton L., Lobb L., Mann G., Marsh D., McLachlan S.A., Meiser B., Meldrum C., Mitchell G., Newman B., Nightingale S., O'Connell S., O'Loughlin I., Osborne R., Pachter N., Patterson B., Peters L., Phillips K., Price M., Purser L., Reeve T., Reeve J., Richards R., Rickard E., Robinson B., Rudzki B., Saleh M., Salisbury E., Sambrook J., Saunders C., Saunus J., Sayer R., Scott E., Scott R., Scott C., Seshadri R., Sexton A., Sharma R., Shelling A., Simpson P., Spurdle A., Suthers G., Sykes P., Taylor D., Taylor J., Thierry B., Thompson E., Thorne H., Townshend S., Trainer A., Tran L., Tucker K., Tyler J., Visvader J., Walker L., Walpole I., Ward R., Waring P., Warner B., Warren G., Williams R., Winship I., Wu K., Young M.A., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., Anderson L., Antill Y., Garcia-Closas M., Michailidou K., Links M., Grygiel J., Hill J., Brand A., Byth K., Jaworski R., Harnett P., Wain G., Purdie D., Whiteman D., Ward B., Papadimos D., Crandon A., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy S.A.-M., Oehler M.K., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Achan A., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Haviv I., Rischin D., Johnson D., Lade S., Loughrey M., O'Callaghan N., Murray B., Mileshkin L., Allan P., Billson V., Pyman J., Neesham D., Quinn M., Hamilton A., McNally O., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., Leung Y., McCartney A., Stewart C., Zeps N., Bell R., Harris M., Healey S., Jobling T., Jones A., Wilson J., Pelttari L.M., Khan S., Vuorela M., Kiiski J.I., Vilske S., Nevanlinna V., Ranta S., Schleutker J., Winqvist R., Kallioniemi A., Dork T., Bogdanova N.V., Figueroa J., Pharoah P.D.P., Schmidt M.K., Dunning A.M., Bolla M.K., Dennis J., Wang Q., Hopper J.L., Southey M.C., Rosenberg E.H., Fasching P.A., Beckmann M.W., Peto J., Dos-Santos-silva I., Sawyer E.J., Tomlinson I., Burwinkel B., Surowy H., Guenel P., Truong T., Bojesen S.E., Nordestgaard B.G., Benitez J., Gonzalez-Neira A., Neuhausen S.L., Anton-Culver H., Brenner H., Arndt V., Meindl A., Schmutzler R.K., Brauch H., Bruning T., Lindblom A., Margolin S., Mannermaa A., Hartikainen J.M., Chenevix-Trench G., Van Dyck L., Janssen H., Chang-Claude J., Rudolph A., Radice P., Peterlongo P., Hallberg E., Olson J.E., Giles G.G., Milne R.L., Haiman C.A., Schumacher F., Simard J., Dumont M., Kristensen V., Borresen-Dale A.-L., Zheng W., Beeghly-Fadiel A., Grip M., Andrulis I.L., Glendon G., Devilee P., Seynaeve C., Hooning M.J., Collee M., Cox A., Cross S.S., Shah M., Luben R.N., Hamann U., Torres D., Jakubowska A., Lubinski J., Couch F.J., Yannoukakos D., Orr N., Swerdlow A., Darabi H., Li J., Czene K., Hall P., Easton D.F., Mattson J., Blomqvist C., Aittomaki K., Nevanlinna H., Aghmesheh M., Amor D., Andrews L., Armitage S., Arnold L., Balleine R., Bankier A., Bastick P., Beesley J., Beilby J., Bennett B., Bennett I., Berry G., Blackburn A., Bogwitz M., Brennan M., Brown M., Buckley M., Burgess M., Burke J., Butow P., Byron K., Callen D., Campbell I., Chauhan D., Christian A., Clarke C., Colley A., Cotton D., Crook A., Cui J., Culling B., Cummings M., Dawson S.-J., DeFazio A., Delatycki M., Dickson R., Dixon J., Dobrovic A., Dudding T., Edkins T., Edwards S., Eisenbruch M., Farshid G., Fawcett S., Fellows A., Fenton G., Field M., Firgaira F., Flanagan J., Fleming J., Fong P., Forbes J., Fox S., French J., Friedlander M., Gaff C., Gardner M., Gattas M., George P., Gill G., Goldblatt J., Greening S., Grist S., Haan E., Hardie K., Hart S., Hayward N., Heiniger L., Humphrey E., Hunt C., James P., Jenkins M., Kefford R., Kidd A., Kiely B., Kirk J., Koehler J., Kollias J., Kovalenko S., Lakhani S., Leaming A., Leary J., Lim J., Lindeman G., Lipton L., Lobb L., Mann G., Marsh D., McLachlan S.A., Meiser B., Meldrum C., Mitchell G., Newman B., Nightingale S., O'Connell S., O'Loughlin I., Osborne R., Pachter N., Patterson B., Peters L., Phillips K., Price M., Purser L., Reeve T., Reeve J., Richards R., Rickard E., Robinson B., Rudzki B., Saleh M., Salisbury E., Sambrook J., Saunders C., Saunus J., Sayer R., Scott E., Scott R., Scott C., Seshadri R., Sexton A., Sharma R., Shelling A., Simpson P., Spurdle A., Suthers G., Sykes P., Taylor D., Taylor J., Thierry B., Thompson E., Thorne H., Townshend S., Trainer A., Tran L., Tucker K., Tyler J., Visvader J., Walker L., Walpole I., Ward R., Waring P., Warner B., Warren G., Williams R., Winship I., Wu K., Young M.A., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Bonaventura T., Stewart J., Begbie S., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Valmadre S., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Houghton R., Russell P., and Anderson L.
Abstract: Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 x 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.
Published: 2017

29. Refined cut-off for TP53 immunohistochemistry improves prediction of TP53mutation status in ovarian mucinous tumors: implications for outcome analyses

Author: Kang, Eun Young, Cheasley, Dane, LePage, Cecile, Wakefield, Matthew J., da Cunha Torres, Michelle, Rowley, Simone, Salazar, Carolina, Xing, Zhongyue, Allan, Prue, Bowtell, David D.L., Mes-Masson, Anne-Marie, Provencher, Diane M., Rahimi, Kurosh, Kelemen, Linda E., Fasching, Peter A., Doherty, Jennifer A., Goodman, Marc T., Goode, Ellen L., Deen, Suha, Pharoah, Paul D.P., Brenton, James D., Sieh, Weiva, Mateoiu, Constantina, Sundfeldt, Karin, Cook, Linda S., Le, Nhu D., Anglesio, Michael S., Gilks, C. Blake, Huntsman, David G., Kennedy, Catherine J., Traficante, Nadia, Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Bergh, T. Vanden, Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y.E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M.K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., O'Callaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L.F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., Zeps, N., DeFazio, Anna, Kaufmann, Scott, Churchman, Michael, Gourley, Charlie, Stephens, Andrew N., Meagher, Nicola S., Ramus, Susan J., Antill, Yoland C., Campbell, Ian, Scott, Clare L., Köbel, Martin, Gorringe, Kylie L., Cheasley, Dane, Wakefield, Matthew J., Ryland, Georgina L., Allan, Prue E., Alsop, Kathryn, Ananda, Sumitra, Anglesio, Michael S., Au-Yeung, George, Böhm, Maret, Bowtell, David D.L., Brand, Alison, Chenevix-Trench, Georgia, Christie, Michael, Chiew, Yoke-Eng, Churchman, Michael, DeFazio, Anna, Dudley, Rhiannon, Fairweather, Nicole, Fereday, Sian, Fox, Stephen B., Gilks, C. Blake, Gourley, Charlie, Hacker, Neville F., Hadley, Alison M., Hendley, Joy, Ho, Gwo-Yaw, Huntsman, David G., Hunter, Sally M., Jobling, Tom W., Kalli, Kimberly R., Kaufmann, Scott H., Kennedy, Catherine J., Köbel, Martin, Le Page, Cecile, McNally, Orla M., McAlpine, Jessica N., Mes-Masson, Anne-Marie, Mileshkin, Linda, Provencher, Diane M., Pyman, Jan, Rahimi, Kurosh, Samimi, Goli, Sharma, Ragwha, Stephens, Andrew N., Traficante, Nadia, Antill, Yoland C., Scott, Clare L., Campbell, Ian G., and Gorringe, Kylie L.
Abstract: TP53mutations are implicated in the progression of mucinous borderline tumors (MBOT) to mucinous ovarian carcinomas (MOC). Optimized immunohistochemistry (IHC) for TP53 has been established as a proxy for the TP53mutation status in other ovarian tumor types. We aimed to confirm the ability of TP53 IHC to predict TP53mutation status in ovarian mucinous tumors and to evaluate the association of TP53mutation status with survival among patients with MBOT and MOC. Tumor tissue from an initial cohort of 113 women with MBOT/MOC was stained with optimized IHC for TP53 using tissue microarrays (75.2%) or full sections (24.8%) and interpreted using established criteria as normal or abnormal (overexpression, complete absence, or cytoplasmic). Cases were considered concordant if abnormal IHC staining predicted deleterious TP53mutations. Discordant tissue microarray cases were re-evaluated on full sections and interpretational criteria were refined. The initial cohort was expanded to a total of 165 MBOT and 424 MOC for the examination of the association of survival with TP53mutation status, assessed either by TP53 IHC and/or sequencing. Initially, 82/113 (72.6%) cases were concordant using the established criteria. Refined criteria for overexpression to account for intratumoral heterogeneity and terminal differentiation improved concordance to 93.8% (106/113). In the expanded cohort, 19.4% (32/165) of MBOT showed evidence for TP53mutation and this was associated with a higher risk of recurrence, disease-specific death, and all-cause mortality (overall survival: HR = 4.6, 95% CI 1.5–14.3, p= 0.0087). Within MOC, 61.1% (259/424) harbored a TP53mutation, but this was not associated with survival (overall survival, p= 0.77). TP53 IHC is an accurate proxy for TP53mutation status with refined interpretation criteria accounting for intratumoral heterogeneity and terminal differentiation in ovarian mucinous tumors. TP53mutation status is an important biomarker to identify MBOT with a higher risk of mortality.
Published: 2021
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30. LBA12 - Updated results of activity of durvalumab in advanced endometrial cancer (AEC) according to mismatch repair (MMR) status: The phase II PHAEDRA trial (ANZGOG1601)

Author: Antill, Y., Kok, P.S., Stockler, M.R., Robledo, K., Yip, S., Parry, M., Smith, D., Spurdle, A., Barnes, E., Friedlander, M.L., Baron-Hay, S., Shannon, C., Coward, J., Beale, P.J., Goss, G., Meniawy, T., Andrews, J., Kelly, M., and Mileshkin, L.
Published: 2019
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31. Paclitaxel sensitivity in relation to ABCB1 expression, efflux and single nucleotide polymorphisms in ovarian cancer

Author: Gao, B, Russell, A, Beesley, J, Chen, XQ, Healey, S, Henderson, M, Wong, M, Emmanuel, C, Galletta, L, Johnatty, SE, Bowtell, D, Haber, M, Norris, M, Harnett, P, Chenevix-Trench, G, Balleine, RL, Defazio, A, Gertig, D, Green, A, Webb, P, Hung, J, Moore, S, Traficante, N, Fereday, S, Harrap, K, Sadkowsky, T, Pandeya, N, Stuart-Harris, R, Kirsten, F, Rutovitz, J, Clingan, P, Glasgow, A, Proietto, A, Braye, S, Otton, G, Shannon, J, Bonaventura, T, Stewart, J, Begbie, S, Friedlander, M, Bell, D, Baron-Hay, S, Ferrier, A, Gard, G, Nevell, D, Pavlakis, N, Valmadre, S, Young, B, Camaris, C, Crouch, R, Edwards, L, Hacker, N, Marsden, D, Robertson, G, Beale, P, Beith, J, Carter, J, Dalrymple, C, Hamilton, A, Houghton, R, Russell, P, Links, M, Grygiel, J, Hill, J, Brand, A, Byth, K, Jaworski, R, Sharma, R, Achen, A, Wain, G, Ward, B, Papadimos, D, Crandon, A, Cummings, M, Horwood, K, Obermair, A, Perrin, L, Wyld, D, Nicklin, J, Davy, M, Oehler, MK, Hall, C, Dodd, T, Healy, T, Pittman, K, Henderson, D, Miller, J, Pierdes, J, Blomfield, P, Challis, D, McIntosh, R, Parker, A, Brown, B, Rome, R, Allen, D, Grant, P, Hyde, S, Laurie, R, Robbie, M, Healy, D, Gao, B, Russell, A, Beesley, J, Chen, XQ, Healey, S, Henderson, M, Wong, M, Emmanuel, C, Galletta, L, Johnatty, SE, Bowtell, D, Haber, M, Norris, M, Harnett, P, Chenevix-Trench, G, Balleine, RL, Defazio, A, Gertig, D, Green, A, Webb, P, Hung, J, Moore, S, Traficante, N, Fereday, S, Harrap, K, Sadkowsky, T, Pandeya, N, Stuart-Harris, R, Kirsten, F, Rutovitz, J, Clingan, P, Glasgow, A, Proietto, A, Braye, S, Otton, G, Shannon, J, Bonaventura, T, Stewart, J, Begbie, S, Friedlander, M, Bell, D, Baron-Hay, S, Ferrier, A, Gard, G, Nevell, D, Pavlakis, N, Valmadre, S, Young, B, Camaris, C, Crouch, R, Edwards, L, Hacker, N, Marsden, D, Robertson, G, Beale, P, Beith, J, Carter, J, Dalrymple, C, Hamilton, A, Houghton, R, Russell, P, Links, M, Grygiel, J, Hill, J, Brand, A, Byth, K, Jaworski, R, Sharma, R, Achen, A, Wain, G, Ward, B, Papadimos, D, Crandon, A, Cummings, M, Horwood, K, Obermair, A, Perrin, L, Wyld, D, Nicklin, J, Davy, M, Oehler, MK, Hall, C, Dodd, T, Healy, T, Pittman, K, Henderson, D, Miller, J, Pierdes, J, Blomfield, P, Challis, D, McIntosh, R, Parker, A, Brown, B, Rome, R, Allen, D, Grant, P, Hyde, S, Laurie, R, Robbie, M, and Healy, D
Abstract: ABCB1 (adenosine triphosphate-binding cassette transporter B1) mediates cellular elimination of many chemotherapeutic agents including paclitaxel, which is commonly used to treat ovarian cancer. A significant association between common single nucleotide polymorphisms (SNPs) in ABCB1 and progression-free survival has been reported in patients with ovarian cancer. Variable paclitaxel clearance due to genotype specific differences in ABCB1 activity in cancer cells and/or normal tissues may underlie the association. Using cell-based models, we evaluated the correlations between ABCB1 expression, polymorphisms, transporter activity and paclitaxel sensitivity in ovarian cancer (n = 10) and lymphoblastoid (n = 19) cell lines. Close associations between ABCB1 expression, transporter function and paclitaxel sensitivity were found in lymphoblastoid cell lines, although we could not demonstrate an association with common SNPs. In ovarian cancer cell lines, ABCB1 expression was low and the association between expression and function was lost. These results suggest that ABCB1 related survival difference in ovarian cancer patients is more likely to be due to differential whole body paclitaxel clearance mediated by normal cells rather than a direct effect on cancer cells.
Published: 2014

32. Phase II, open-label trial of lapatinib and vinorelbine in women with previously treated HER2-positive metastatic breast cancer

Author: Chan, Arlene, Shannon, C., De Boer, R., Baron-Hay, S., Redfern, A., Bauwens, A., Craft, P., Webb, S., Townsend, A., Kotasek, D., Chan, Arlene, Shannon, C., De Boer, R., Baron-Hay, S., Redfern, A., Bauwens, A., Craft, P., Webb, S., Townsend, A., and Kotasek, D.
Abstract: Aim: To evaluate the efficacy and tolerability of lapatinib (L) and intravenous vinorelbine (V) in patients with metastatic HER2-positive breast cancer who have previously received two lines of anti-HER2 therapy (i.e. trastuzumab [T] with chemotherapy and lapatinib with capecitabine [LC]). Method: Consenting patients with measurable or evaluable disease and normal cardiac function who had progressed were recruited. Patients received LV (lapatinib 1250 mg orally daily, vinorelbine 20 mg/m2 intravenously on days 1 and 8 every 3 weeks) until progressive disease, intolerable toxicity or patient request. Results: The trial was closed early following inclusion of 19 patients due to slow accrual. Ten, five and four patients had received two, three and more than four lines of chemotherapy with T and LC, respectively, prior to study entry. Patients received a median of 5 cycles (range 1–18) of LV. Confirmed partial response was seen in 2 of 16 patients with measurable disease (12.5%); stable disease >24 weeks was seen in two patients (10.5%) with a clinical benefit rate of 20%. Fatigue and any grade neutropenia occurred commonly, but grade 4 severity occurred in only 5 and 11%, respectively. There were no episodes of cardiac dysfunction and no treatment-related deaths. The median progression-free survival was 3.9 months and overall survival (OS) was 9.1 months. Conclusion: The combination of LV demonstrated modest efficacy but was well tolerated. This combination may be of benefit to those patients who are unable to access the newer anti-HER2 agents and the low rate of treatment-emergent adverse effects will enable patients' symptoms, such as pain, to be minimized.
Published: 2014

33. Skewed X chromosome inactivation and breast and ovarian cancer status: Evidence for X-linked modifiers of BRCA1.

Author: Bonaventura T., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Links M., Grygiel J., Hill J., Brand A., Byth K., Jaworski R., Harnett P., Sharma R., Wain G., Purdie D., Whiteman D., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Haviv I., Phillips K., Rischin D., Fox S., Johnson D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., McCartney A., Leung Y., Buck M., Zeps N., Bell R., Jobling T., Tran H., Lose F., Duffy D.L., Kay G.F., Kedda M.A., Spurdle A.B., Bowtell D., Chenevix-Trench G., Green A., Webb P., DeFazio A., Gertig D., Traficante N., Moore S., Hung J., Fereday S., Harrap K., Sadkowsky T., Mellon A., Robertson R., Vanden Bergh T., Jones M., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes L., Mamers P., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Stewart J., Begbie S., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Young B., Camaris C., Bonaventura T., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Links M., Grygiel J., Hill J., Brand A., Byth K., Jaworski R., Harnett P., Sharma R., Wain G., Purdie D., Whiteman D., Ward B., Papadimos D., Crandon A., Cummings M., Horwood K., Obermair A., Perrin L., Wyld D., Nicklin J., Davy M., Oehler M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Healy D., Manolitsas T., McNealage J., Rogers P., Susil B., Sumithran E., Simpson I., Haviv I., Phillips K., Rischin D., Fox S., Johnson D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Pyman J., Neesham D., Quinn M., Underhill C., Ng L.F., Blum R., Ganju V., Hammond I., McCartney A., Leung Y., Buck M., Zeps N., Bell R., Jobling T., Tran H., Lose F., Duffy D.L., Kay G.F., Kedda M.A., Spurdle A.B., Bowtell D., Chenevix-Trench G., Green A., Webb P., DeFazio A., Gertig D., Traficante N., Moore S., Hung J., Fereday S., Harrap K., Sadkowsky T., Mellon A., Robertson R., Vanden Bergh T., Jones M., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes L., Mamers P., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Stuart-Harris R., Kirsten F., Rutovitz J., Clingan P., Glasgow A., Proietto A., Braye S., Otton G., Shannon J., Stewart J., Begbie S., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Pavlakis N., Young B., and Camaris C.
Abstract: Background: X chromosome inactivation, which silences gene expression from one of the two X chromosomes in females, is usually random. Skewed X inactivation has been implicated in both the expression and the suppression of X-linked disease phenotypes and has been reported to occur more frequently in breast and ovarian cancer patients, including BRCA1 or BRCA2 mutation carriers, than in control subjects. Method(s): We assessed the pattern of X chromosome inactivation using methylation-specific polymerase chain reaction amplification of the exon 1 microsatellite region of the X-linked androgen receptor (AR) gene in DNA from blood samples obtained from control subjects without a personal history of breast or ovarian cancer (n = 735), ovarian cancer patients (n = 313), familial breast cancer patients who did not carry mutations in BRCA1 or BRCA2 (n = 235), and affected and unaffected carriers of mutations in BRCA1 (n = 260) or BRCA2 (n = 63). We defined the pattern of X chromosome inactivation as skewed when the same X chromosome was active in at least 90% of cells. The association between skewed X inactivation and disease and/or BRCA mutation status was assessed by logistic regression analysis. The association between skewed X inactivation and age at cancer diagnosis was assessed by Cox proportional hazards regression analysis. All statistical tests were two-sided. Result(s): The age-adjusted frequency of skewed X inactivation was not statistically significantly higher in ovarian cancer or familial breast cancer case subjects compared with control subjects. Skewed X inactivation was higher in BRCA1 mutation carriers than in control subjects (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.1 to 6.2; P =. 02), particularly among unaffected women (OR = 6.1, 95% CI = 1.5 to 31.8; P =. 005). Among BRCA1 mutation carriers, those with skewed X inactivation were older at diagnosis of breast or ovarian cancer than those without skewed X inactivation (hazard ratio [HR] o
Published: 2012

34. Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium.

Author: Chenevix-Trench G., Gard G., Nevell D., Young B., Nattress K., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Perrin L., Ward B., Papadimos D., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Jayde V., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Traficante N., Fereday S., Bowes L., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Haviv I., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Jobling T., Tran H., Pearce C.L., Near A.M., Van Den Berg D.J., Ramus S.J., Gentry-Maharaj A., Menon U., Gayther S.A., Anderson A.R., Edlund C.K., Wu A.H., Chen X., Beesley J., Webb P., Holt S.K., Chen C., Doherty J.A., Rossing M.A., Whittemore A.S., McGuire V., DiCioccio R.A., Goodman M.T., Lurie G., Carney M.E., Wilkens L.R., Ness R.B., Moysich K.B., Edwards R., Jennison E., Kjaer S.K., Hogdall E., Hogdall C.K., Goode E.L., Sellers T.A., Vierkant R.A., Cunningham J.C., Schildkraut J.M., Berchuck A., Moorman P.G., Iversen E.S., Cramer D.W., Terry K.L., Vitonis A.F., Titus-Ernstoff L., Song H., Pharoah P.D.P., Spurdle A.B., Anton-Culver H., Ziogas A., Brewster W., Galitovskiy V., Gertig D., Vanden Bergh T., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., DeFazio A., Hung J., Chiew Y.E., Stenlake A., Sullivan H., Brand A., Jaworski R., Harnett P., Wain G., Green A., Moore S., Harrap K., Sadkowsky T., Purdie D., Whiteman D., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Mamers P., Healy D., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Zeps N., Mellon A., Robertson R., Proietto A., Braye S., Otton G., Bonaventura T., Stewart J., Friedlander M., Maidens J., Bell D., Baron-Hay S., Ferrier A., Chenevix-Trench G., Gard G., Nevell D., Young B., Nattress K., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Perrin L., Ward B., Papadimos D., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Miller J., Pierdes J., Jayde V., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Hyde S., Laurie R., Robbie M., Traficante N., Fereday S., Bowes L., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Haviv I., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Jobling T., Tran H., Pearce C.L., Near A.M., Van Den Berg D.J., Ramus S.J., Gentry-Maharaj A., Menon U., Gayther S.A., Anderson A.R., Edlund C.K., Wu A.H., Chen X., Beesley J., Webb P., Holt S.K., Chen C., Doherty J.A., Rossing M.A., Whittemore A.S., McGuire V., DiCioccio R.A., Goodman M.T., Lurie G., Carney M.E., Wilkens L.R., Ness R.B., Moysich K.B., Edwards R., Jennison E., Kjaer S.K., Hogdall E., Hogdall C.K., Goode E.L., Sellers T.A., Vierkant R.A., Cunningham J.C., Schildkraut J.M., Berchuck A., Moorman P.G., Iversen E.S., Cramer D.W., Terry K.L., Vitonis A.F., Titus-Ernstoff L., Song H., Pharoah P.D.P., Spurdle A.B., Anton-Culver H., Ziogas A., Brewster W., Galitovskiy V., Gertig D., Vanden Bergh T., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., DeFazio A., Hung J., Chiew Y.E., Stenlake A., Sullivan H., Brand A., Jaworski R., Harnett P., Wain G., Green A., Moore S., Harrap K., Sadkowsky T., Purdie D., Whiteman D., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Mamers P., Healy D., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Zeps N., Mellon A., Robertson R., Proietto A., Braye S., Otton G., Bonaventura T., Stewart J., Friedlander M., Maidens J., Bell D., Baron-Hay S., and Ferrier A.
Abstract: The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P<=0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: ORhomozygous(hom)=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, phet across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted. © 2009 Cancer Research UK.
Published: 2009

35. Immune thrombocytopenic purpura (ITP) and breast cancer. Does adjuvant therapy for breast cancer improve platelet counts in ITP?

Author: Khasraw, M., Baron-Hay, S., Khasraw, M., and Baron-Hay, S.
Abstract: Although both breast cancer and immune thrombocytopenic purpura (ITP) are common conditions, the simultaneous coexistence of these two diseases is rare. ITP is an autoimmune disease in which the presence of autoantibodies against platelets results in splenic sequestration and thrombocytopenia that may be associated with lymphoid neoplasms [1]. Except for an observational case series of 10 patients [2], only a few individual case reports of ITP coinciding with breast cancer have been reported [3–8]. We are reporting two cases with simultaneous confirmed ITP and breast cancer. The platelet counts in both women have improved during adjuvant breast cancer chemotherapy.
Published: 2009

36. Body size and risk of epithelial ovarian and related cancers: A population-based case-control study.

Author: Stewart J., Shirley H., Viduka S., Bilic S., Glavinas L., Proietto A., Braye S., Otton G., Bonaventura T., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Brand A., Jaworski R., Harnett P., Wain G., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Perrin L., Ward B., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Hyde S., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Laurie R., Robbie M., Healy D., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Haviv I., Zeps N., Parsons P.G., Hayward N., Jobling T., Tran H., Olsen C.M., Nagle C.M., Whiteman D., Purdie D., Green A.C., Webb P., Bowtell D., Chenevix-Trench G., Green A., DeFazio A., Gertig D., Traficante N., Moore S., Hung J., Fereday S., Harrap K., Sadkowsky T., Mellon A., Robertson R., Vanden Bergh T., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., CorrGreenish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes L., Mamers P., Schmidt T., Stewart J., Shirley H., Viduka S., Bilic S., Glavinas L., Proietto A., Braye S., Otton G., Bonaventura T., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Brand A., Jaworski R., Harnett P., Wain G., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Perrin L., Ward B., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Hyde S., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Laurie R., Robbie M., Healy D., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Haviv I., Zeps N., Parsons P.G., Hayward N., Jobling T., Tran H., Olsen C.M., Nagle C.M., Whiteman D., Purdie D., Green A.C., Webb P., Bowtell D., Chenevix-Trench G., Green A., DeFazio A., Gertig D., Traficante N., Moore S., Hung J., Fereday S., Harrap K., Sadkowsky T., Mellon A., Robertson R., Vanden Bergh T., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., CorrGreenish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes L., Mamers P., and Schmidt T.
Abstract: Different subtypes of ovarian cancer appear to have different causes; however, the association between body mass index (BMI) and the different subtypes is unclear. We examined the associations between body-mass index (BMI) and weight gain and risk of the different histological subtypes of epithelial ovarian cancer in a case-control study in Australia. Cases aged 18-79 with a new diagnosis of invasive epithelial ovarian cancer (n = 1,269) or borderline tumor (n = 311) were identified through a network of clinics and cancer registries throughout Australia. Controls (n = 1,509) were selected from the Electoral Roll. Height and weight (1 year previously, at age 20 and maximum weight) and other risk factor information were ascertained via a self-administered questionnaire. Obesity was positively associated with clear cell tumors (Odds Ratio 2.3; 95% confidence interval 1.2-4.2) but not invasive endometrioid or mucinous tumors. Although there was no association with invasive serous tumors overall (0.9; 0.7-1.2), we did see an increased risk of serous peritoneal tumors (2.9; 1.7-4.9), but not of serous tumors of the ovary and fallopian tube. Of the borderline subtypes, obesity was positively associated with serous (1.8; 1.1-2.8) but not mucinous tumors (1.1; 0.7-1.7). Overweight was not associated with any subtype overall. There was no association with BMI at age 20, or weight gain for any of the histological subtypes. These results add to the current evidence that obesity increases a woman's risk of developing distinct histological subtypes of ovarian cancer. © 2008 Wiley-Liss, Inc.
Published: 2008

37. Recreational physical activity and epithelial ovarian cancer: A case-control study, systematic review, and meta-analysis.

Author: Otton G., Bilic S., Glavinas L., Proietto A., Braye S., Hung J., Bonaventura T., Stewart J., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Brand A., Jaworski R., Harnett P., Wain G., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Perrin L., Ward B., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Hyde S., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Rome R., Allen D., Grant P., Laurie R., Robbie M., Healy D., Jobling T., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Haviv I., Purdie D., Zeps N., Parsons P.G., Hayward N., Olsen C.M., Bain C.J., Jordan S.J., Nagle C.M., Green A.C., Whiteman D., Webb P., Bowtell D., Chenevix-Trench G., Green A., Defazio A., Gertig D., Traficante N., Moore S., Fereday S., Harrap K., Sadkowsky T., Mellon A., Robertson R., Vanden Bergh T., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown B., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes L., Mamers P., Schmidt T., Shirley H., Viduka S., Tran H., Otton G., Bilic S., Glavinas L., Proietto A., Braye S., Hung J., Bonaventura T., Stewart J., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Brand A., Jaworski R., Harnett P., Wain G., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Perrin L., Ward B., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Hyde S., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Rome R., Allen D., Grant P., Laurie R., Robbie M., Healy D., Jobling T., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Haviv I., Purdie D., Zeps N., Parsons P.G., Hayward N., Olsen C.M., Bain C.J., Jordan S.J., Nagle C.M., Green A.C., Whiteman D., Webb P., Bowtell D., Chenevix-Trench G., Green A., Defazio A., Gertig D., Traficante N., Moore S., Fereday S., Harrap K., Sadkowsky T., Mellon A., Robertson R., Vanden Bergh T., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown B., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes L., Mamers P., Schmidt T., Shirley H., Viduka S., and Tran H.
Abstract: It remains unclear whether physical activity is associated with epithelial ovarian cancer risk. We therefore examined the association between recreational physical activity and risk of ovarian cancer in a national population-based case-control study in Australia. We also systematically reviewed all the available evidence linking physical activity with ovarian cancer to provide the best summary estimate of the association. The case-control study included women ages 18 to 79 years with a new diagnosis of invasive (n = 1,269) or borderline (n = 311) epithelial ovarian cancer identified through a network of clinics, physicians, and state cancer registries throughout Australia. Controls (n = 1,509) were randomly selected from the national electoral roll and were frequency matched to cases by age and state. For the systematic review, we identified eligible studies using Medline, the ISI Science Citation Index, and manual review of retrieved references, and included all case-control or cohort studies that permitted assessment of an association between physical activity (recreational/ occupational/sedentary behavior) and histologically confirmed ovarian cancer. Meta-analysis was restricted to the subset of these studies that reported on recreational physical activity. In our case-control study, we observed weakly inverse or null associations between recreational physical activity and risk of epithelial ovarian cancer overall. There was no evidence that the effects varied by tumor behavior or histologic subtype. Twelve studies were included in the meta-analysis, which gave summary estimates of 0.79 (95% confidence interval, 0.70-0.85) for case-control studies and 0.81 (95% confidence interval, 0.57-1.17) for cohort studies for the risk of ovarian cancer associated with highest versus lowest levels of recreational physical activity. Thus, pooled results fromobservational studies suggest that a modest inverse association exists between level of recreational physical activity a
Published: 2008

38. Consortium analysis of 7 candidate SNPs for ovarian cancer.

Author: Harrap K., Nevell D., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Brand A., Jaworski R., Harnett P., Wain G., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Papadimos D., Perrin L., Ward B., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Hyde S., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Laurie R., Robbie M., Healy D., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Haviv I., Purdie D., Whiteman D., Zeps N., Jobling T., Tran H., Ramus S.J., Vierkant R.A., Johnatty S.E., Pike M.C., Van Den Berg D.J., Wu A.H., Pearce C.L., Menon U., Gentry-Maharaj A., Gayther S.A., DiCioccio R.A., McGuire V., Whittemore A.S., Song H., Easton D.F., Pharoah P.D.P., Garcia-Closas M., Chanock S., Lissowska J., Brinton L., Terry K.L., Cramer D.W., Tworoger S.S., Hankinson S.E., Berchuck A., Moorman P.G., Schildkraut J.M., Cunningham J.M., Liebow M., Kjaer S.K., Hogdall E., Hogdall C., Blaakaer J., Ness R.B., Moysich K.B., Edwards R.P., Carney M.E., Lurie G., Goodman M.T., Wang-Gohrke S., Kropp S., Chang-Claude J., Webb P., Chen X., Beesley J., Chenevix-Trench G., Goode E.L., Bowtell D., Green A., DeFazio A., Gertig D., Traficante N., Moore S., Hung J., Fereday S., Sadkowsky T., Mellon A., Robertson R., Vanden Bergh T., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes V.L., Mamers P., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Proietto A., Braye S., Otton G., Bonaventura T., Stewart J., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Harrap K., Nevell D., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Brand A., Jaworski R., Harnett P., Wain G., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Papadimos D., Perrin L., Ward B., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Hyde S., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Laurie R., Robbie M., Healy D., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Haviv I., Purdie D., Whiteman D., Zeps N., Jobling T., Tran H., Ramus S.J., Vierkant R.A., Johnatty S.E., Pike M.C., Van Den Berg D.J., Wu A.H., Pearce C.L., Menon U., Gentry-Maharaj A., Gayther S.A., DiCioccio R.A., McGuire V., Whittemore A.S., Song H., Easton D.F., Pharoah P.D.P., Garcia-Closas M., Chanock S., Lissowska J., Brinton L., Terry K.L., Cramer D.W., Tworoger S.S., Hankinson S.E., Berchuck A., Moorman P.G., Schildkraut J.M., Cunningham J.M., Liebow M., Kjaer S.K., Hogdall E., Hogdall C., Blaakaer J., Ness R.B., Moysich K.B., Edwards R.P., Carney M.E., Lurie G., Goodman M.T., Wang-Gohrke S., Kropp S., Chang-Claude J., Webb P., Chen X., Beesley J., Chenevix-Trench G., Goode E.L., Bowtell D., Green A., DeFazio A., Gertig D., Traficante N., Moore S., Hung J., Fereday S., Sadkowsky T., Mellon A., Robertson R., Vanden Bergh T., Maidens J., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes V.L., Mamers P., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Proietto A., Braye S., Otton G., Bonaventura T., Stewart J., Friedlander M., Bell D., Baron-Hay S., Ferrier A., and Gard G.
Abstract: The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5' flanking CDKN2A, rs523349 in the 3' UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin. A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded [ordinal OR 1.10 (95% CI 1.01-1.20) p = 0.027; dominant OR 1.12 (95% CI 1.01-1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach. © 2008 Wiley-Liss, Inc.
Published: 2008

39. Talcum powder, chronic pelvic inflammation and NSAIDs in relation to risk of epithelial ovarian cancer.

Author: Proietto A., Vanden Bergh T., Maidens J., Brand A., Jaworski R., Harnett P., Wain G., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Perrin L., Ward B., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Hyde S., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Laurie R., Robbie M., Healy D., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Haviv I., Zeps N., Parsons P.G., Hayward N., Purdie D., Whiteman D., Jobling T., Tran H., Merritt M.A., Green A.C., Nagle C.M., Webb P.M., Bowtell D., Chenevix-Trench G., Green A., DeFazio A., Gertig D., Traficante N., Moore S., Hung J., Fereday S., Harrap K., Sadkowsky T., Mellon A., Robertson R., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes L., Mamers P., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Braye S., Otton G., Bonaventura T., Stewart J., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., Russell P., Proietto A., Vanden Bergh T., Maidens J., Brand A., Jaworski R., Harnett P., Wain G., Crandon A., Cummings M., Horwood K., Obermair A., Wyld D., Nicklin J., Perrin L., Ward B., Davy M., Hall C., Dodd T., Healy T., Pittman K., Henderson D., Hyde S., Miller J., Pierdes J., Blomfield P., Challis D., McIntosh R., Parker A., Brown B., Rome R., Allen D., Grant P., Laurie R., Robbie M., Healy D., Maniolitas T., McNealage J., Rogers P., Susil B., Veitch A., Constable J., Ping Tong S., Robinson I., Simpson I., Phillips K., Rischin D., Waring P., Loughrey M., O'Callaghan N., Murray B., Billson V., Galloway S., Pyman J., Quinn M., Hammond I., McCartney A., Leung Y., Haviv I., Zeps N., Parsons P.G., Hayward N., Purdie D., Whiteman D., Jobling T., Tran H., Merritt M.A., Green A.C., Nagle C.M., Webb P.M., Bowtell D., Chenevix-Trench G., Green A., DeFazio A., Gertig D., Traficante N., Moore S., Hung J., Fereday S., Harrap K., Sadkowsky T., Mellon A., Robertson R., Nattress K., Chiew Y.E., Stenlake A., Sullivan H., Alexander B., Ashover P., Brown S., Corrish T., Green L., Jackman L., Martin K., Ranieri B., White J., Jayde V., Bowes L., Mamers P., Schmidt T., Shirley H., Viduka S., Bilic S., Glavinas L., Braye S., Otton G., Bonaventura T., Stewart J., Friedlander M., Bell D., Baron-Hay S., Ferrier A., Gard G., Nevell D., Young B., Camaris C., Crouch R., Edwards L., Hacker N., Marsden D., Robertson G., Beale P., Beith J., Carter J., Dalrymple C., Hamilton A., Houghton R., and Russell P.
Abstract: Chronic inflammation has been proposed as the possible causal mechanism that explains the observed association between certain risk factors, such as the use of talcum powder (talc) in the pelvic region and epithelial ovarian cancer. To address this issue we evaluated the potential role of chronic local ovarian inflammation in the development of the major subtypes of epithelial ovarian cancer. Factors potentially linked to ovarian inflammation were examined in an Australia-wide case-control study comprising 1,576 women with invasive and low malignant potential (LMP) ovarian tumours and 1,509 population-based controls. We confirmed a statistically significant increase in ovarian cancer risk associated with use of talc in the pelvic region (adjusted odds ratio 1.17, 95% CI: 1.01-1.36) that was strongest for the serous and endometrioid subtypes although the latter was not statistically significant (adjusted odds ratios 1.21, 95% CI 1.03-1.44 and 1.18, 95% CI 0.81-1.70, respectively). Other factors potentially associated with ovarian inflammation (pelvic inflammatory disease, human papilloma virus infection and mumps) were not associated with risk but, like others, we found an increased risk of endometrioid and clear cell ovarian cancer only among women with a history of endometriosis. Regular use of aspirin and other nonsteroidal anti-inflammatory drugs was inversely associated with risk of LMP mucinous ovarian tumours only. We conclude that on balance chronic inflammation does not play a major role in the development of ovarian cancer. © 2007 Wiley-Liss, Inc.
Published: 2007

40. P5-22-01: Feasibility and Patient Safety of Serial Biopsies (bx) in Metastatic HER2−Positive Breast Cancer (BC) To Evaluate Alterations in Molecular Biomarkers (BM): Preliminary Results of SHERsig (Study of HER2 Signature in Metastatic Breast Cancer) a Prospective Phase II Study.

Author: Chan, A, primary, Chan, S, additional, Price, D, additional, Bergh, J, additional, Lluch, A, additional, Redfern, A, additional, Chirgwin, J, additional, Lidbrink, E, additional, Dhadda, A, additional, Lopéz-Vega, J, additional, Lindman, H, additional, Beith, J, additional, Baron-Hay, S, additional, Kiermaier, A, additional, Herbst, F, additional, and Ellis, I, additional
Published: 2011
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41. Low meprin expression differentiates primary ovarian mucinous carcinoma from gastrointestinal cancers that commonly metastasise to the ovaries

Author: Heinzelmann-Schwarz, V. A, primary, Scolyer, R. A, additional, Scurry, J. P, additional, Smith, A. N, additional, Gardiner-Garden, M., additional, Biankin, A. V, additional, Baron-Hay, S., additional, Scott, C., additional, Ward, R. L, additional, Fink, D., additional, Hacker, N. F, additional, Sutherland, R. L, additional, and O'Brien, P. M, additional
Published: 2007
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42. A distinct molecular profile associated with mucinous epithelial ovarian cancer

Author: Heinzelmann-Schwarz, V A, primary, Gardiner-Garden, M, additional, Henshall, S M, additional, Scurry, J P, additional, Scolyer, R A, additional, Smith, A N, additional, Bali, A, additional, Bergh, P Vanden, additional, Baron-Hay, S, additional, Scott, C, additional, Fink, D, additional, Hacker, N F, additional, Sutherland, R L, additional, and O'Brien, P M, additional
Published: 2006
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43. Small cell of the ovary, hypercalcemic type—Analysis of combined experience and recommendation for management. A GCIG study

Author: Harrison, M.L., primary, Hoskins, P., additional, du Bois, A., additional, Quinn, M., additional, Rustin, G.J.S., additional, Ledermann, J.A., additional, Baron-Hay, S., additional, and Friedlander, M.L., additional
Published: 2006
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44. Health-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician’s Choice

Author: Domenica Lorusso, Nicoletta Colombo, Antonio Casado Herraez, Alessandro D. Santin, Emeline Colomba, David Scott Miller, Keiichi Fujiwara, Sandro Pignata, Sally E. Baron-Hay, Isabelle Laure Ray-Coquard, Ronnie Shapira-Frommer, Yong Man Kim, Mary McCormack, Rachid Massaad, Allison Martin Nguyen, Qi Zhao, Jodi McKenzie, Vimalanand S. Prabhu, Vicky Makker, Lorusso, D, Colombo, N, Herraez, A, Santin, A, Colomba, E, Miller, D, Fujiwara, K, Pignata, S, Baron-Hay, S, Ray-Coquard, I, Shapira-Frommer, R, Kim, Y, Mccormack, M, Massaad, R, Nguyen, A, Zhao, Q, Mckenzie, J, Prabhu, V, and Makker, V
Subjects: Cancer Research, Endometrial cancer, Oncology, Health-related quality of life, Lenvatinib, Pembrolizumab, Patient-reported outcome
Abstract: Purpose: Lenvatinib and pembrolizumab (LEN+PEMBRO) demonstrated clinically meaningful and statistically significant improvements in efficacy versus treatment of physician's choice (TPC) in patients with advanced endometrial cancer (aEC) in the phase 3 Study 309/KEYNOTE-775. Health-related quality-of-life (HRQoL) is reported. Patients and Methods: Patients were randomly assigned to receive LEN+PEMBRO (n = 411; LEN 20 mg/day; PEMBRO 200 mg Q3W) or TPC (n = 416; doxorubicin 60 mg/m2 Q3W or paclitaxel 80 mg/m2 [weekly, 3 weeks on/1 week off]). Impact of treatment on HRQoL assessed by the global health status/quality of life (GHS/QoL) score of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) was a secondary objective; other scales of the Quality-of-Life Questionnaire (QLQ-C30), EORTC QLQ-Endometrial, 24 questions (EORTC QLQ-EN24), and EuroQoL 5 dimensions, 5 levels (EQ-5D-5L) were exploratory objectives. HRQoL was assessed on day 1 of each cycle. Completion/compliance, change from baseline, time to first and definitive deterioration were assessed. No multiplicity adjustments were applied for HRQoL endpoints. Results: The latest timepoint at which the predefined rates of completion (≥60%) and compliance (≥80%) were met was week 12. HRQoL at week 12 between treatment groups was generally similar. Time to first deterioration symptom scales favoured LEN+PEMBRO for QLQ-C30 dyspnoea, and QLQ-EN24 for poor body image, tingling/numbness, and hair loss; and TPC was favoured for QLQ-C30 pain, appetite loss, and diarrhoea, and QLQ-EN24 muscular pain. While the QLQ-C30 physical functional scale favoured TPC, other functional scales were generally similar between arms. Time to definitive deterioration favoured LEN+PEMBRO on most scales. Conclusion: HRQoL data from Study 309/KEYNOTE-775, with previously published efficacy and safety results, indicate that LEN+PEMBRO has an overall favourable benefit/risk profile versus TPC for the treatment of patients with aEC.
Published: 2023

45. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775

Author: Vicky Makker, Nicoletta Colombo, Antonio Casado Herráez, Bradley J. Monk, Helen Mackay, Alessandro D. Santin, David S. Miller, Richard G. Moore, Sally Baron-Hay, Isabelle Ray-Coquard, Kimio Ushijima, Kan Yonemori, Yong Man Kim, Eva M. Guerra Alia, Ulus A. Sanli, Steven Bird, Robert Orlowski, Jodi McKenzie, Chinyere Okpara, Gianmaria Barresi, Domenica Lorusso, Makker, V, Colombo, N, Herráez, A, Monk, B, Mackay, H, Santin, A, Miller, D, Moore, R, Baron-Hay, S, Ray-Coquard, I, Ushijima, K, Yonemori, K, Kim, Y, Guerra Alia, E, Sanli, U, Bird, S, Orlowski, R, Mckenzie, J, Okpara, C, Barresi, G, and Lorusso, D
Subjects: Cancer Research, Oncology, Endometrial Cancer
Abstract: Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We report the final prespecified analysis for overall survival (OS), along with updated progression-free survival (PFS) and objective response rate (ORR), and safety from the open-label, randomized, phase III Study 309/KEYNOTE-775. In total, 827 patients with advanced, recurrent, or metastatic endometrial cancer (EC) were randomly assigned to receive lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously once every 3 weeks (n = 411) or chemotherapy of the treating physician's choice (doxorubicin 60 mg/m2 intravenously once every 3 weeks or paclitaxel 80 mg/m2 intravenously once weekly [3 weeks on; 1 week off] [n = 416]). Efficacy was reported for patients with mismatch repair proficient (pMMR) tumors and all-comers, and by subgroups (histology, prior therapy, MMR status). Updated safety was also reported. Lenvatinib plus pembrolizumab showed benefits in OS (pMMR HR, 0.70; 95% CI, 0.58 to 0.83; all-comer HR, 0.65; 95% CI, 0.55 to 0.77), PFS (pMMR HR, 0.60; 95% CI, 0.50 to 0.72; all-comer HR, 0.56; 95% CI, 0.48 to 0.66), and ORR (pMMR patients, 32.4% v 15.1%; all-comers, 33.8% v 14.7%) versus chemotherapy. OS, PFS, and ORR favored lenvatinib plus pembrolizumab in all subgroups of interest. No new safety signals were observed. Lenvatinib plus pembrolizumab continued to show improved efficacy versus chemotherapy and manageable safety in patients with previously treated advanced EC.
Published: 2023

46. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer

Author: Vicky, Makker, Nicoletta, Colombo, Antonio, Casado Herráez, Alessandro D, Santin, Emeline, Colomba, David S, Miller, Keiichi, Fujiwara, Sandro, Pignata, Sally, Baron-Hay, Isabelle, Ray-Coquard, Ronnie, Shapira-Frommer, Kimio, Ushijima, Jun, Sakata, Kan, Yonemori, Yong Man, Kim, Eva M, Guerra, Ulus A, Sanli, Mary M, McCormack, Alan D, Smith, Stephen, Keefe, Steven, Bird, Lea, Dutta, Robert J, Orlowski, Domenica, Lorusso, Lynne, Knowles, Makker, V, Colombo, N, Casado Herráez, A, Santin, A, Colomba, E, Miller, D, Fujiwara, K, Pignata, S, Baron-Hay, S, Ray-Coquard, I, Shapira-Frommer, R, Ushijima, K, Sakata, J, Yonemori, K, Kim, Y, Guerra, E, Sanli, U, Mccormack, M, Smith, A, Keefe, S, Bird, S, Dutta, L, Orlowski, R, and Lorusso, D
Subjects: Adult, Efficacy, Antibodies, Monoclonal, Humanized, Trial, platinum-based chemotherapy remains unclear, Antineoplastic Combined Chemotherapy Protocols, Humans, Women, Phase-Ii, Multicenter, Aged, Aged, 80 and over, Phenylurea Compounds, Carcinoma, Obstetrics and Gynecology, General Medicine, Middle Aged, Survival Analysis, Endometrial Neoplasms, Settore MED/40 - GINECOLOGIA E OSTETRICIA, N/A, Combination, Quinolines, Female, Open-Label, Safety
Abstract: BACKGROUND Standard therapy for advanced endometrial cancer after failure of platinum-based chemotherapy remains unclear. METHODS In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with advanced endometrial cancer who had previously received at least one platinum-based chemotherapy regimen to receive either lenvatinib (20 mg, administered orally once daily) plus pembrolizumab (200 mg, administered intravenously every 3 weeks) or chemotherapy of the treating physician's choice (doxorubicin at 60 mg per square meter of body-surface area, administered intravenously every 3 weeks, or paclitaxel at 80 mg per square meter, administered intravenously weekly [with a cycle of 3 weeks on and 1 week off]). The two primary end points were progression-free survival as assessed on blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1, and overall survival. The end points were evaluated in patients with mismatch repair-proficient (pMMR) disease and in all patients. Safety was also assessed. RESULTS A total of 827 patients (697 with pMMR disease and 130 with mismatch repair-deficient disease) were randomly assigned to receive lenvatinib plus pembrolizumab (411 patients) or chemotherapy (416 patients). The median progression-free survival was longer with lenvatinib plus pembrolizumab than with chemotherapy (pMMR population: 6.6 vs. 3.8 months; hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.50 to 0.72; P, Eisai; Merck Sharp and Dohme, Supported by Eisai and Merck Sharp and Dohme, a subsidiary of Merck.
Published: 2022

47. Medicine Access Programmes: what do patients think - a patient-reported outcome study on ribociclib in metastatic breast cancer in Australia.

Author: Yap N, Wong V, Morton C, de Boer R, Baron-Hay S, Blum R, Forster B, Chua S, Clarke K, Cuff K, Green M, Lim E, Mok K, Nott L, Nottage M, Tafreshi A, Tsoi D, Uccellini A, Gibbs P, and Lok SW
Subjects: Humans, Female, Australia, Middle Aged, Aged, Adult, Medication Adherence, Health Services Accessibility, Antineoplastic Agents therapeutic use, Neoplasm Metastasis, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Patient Reported Outcome Measures, Purines therapeutic use, Aminopyridines therapeutic use
Abstract: This study evaluated patient-reported outcomes (PROs) of Medicine Access Programmes (MAPs) for Australian metastatic breast cancer patients on ribociclib. Limited patient awareness of MAP enrolment was identified, emphasising the need for improved education and consent processes. Most patients expressed gratitude for accessing non-funded medications and perceived enhanced medication adherence as a key benefit. Integrating PRO data with real-world registry data provides comprehensive insight for future MAP development., (© 2024 Royal Australasian College of Physicians.)
Published: 2024
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48. Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial.

Author: Harbeck N, Ciruelos E, Jerusalem G, Müller V, Niikura N, Viale G, Bartsch R, Kurzeder C, Higgins MJ, Connolly RM, Baron-Hay S, Gión M, Guarneri V, Bianchini G, Wildiers H, Escrivá-de-Romaní S, Prahladan M, Bridge H, Kuptsova-Clarkson N, Scotto N, Verma S, and Lin NU
Abstract: Trastuzumab deruxtecan (T-DXd) intracranial activity has been observed in small or retrospective patient cohorts with human epidermal growth factor receptor 2-positive (HER2 + ) advanced/metastatic breast cancer (mBC) and stable or active (untreated/previously treated and progressing) brain metastases (BMs). The phase 3b/4 DESTINY-Breast12 study investigated T-DXd in patients with HER2 + mBC and is, to our knowledge, the largest prospective study of T-DXd in patients with BMs in this setting. Patients (stable/active BMs (n = 263) and no BMs (n = 241)) treated with one or more prior anti-HER2-based regimens received T-DXd (5.4 mg per kg). Primary endpoints were progression-free survival (PFS; BMs cohort) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (non-BMs cohort). Additional endpoints included central nervous system (CNS) PFS, ORR, time to second progression, CNS ORR (BMs cohort), incidence of new symptomatic CNS metastases (non-BMs cohort), time to progression, duration of response, overall survival and safety (both cohorts). No formal hypothesis testing was conducted for this single-arm, open-label study. In the BMs cohort, 12-month PFS was 61.6% (95% confidence interval (CI): 54.9-67.6), and 12-month CNS PFS was 58.9% (95% CI: 51.9-65.3). In the non-BMs cohort, ORR was 62.7% (95% CI: 56.5-68.8). Grade 3 or higher adverse events occurred in 51% (BMs cohort) and 49% (non-BMs cohort) of patients. Investigator-reported interstitial lung disease/pneumonitis occurred in 16% (grade ≥3: 3%) of patients with BMs and 13% (grade ≥3: 1%) of patients without BMs. These data show substantial and durable overall and intracranial activity for T-DXd, supporting its use in previously treated patients with HER2 + mBC irrespective of stable/active baseline BMs. ClinicalTrials.gov identifier: NCT04739761 ., (© 2024. The Author(s).)
Published: 2024
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49. Validity of Patient-Reported Outcome Measures in Evaluating Nerve Damage Following Chemotherapy.

Author: Li T, Timmins HC, Mahfouz FM, Trinh T, Mizrahi D, Horvath LG, Harrison M, Grimison P, Friedlander M, Marx G, Boyle F, Wyld D, Henderson R, King T, Baron-Hay S, Kiernan MC, Rutherford C, Goldstein D, and Park SB
Subjects: Humans, Female, Male, Middle Aged, Cross-Sectional Studies, Aged, Australia, Neoplasms drug therapy, Reproducibility of Results, Quality of Life, Cohort Studies, Adult, Prospective Studies, Patient Reported Outcome Measures, Peripheral Nervous System Diseases chemically induced, Antineoplastic Agents adverse effects
Abstract: Importance: Chemotherapy-induced peripheral neuropathy (CIPN) is a substantial adverse effect of anticancer treatments. As such, the assessment of CIPN remains critically important in both research and clinic settings., Objective: To compare the validity of various patient-reported outcome measures (PROMs) with neurophysiological and sensory functional measures as the optimal method of CIPN assessment., Design, Setting, and Participants: This cohort study evaluated participants treated with neurotoxic chemotherapy across 2 cohorts using a dual-study design. Participants commencing treatment were assessed prospectively at beginning of neurotoxic treatment, midtreatment, and at the end of treatment. Participants who completed treatment up to 5 years prior were assessed cross-sectionally and completed a single assessment time point. Participants were recruited from oncology centers in Australia from August 2015 to November 2022. Data analysis occurred from February to November 2023., Exposures: Neurotoxic cancer treatment including taxanes, platinums, vinca-alkaloids, proteasome inhibitors, and thalidomide., Main Outcomes and Measures: CIPN was assessed via PROMs (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC-CIPN20], Functional Assessment of Cancer Therapy/Gynecological Cancer Group Neurotoxicity Questionnaire (FACT/GOG-Ntx), and the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events [PRO-CTCAE]), neurological and neurophysiological assessment (Total Neuropathy Score and sural and tibial compound nerve amplitudes), and sensory measures (Grating orientation, Von Frey monofilament, and 2-point discrimination tasks). Core measurement properties of CIPN outcome measures were evaluated. Convergent and known-groups validity was assessed cross-sectionally following treatment completion, and responsiveness was evaluated prospectively during treatment. Neurological, neurophysiological, and sensory outcome measure scores were compared between those who reported high and low levels of CIPN symptoms using linear regressions., Results: A total of 1033 participants (median [IQR] age, 61 [50-59] years; 676 female [65.4%]) were recruited to this study, incorporating 1623 assessments. PROMs demonstrated best ability to accurately assess CIPN (convergent validity), especially the PRO-CTCAE composite score (r = 0.85; P < .001) and EORTC-CIPN20 (r = 0.79; P < .001). PROMS also demonstrated the best ability to discriminate between CIPN severity (known-groups validity) and to detect changes at onset of CIPN development (responsiveness), especially for EORTC-CIPN20 (d = 0.67; 95% CI, 0.52-0.83), FACT/GOG-Ntx (d = 0.65; 95% CI, 0.49-0.81) and the PRO-CTCAE (d = 0.83; 95% CI, 0.64-1.02). Other measures did not achieve threshold for convergent validity (α < 0.7). Neurophysiological and sensory measures did not demonstrate acceptable responsiveness. In regression models, neurological, neurophysiological, and sensory outcome measures were significantly impaired in participants who reported high levels of CIPN symptoms compared with those who reported low levels of CIPN symptoms., Conclusions and Relevance: In this cohort study of 1033 cancer patients, PROMs were the only measures to satisfy all 3 core measurement property criteria (convergent validity, known-groups validity, and responsiveness). These findings suggest that adoption of PROMs in clinical practice can equip clinicians with valuable information in assessing CIPN morbidity.
Published: 2024
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50. Metastatic primary breast neuroendocrine neoplasms: a case series.

Author: Batty K, Taylor AM, Bernard EJ, Diakos CI, Clarke SJ, Guminski A, Baron-Hay S, Boyle F, Pavlakis N, and Chan DL
Subjects: Humans, Female, Adult, Middle Aged, Prognosis, Fluorodeoxyglucose F18, Retrospective Studies, Neuroendocrine Tumors diagnostic imaging, Neuroendocrine Tumors therapy, Breast Neoplasms diagnostic imaging, Breast Neoplasms therapy, Carcinoma, Neuroendocrine diagnostic imaging, Carcinoma, Neuroendocrine therapy, Neoplasms, Second Primary
Abstract: Background: Breast neuroendocrine neoplasms represent a rare subtype of breast cancer which have not been well studied or characterised, particularly in the metastatic setting., Aim: To present clinicopathological characteristics, treatment and outcomes of a series of patients with metastatic neuroendocrine carcinoma of the breast and review the current literature., Methods: We performed a retrospective review to identify and describe patients with metastatic neuroendocrine carcinoma of the breast at our centre between 2011 and 2021. Medical records, pathology and imaging results were examined to evaluate the clinical and histopathological features as well as the treatment pathways and prognosis of these patients., Results: We present a series of seven female patients with metastatic neuroendocrine carcinoma of the breast, as defined by the World Health Organization classification, over a period of 10 years (2011-2021) from a single centre. Median age at diagnosis was 48 years (range 39-63). Six of seven tissue samples expressed synaptophysin and chromogranin and were also oestrogen and progesterone receptor positive; median Ki-67 index was 50% (range 20-90%). All seven patients had demonstrated avidity on 18 F-FDG PET imaging, and the six who underwent 68 Ga-DOTATATE PET all had significant avidity. Treatment modalities and sequencing varied, but all patients received chemotherapy during their disease course. Six patients received three or more lines of treatment. Median overall survival was 31.8 months (range 3.7-108.6). Median progression-free survival (PFS) with first-line therapy for metastatic disease was 5.8 months (range 1.8-37.8)., Conclusions: This series shows the use of multiple modalities in treating this disease, with different sequencing in different patients. Despite multiple modalities used in the first-line setting, first-line PFS remains short. Larger series and further molecular characterisation are required to aid clinicians in managing this condition and to guide optimal treatment sequencing to improve outcomes in this rare patient group., (© 2022 Royal Australasian College of Physicians.)
Published: 2023
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