28 results on '"Piper, Tammy"'
Search Results
2. Systematically higher Ki67 scores on core biopsy samples compared to corresponding resection specimen in breast cancer: a multi-operator and multi-institutional study
- Author
-
Acs, Balazs, Leung, Samuel C. Y., Kidwell, Kelley M., Arun, Indu, Augulis, Renaldas, Badve, Sunil S., Bai, Yalai, Bane, Anita L., Bartlett, John M. S., Bayani, Jane, Bigras, Gilbert, Blank, Annika, Buikema, Henk, Chang, Martin C., Dietz, Robin L., Dodson, Andrew, Fineberg, Susan, Focke, Cornelia M., Gao, Dongxia, Gown, Allen M., Gutierrez, Carolina, Hartman, Johan, Kos, Zuzana, Lænkholm, Anne-Vibeke, Laurinavicius, Arvydas, Levenson, Richard M., Mahboubi-Ardakani, Rustin, Mastropasqua, Mauro G., Nofech-Mozes, Sharon, Osborne, C. Kent, Penault-Llorca, Frédérique M., Piper, Tammy, Quintayo, Mary Anne, Rau, Tilman T., Reinhard, Stefan, Robertson, Stephanie, Salgado, Roberto, Sugie, Tomoharu, van der Vegt, Bert, Viale, Giuseppe, Zabaglo, Lila A., Hayes, Daniel F., Dowsett, Mitch, Nielsen, Torsten O., and Rimm, David L.
- Published
- 2022
- Full Text
- View/download PDF
3. Correlative studies of the Breast Cancer Index (HOXB13/IL17BR) and ER, PR, AR, AR/ER ratio and Ki67 for prediction of extended endocrine therapy benefit: a Trans-aTTom study
- Author
-
Sgroi, Dennis C., Treuner, Kai, Zhang, Yi, Piper, Tammy, Salunga, Ranelle, Ahmed, Ikhlaaq, Doos, Lucy, Thornber, Sarah, Taylor, Karen J., Brachtel, Elena, Pirrie, Sarah, Schnabel, Catherine A., Rea, Daniel, and Bartlett, John M. S.
- Published
- 2022
- Full Text
- View/download PDF
4. Adjunctive Statistical Standardization of Adjuvant Estrogen Receptor and Progesterone Receptor in Canadian Cancer Trials Group MA.27 Postmenopausal Breast Cancer Trial of Exemestane Versus Anastrozole.
- Author
-
Chapman, Judith-Anne W., Bayani, Jane, SenGupta, Sandip, Bartlett, John M.S., Piper, Tammy, Quintayo, Mary Anne, Virk, Shakeel, Goss, Paul E., Ingle, James N., Ellis, Matthew J., Sledge, George W., Budd, G. Thomas, Rabaglio, Manuela, Ansari, Rafat H., Tozer, Richard, D'Souza, David P., Chalchal, Haji, Spadafora, Silvana, Stearns, Vered, and Perez, Edith A.
- Published
- 2024
- Full Text
- View/download PDF
5. Comparative survival analysis of multiparametric tests—when molecular tests disagree—A TEAM Pathology study
- Author
-
Bartlett, John M. S., Bayani, Jane, Kornaga, Elizabeth, Xu, Keying, Pond, Greg R., Piper, Tammy, Mallon, Elizabeth, Yao, Cindy Q., Boutros, Paul C., Hasenburg, Annette, Dunn, J. A., Markopoulos, Christos, Dirix, Luc, Seynaeve, Caroline, van de Velde, Cornelis J. H., Stein, Robert C., and Rea, Daniel
- Published
- 2021
- Full Text
- View/download PDF
6. Evaluation of multiple transcriptomic gene risk signatures in male breast cancer
- Author
-
Bayani, Jane, Poncet, Coralie, Crozier, Cheryl, Neven, Anouk, Piper, Tammy, Cunningham, Carrie, Sobol, Monika, Aebi, Stefan, Benstead, Kim, Bogler, Oliver, Dal Lago, Lissandra, Fraser, Judith, Hilbers, Florentine, Hedenfalk, Ingrid, Korde, Larissa, Linderholm, Barbro, Martens, John, Middleton, Lavinia, Murray, Melissa, Kelly, Catherine, Nilsson, Cecilia, Nowaczyk, Monika, Peeters, Stephanie, Peric, Aleksandra, Porter, Peggy, Schröder, Carolien, Rubio, Isabel T., Ruddy, Kathryn J., van Asperen, Christi, Van Den Weyngaert, Danielle, van Deurzen, Carolien, van Leeuwen-Stok, Elise, Vermeij, Joanna, Winer, Eric, Giordano, Sharon H., Cardoso, Fatima, and Bartlett, John M. S.
- Published
- 2021
- Full Text
- View/download PDF
7. An international multicenter study to evaluate reproducibility of automated scoring for assessment of Ki67 in breast cancer
- Author
-
Rimm, David L., Leung, Samuel C.Y., McShane, Lisa M., Bai, Yalai, Bane, Anita L., Bartlett, John M.S., Bayani, Jane, Chang, Martin C., Dean, Michelle, Denkert, Carsten, Enwere, Emeka K., Galderisi, Chad, Gholap, Abhi, Hugh, Judith C., Jadhav, Anagha, Kornaga, Elizabeth N., Laurinavicius, Arvydas, Levenson, Richard, Lima, Joema, Miller, Keith, Pantanowitz, Liron, Piper, Tammy, Ruan, Jason, Srinivasan, Malini, Virk, Shakeel, Wu, Ying, Yang, Hua, Hayes, Daniel F., Nielsen, Torsten O., and Dowsett, Mitch
- Published
- 2019
- Full Text
- View/download PDF
8. An international study to increase concordance in Ki67 scoring
- Author
-
Polley, Mei-Yin C, Leung, Samuel C Y, Gao, Dongxia, Mastropasqua, Mauro G, Zabaglo, Lila A, Bartlett, John M S, McShane, Lisa M, Enos, Rebecca A, Badve, Sunil S, Bane, Anita L, Borgquist, Signe, Fineberg, Susan, Lin, Ming-Gang, Gown, Allen M, Grabau, Dorthe, Gutierrez, Carolina, Hugh, Judith C, Moriya, Takuya, Ohi, Yasuyo, Osborne, C Kent, Penault-Llorca, Frédérique M, Piper, Tammy, Porter, Peggy L, Sakatani, Takashi, Salgado, Roberto, Starczynski, Jane, Lænkholm, Anne-Vibeke, Viale, Giuseppe, Dowsett, Mitch, Hayes, Daniel F, and Nielsen, Torsten O
- Published
- 2015
- Full Text
- View/download PDF
9. Discordance between Immunohistochemistry and ERBB2 mRNA to Determine HER2 Low Status for Breast Cancer
- Author
-
Xu, Keying, Bayani, Jane, Mallon, Elizabeth, Pond, Gregory R., Piper, Tammy, Hasenburg, Annette, Markopoulos, Christos J., Dirix, Luc, Seynaeve, Caroline M., Van De Velde, Cornelis J.h., Rea, Daniel W., and Bartlett, John M.S.
- Abstract
Novel HER2-directed antibody-drug conjugates (ADC) have demonstrated efficacy in HER2-low expressing breast cancers, which are currently defined as those with IHC scores of 1+ or 2+ with a negative ISH assay. However, current HER2 testing methods are designed to identify HER2 amplified tumors with “high” expression levels. The true definition of “HER2-low” expressing breast cancers remains controversial. Using quantitative molecular analysis of breast cancers based on RNA expression, the dynamic range of HER2 expression exceeds that detected by in situ IHC approaches. ERBB2 mRNA expression levels across IHC groups using patient samples derived from the Tamoxifen Exemestane Adjuvant Multicenter (TEAM) Trial were investigated. The standardized mean differences in ERBB2 mRNA scores in log base 2 are 0.47 (95% CI: 0.36,0.57), 0.58 (95% CI: 0.26,0.70), and 0.32 (95% CI: -0.12,0.75) when comparing IHC 0+ without staining vs IHC 0+ with some staining, IHC 0+ with some staining vs IHC 1+, and IHC 1+ vs IHC 2+/FISH-ve, respectively. The results showed that immunohistochemical methods have a comparatively limited dynamic range for measuring HER2 protein expression. The range of expression based on RNA abundance suggest that a molecular method defining HER2-low cancers may better serve the treatment decision needs of this group. Indeed, the validity of RNA abundance to identify HER2-low cancers and predict treatment response need to be further evaluated by prospective clinical trials.
- Published
- 2022
10. Comparative survival analysis of multiparametric tests-when molecular tests disagree-A TEAM Pathology study
- Author
-
Bartlett, John M. S. Bayani, Jane Kornaga, Elizabeth Xu, Keying Pond, Greg R. Piper, Tammy Mallon, Elizabeth Yao, Cindy Q. Boutros, Paul C. Hasenburg, Annette Dunn, J. A. and Markopoulos, Christos Dirix, Luc Seynaeve, Caroline van de Velde, Cornelis J. H. Stein, Robert C. Rea, Daniel
- Subjects
education - Abstract
Multiparametric assays for risk stratification are widely used in the management of both node negative and node positive hormone receptor positive invasive breast cancer. Recent data from multiple sources suggests that different tests may provide different risk estimates at the individual patient level. The TEAM pathology study consists of 3284 postmenopausal ER+ve breast cancers treated with endocrine therapy Using genes comprising the following multi-parametric tests OncotypeDx(R), Prosigna (TM) and MammaPrint(R) signatures were trained to recapitulate true assay results. Patients were then classified into risk groups and survival assessed. Whilst likelihood chi(2) ratios suggested limited value for combining tests, Kaplan-Meier and LogRank tests within risk groups suggested combinations of tests provided statistically significant stratification of potential clinical value. Paradoxically whilst Prosigna-trained results stratified Oncotype-trained subgroups across low and intermediate risk categories, only intermediate risk Prosigna-trained cases were further stratified by Oncotype-trained results. Both Oncotype-trained and Prosigna-trained results further stratified MammaPrint-trained low risk cases, and MammaPrint-trained results also stratified Oncotype-trained low and intermediate risk groups but not Prosigna-trained results. Comparisons between existing multiparametric tests are challenging, and evidence on discordance between tests in risk stratification presents further dilemmas. Detailed analysis of the TEAM pathology study suggests a complex inter-relationship between test results in the same patient cohorts which requires careful evaluation regarding test utility. Further prognostic improvement appears both desirable and achievable.
- Published
- 2021
11. Phosphorylation of AKT pathway proteins is not predictive of benefit of taxane therapy in early breast cancer
- Author
-
Bartlett, John M. S., A’Hern, Roger, Piper, Tammy, Ellis, Ian O., Dowsett, Mitch, Mallon, Elizabeth A., Cameron, David A., Johnston, Stephen, Bliss, Judith M., Ellis, Paul, and Barrett-Lee, Peter J.
- Published
- 2013
- Full Text
- View/download PDF
12. An International Ki67 Reproducibility Study
- Author
-
Polley, Mei-Yin C., Leung, Samuel C. Y., McShane, Lisa M., Gao, Dongxia, Hugh, Judith C., Mastropasqua, Mauro G., Viale, Giuseppe, Zabaglo, Lila A., Penault-Llorca, Frédérique, Bartlett, John M.S., Gown, Allen M., Symmans, W. Fraser, Piper, Tammy, Mehl, Erika, Enos, Rebecca A., Hayes, Daniel F., Dowsett, Mitch, and Nielsen, Torsten O.
- Published
- 2013
- Full Text
- View/download PDF
13. Validation of the IHC4 Breast Cancer Prognostic Algorithm Using Multiple Approaches on the Multinational TEAM Clinical Trial
- Author
-
Bartlett, John M.S., Christiansen, Jason, Gustavson, Mark, Rimm, David L., Piper, Tammy, van de Velde, Cornelis J.H., Hasenburg, Annette, Kieback, Dirk G., Putter, Hein, Markopoulos, Christos J., Dirix, Luc Y., Seynaeve, Caroline, and Rea, Daniel W.
- Subjects
Clinical trials -- Models -- Health aspects ,Algorithms -- Models -- Health aspects ,Recurrence (Disease) -- Models -- Health aspects ,Immunohistochemistry -- Models -- Health aspects ,Medical research -- Models -- Health aspects ,Tamoxifen -- Models -- Health aspects ,Exemestane -- Models -- Health aspects ,Breast cancer -- Models -- Health aspects ,Algorithm ,Health - Abstract
Context.--Hormone receptors HER2/neu and Ki-67 are markers of residual risk in early breast cancer. An algorithm (IHC4) combining these markers may provide additional information on residual risk of recurrence in patients treated with hormone therapy. Objective.--To independently validate the IHC4 algorithm in the multinational Tamoxifen Versus Exemestane Adjuvant Multicenter Trial (TEAM) cohort, originally developed on the trans-ATAC (Arimidex, Tamoxifen, Alone or in Combination Trial) cohort, by comparing 2 methodologies. Design.--The IHC4 biomarker expression was quantified on TEAM cohort samples (n = 2919) by using 2 independent methodologies (conventional 3,30-diaminobezidine [DAB] immunohistochemistry with image analysis and standardized quantitative immunofluorescence [QIF] by AQUA technology). The IHC4 scores were calculated by using the same previously established coefficients and then compared with recurrence-free and distant recurrence-free survival, using multivariate Cox proportional hazards modeling. Results.--The QIF model was highly significant for prediction of residual risk (P < .001), with continuous model scores showing a hazard ratio (HR) of 1.012 (95% confidence interval [95% CI]: 1.010-1.014), which was significantly higher than that for the DAB model (HR: 1.008, 95% CI: 1.006-1.009); P < .001). Each model added significant prognostic value in addition to recognized clinical prognostic factors, including nodal status, in multivariate analyses. Quantitative immunofluorescence, however, showed more accuracy with respect to overall residual risk assessment than the DAB model. Conclusions.--The use of the IHC4 algorithm was validated on the TEAM trial for predicting residual risk in patients with breast cancer. These data support the use of the IHC4 algorithm clinically, but quantitative and standardized approaches need to be used. (Arch Pathol Lab Med. 2016; 140:66-74; doi: 10.5858/arpa.2014-0599-OA), With progressively improving outcomes, particularly for patients with estrogen receptor (ER)-positive early breast cancers, personalized risk stratification to direct appropriate therapy is increasingly important. Multiple approaches to the assessment of [...]
- Published
- 2016
- Full Text
- View/download PDF
14. Nottingham Prognostic Index Plus: Validation of a clinical decision making tool in breast cancer in an independent series
- Author
-
Green, Andrew R., Soria, Daniele, Stephen, Jacquelin, Powe, Desmond G., Nolan, Christopher C., Kunkler, Ian, Thomas, Jeremy, Kerr, Gillian R., Jack, Wilma, Cameron, David, Piper, Tammy, Ball, Graham R., Garibaldi, Jonathan M., Rakha, Emad, Bartlett, John M.S., and Ellis, Ian O.
- Subjects
Nottingham Breast Cancer Research Centre ,breast cancer ,classification ,outcom ,mental disorders ,prognostic index ,outcome ,Original Article ,Original Articles ,molecular ,QA ,humanities ,clinical - Abstract
The Nottingham Prognostic Index Plus (NPI+) is a clinical decision making tool in breast cancer (BC) that aims to provide improved patient outcome stratification superior to the traditional NPI. This study aimed to validate the NPI+ in an independent series of BC. Eight hundred and eighty five primary early stage BC cases from Edinburgh were semi‐quantitatively assessed for 10 biomarkers [Estrogen Receptor (ER), Progesterone Receptor (PgR), cytokeratin (CK) 5/6, CK7/8, epidermal growth factor receptor (EGFR), HER2, HER3, HER4, p53, and Mucin 1] using immunohistochemistry and classified into biological classes by fuzzy logic‐derived algorithms previously developed in the Nottingham series. Subsequently, NPI+ Prognostic Groups (PGs) were assigned for each class using bespoke NPI‐like formulae, previously developed in each NPI+ biological class of the Nottingham series, utilising clinicopathological parameters: number of positive nodes, pathological tumour size, stage, tubule formation, nuclear pleomorphism and mitotic counts. Biological classes and PGs were compared between the Edinburgh and Nottingham series using Cramer's V and their role in patient outcome prediction using Kaplan–Meier curves and tested using Log Rank. The NPI+ biomarker panel classified the Edinburgh series into seven biological classes similar to the Nottingham series (p > 0.01). The biological classes were significantly associated with patient outcome (p 0.01). The good PGs were similarly validated in Luminal B, Basal p53 normal, HER2+/ER− tumours and the poor PG in the Luminal N class (p > 0.01). Due to small patient numbers assigned to the remaining PGs, Luminal N, Luminal B, Basal p53 normal and HER2+/ER− classes could not be validated. This study demonstrates the reproducibility of NPI+ and confirmed its prognostic value in an independent cohort of primary BC. Further validation in large randomised controlled trial material is warranted.
- Published
- 2016
15. The Challenges of Data Access for Historical Clinical Trials: A user experience
- Author
-
Piper, Tammy
- Subjects
Clinical Trials ,Research Data - Abstract
Many trials from yesteryear looked at the benefit of treatment A v treatment B in terms of recurrence and survival data only. With the advent of new research methods available such as whole genome sequencing, digital image analysis, Nanostring technologies, there is a burgeoning trend towards revisiting these older cohorts to collect tissue samples and update the follow-up data. The idea of applying modern research techniques to historic tissue cohorts with 30 years of follow-up data is attractive to commercial investors who are trying to validate new personalised medicine approaches to breast cancer treatments. Applying new methods to patient samples from long ago combined with a wealth of long term follow up is a dream research project. However it is not without several hurdles to overcome. Patient consent was gathered in a more lax way back in the early 1990’s so although patients consented to enter a trial, the process would not have been as rigorously documented as it is today. This means accessing these patients data records causes issue as we do not have ‘explicit informed consent’ to do so. We could go back to patients and re-consent them but this brings its own issues. How do we locate these patients to get permission to access their patient records without accessing the patient records to find out if they are still alive or are mentally competent to be re-consented? What data do you require from the patient records? The date of death and /or relapse? Or more specific data such as tumour grade, patient age at diagnosis, surgery or death? Where will the data be stored and who will have access to such data? This is the biggest hurdle we have faced as with overseas funders unable to perform their own analysis on their own sequencing data as the patient derived data must not leave the UK/EU. With the introduction of the Patient Benefit and Privacy Panel in 2016 and the introduction of the new GDPR regulations in May 2018 the access and use of data seems to be getting tighter yet the opportunities to use it keep expanding. Finding the correct balance to satisfy the regulators is key. A video of this presentation can be viewed at https://media.ed.ac.uk/media/0_z6dtx4zx
- Published
- 2017
16. Computational approaches to support comparative analysis of multiparametric tests: Modelling versus Training.
- Author
-
Bartlett, John M. S., Bayani, Jane, Kornaga, Elizabeth N., Danaher, Patrick, Crozier, Cheryl, Piper, Tammy, Yao, Cindy Q., Dunn, Janet A., Boutros, Paul C., and Stein, Robert C.
- Subjects
MEDICAL personnel ,COMPARATIVE studies ,BODY-weight-supported treadmill training - Abstract
Multiparametric assays for risk stratification are widely used in the management of breast cancer, with applications being developed for a number of other cancer settings. Recent data from multiple sources suggests that different tests may provide different risk estimates at the individual patient level. There is an increasing need for robust methods to support cost effective comparisons of test performance in multiple settings. The derivation of similar risk classifications using genes comprising the following multi-parametric tests Oncotype DX
® (Genomic Health.), Prosigna™ (NanoString Technologies, Inc.), MammaPrint® (Agendia Inc.) was performed using different computational approaches. Results were compared to the actual test results. Two widely used approaches were applied, firstly computational "modelling" of test results using published algorithms and secondly a "training" approach which used reference results from the commercially supplied tests. We demonstrate the potential for errors to arise when using a "modelling" approach without reference to real world test results. Simultaneously we show that a "training" approach can provide a highly cost-effective solution to the development of real-world comparisons between different multigene signatures. Comparisons between existing multiparametric tests is challenging, and evidence on discordance between tests in risk stratification presents further dilemmas. We present an approach, modelled in breast cancer, which can provide health care providers and researchers with the potential to perform robust and meaningful comparisons between multigene tests in a cost-effective manner. We demonstrate that whilst viable estimates of gene signatures can be derived from modelling approaches, in our study using a training approach allowed a close approximation to true signature results. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
17. Validation of the IHC4 Breast Cancer Prognostic Algorithm Using Multiple Approaches on the Multinational TEAM Clinical Trial
- Author
-
Bartlett, John M. S. Christiansen, Jason Gustavson, Mark and Rimm, David L. Piper, Tammy van de Velde, Cornelis J. H. and Hasenburg, Annette Kieback, Dirk G. Putter, Hein and Markopoulos, Christos J. Dirix, Luc Y. Seynaeve, Caroline and Rea, Daniel W.
- Abstract
Context.-Hormone receptors HER2/neu and Ki-67 are markers of residual risk in early breast cancer. An algorithm (IHC4) combining these markers may provide additional information on residual risk of recurrence in patients treated with hormone therapy. Objective.-To independently validate the IHC4 algorithm in the multinational Tamoxifen Versus Exemestane Adjuvant Multicenter Trial (TEAM) cohort, originally developed on the trans-ATAC (Arimidex, Tamoxifen, Alone or in Combination Trial) cohort, by comparing 2 methodologies. Design.-The IHC4 biomarker expression was quantified on TEAM cohort samples (n = 2919) by using 2 independent methodologies (conventional 3,3’-diaminobezidine [DAB] immunohistochemistry with image analysis and standardized quantitative immunofluorescence [QIF] by AQUA technology). The IHC4 scores were calculated by using the same previously established coefficients and then compared with recurrence-free and distant recurrence-free survival, using multivariate Cox proportional hazards modeling. Results.-The QIF model was highly significant for prediction of residual risk (P < .001), with continuous model scores showing a hazard ratio (HR) of 1.012 (95% confidence interval [95% CI]: 1.010-1.014), which was significantly higher than that for the DAB model (HR: 1.008, 95% CI: 1.006-1.009); P < .001). Each model added significant prognostic value in addition to recognized clinical prognostic factors, including nodal status, in multivariate analyses. Quantitative immunofluorescence, however, showed more accuracy with respect to overall residual risk assessment than the DAB model. Conclusions.-The use of the IHC4 algorithm was validated on the TEAM trial for predicting residual risk in patients with breast cancer. These data support the use of the IHC4 algorithm clinically, but quantitative and standardized approaches need to be used.
- Published
- 2016
18. Time dependence of biomarkers: Non-proportional effects of immunohistochemical panels predicting relapse risk in early breast cancer
- Author
-
Stephen, Jacqueline Murray, Gordon Cameron, David Thomas, Jeremy Kunkler, Ian Jack, Wilma Kerr, Gill Piper, Tammy and Brookes, Cassandra Rea, Daniel van de Velde, Cornelis and Hasenburg, Annette Markopoulos, Christos Dirix, Luc and Seynaeve, Caroline Bartlett, John
- Published
- 2015
19. Mutational Analysis of PI3K/AKT Signaling Pathway in Tamoxifen Exemestane Adjuvant Multinational Pathology Study
- Author
-
Sabine, Vicky S. Crozier, Cheryl Brookes, Cassandra L. and Drake, Camilla Piper, Tammy van de Velde, Cornelis J. H. and Hasenburg, Annette Kieback, Dirk G. Markopoulos, Christos and Dirix, Luc Seynaeve, Caroline Rea, Daniel W. Bartlett, John M. S.
- Subjects
neoplasms - Abstract
Purpose Deregulation of key PI3K/AKT pathway genes may contribute to endocrine resistance in breast cancer (BC). PIK3CA is the most frequently mutated gene in luminal BC (similar to 35%); however, the effect of mutations in helical versus kinase domains remains controversial. We hypothesize that improved outcomes occur in patients with estrogen receptor-positive (ER positive) BC receiving endocrine therapy and possessing PIK3CA mutations. Materials and Methods DNA was extracted from 4,540 formalin-fixed paraffin-embedded BC samples from the Exemestane Versus Tamoxifen-Exemestane pathology study. Mutational analyses were performed for 25 mutations (PIK3CAx10, AKT1x1, KRASx5, HRASx3, NRASx2 and BRAFx4). Results PIK3CA mutations were frequent (39.8%), whereas RAS/RAF mutations were rare (
- Published
- 2014
20. Mammostrat As an Immunohistochemical Multigene Assay for Prediction of Early Relapse Risk in the Tamoxifen Versus Exemestane Adjuvant Multicenter Trial Pathology Study
- Author
-
Bartlett, John M. S. Bloom, Kenneth J. Piper, Tammy Lawton, Thomas J. van de Velde, Cornelis J. H. Ross, Douglas T. and Ring, Brian Z. Seitz, Robert S. Beck, Rodney A. Hasenburg, Annette Kieback, Dirk Putter, Hein Markopoulos, Christos and Dirix, Luc Seynaeve, Caroline Rea, Daniel
- Abstract
Purpose Some postmenopausal patients with hormone-sensitive early breast cancer remain at high risk of relapse despite endocrine therapy and, in addition, might benefit from adjuvant chemotherapy. The challenge is to prospectively identify such patients. The Mammostrat test uses five immunohistochemical markers to stratify patients regarding recurrence risk and may inform treatment decisions. We tested the efficacy of this panel in the Tamoxifen versus Exemestane Adjuvant Multicenter (TEAM) trial. Patients and Methods Pathology blocks from 4,598 TEAM patients were collected, and tissue microarrays (TMAs) were constructed. The cohort was 47% node-positive, and 36% of patients in the cohort were treated with adjuvant chemotherapy. Triplicate 0.6-mm(2) TMA cores were stained, and positivity for p53, HTF9C, CEACAM5, NDRG1, and SLC7A5 was assessed. Cases were assigned a Mammostrat risk score, and distant relapse-free survival (DRFS) and disease-free survival (DFS) were analyzed. Results In multivariate regression analyses, which were corrected for conventional clinicopathologic markers, Mammostrat provided significant additional information on DRFS after endocrine therapy in estrogen receptor (ER) -positive node-negative patients (n = 1,226) who did not receive chemotherapy (P=.004). Additional analyses in all patients not exposed to chemotherapy, irrespective of nodal status (n = 2,559) and in the entire cohort (n = 3,837) showed Mammostrat scores provided additional information on DRFS in these groups (P=.001 and P
- Published
- 2012
21. Mutational analysis of PI3K/AKT signaling pathway in tamoxifen exemestane adjuvant multinational pathology study.
- Author
-
Sabine, Vicky S, Crozier, Cheryl, Brookes, Cassandra L, Drake, Camilla, Piper, Tammy, van de Velde, Cornelis J H, Hasenburg, Annette, Kieback, Dirk G, Markopoulos, Christos, Dirix, Luc, Seynaeve, Caroline, Rea, Daniel W, and Bartlett, John M S
- Published
- 2014
- Full Text
- View/download PDF
22. Mammostrat As an Immunohistochemical Multigene Assay for Prediction of Early Relapse Risk in the Tamoxifen Versus Exemestane Adjuvant Multicenter Trial Pathology Study.
- Author
-
Bartlett, John M. S., Bloom, Kenneth J., Piper, Tammy, Lawton, Thomas J., de Velde, Cornelis J. H. van, Ross, Douglas T., Ring, Brian Z., Seitz, Robert S., Beck, Rodney A., Hasenburg, Annette, Kieback, Dirk, Putter, Hein, Markopoulos, Christos, Dirix, Luc, Seynaeve, Caroline, and Rea, Daniel
- Published
- 2012
- Full Text
- View/download PDF
23. Analytical validation of a standardized scoring protocol for Ki67 assessed on breast excision whole sections: An international multicenter collaboration
- Author
-
Nielsen, Torsten O., Leung, Samuel C. Y., Zabaglo, Lila A., Arun, Indu, Badve, Sunil S., Bane, Anita L., Bartlet, John M. S., Borgquist, Signe, Chang, Martin C., Dodson, Andrew, Ehinger, Anna, Fineberg, Susan, Focke, Cornelia M., Gao, Dongxia, Gown, Allen M., Gutierrez, Carolina, Hugh, Judith C., Kos, Zuzana, Laenkholm, Anne-Vibeke, Mastropasqua, Mauro G., Moriya, Takuya, Nofech-Mozes, Sharon, Osborne, C. Kent, Penault-Llorca, Frederique M., Piper, Tammy, Sakatani, Takashi, Salgado, Roberto, Starczynski, Jane, Sugie, Tomoharu, van der Vegt, Bert, Viale, Giuseppe, Hayes, Daniel F., McShane, Lisa M., Dowsett, Mitch, and Damage and Repair in Cancer Development and Cancer Treatment (DARE)
24. Postoperative radiotherapy in women with early operable breast cancer (Scottish Breast Conservation Trial): 30-year update of a randomised, controlled, phase 3 trial.
- Author
-
Williams LJ, Kunkler IH, Taylor KJ, Dunlop J, Piper T, Caldwell J, Jack W, Loane JF, Elder K, Bartlett JMS, Dixon JM, and Cameron DA
- Abstract
Background: Breast-conserving surgery, adjuvant systemic therapy, and radiotherapy are the standard of care for most women with early breast cancer. There are few reports of clinical outcomes beyond the first decade of follow-up of randomised trials comparing breast-conserving surgery with or without radiotherapy. We present a 30-year update of the Scottish Breast Conservation Trial., Methods: In this randomised, controlled, phase 3 trial across 14 hospitals in Scotland, women aged younger than 70 years with early breast cancer (tumours ≤4 cm [T1 or T2 and N0 or N1]) were included. They underwent breast-conserving surgery (1 cm margin) with axillary node sampling or clearance. Oestrogen receptor (ER)-rich patients (≥20 fmol/mg protein) received 20 mg oral tamoxifen daily for 5 years. ER-poor patients (<20 fmol/mg protein) received chemotherapy (cyclophosphamide 600 mg/m
2 , methotrexate 50 mg/m2 , and fluorouracil 600 mg/m2 every 21 days intravenously in eight courses). Stratification was by menstrual status (within or more than 12 months from last menstrual period) and ER status (oestrogen concentration ≥20 fmol/mg protein, <20 fmol/mg protein, or unknown) and patients were randomly assigned (1:1) to high-dose (50 Gy in 20-25 fractions) local or locoregional radiotherapy versus no radiotherapy. No blinding was possible due to the nature of the treatment. We report the primary endpoint of the original trial, ipsilateral breast tumour recurrence, and the co-primary endpoint, overall survival. Clinical outcomes were compared by the log-rank test. Hazard ratios (HRs) are reported, with no radiotherapy as the reference group. Failures of the proportional hazards assumption are reported if significant. All analyses are by intention to treat., Findings: Between April 1, 1985, and Oct 2, 1991, 589 patients were enrolled and randomly assigned to the two treatment groups (293 to radiotherapy and 296 to no radiotherapy). After exclusion of four ineligible patients (two in each group), there were 291 patients in the radiotherapy group and 294 patients in the no radiotherapy group. Median follow-up was 17·5 years (IQR 8·4-27·9). Ipsilateral breast tumour recurrence was significantly lower in the radiotherapy group than in the no radiotherapy group (46 [16%] of 291 vs 107 [36%] of 294; HR 0·39 [95% CI 0·28-0·55], p<0·0001). Although there were differences in the hazard rate for ipsilateral breast tumour recurrence in the first decade after treatment (HR 0·24 [95% CI 0·15-0·38], p<0·0001), subsequent risks of ipsilateral breast tumour recurrence were similar in both groups (0·98 [0·54-1·79], p=0·95). There was no difference in overall survival between the two groups (median 18·7 years [95% CI 16·5-21·5] in the no radiotherapy group vs 19·2 years [16·9-21·3] in the radiotherapy group; HR 1·08 [95% CI 0·89-1 ·30], log-rank p=0·43)., Interpretation: Our findings suggest that patients whose biology predicts a late relapse a decade or more after breast-conserving surgery for early breast cancer might gain little from adjuvant radiotherapy., Funding: Breast Cancer Institute (part of Edinburgh and Lothian Health Foundation) and PFS Genomics (now part of Exact Sciences)., Competing Interests: Declaration of interests We declare no competing interests., (© 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)- Published
- 2024
- Full Text
- View/download PDF
25. Discordance between Immunohistochemistry and Erb-B2 Receptor Tyrosine Kinase 2 mRNA to Determine Human Epidermal Growth Factor Receptor 2 Low Status for Breast Cancer.
- Author
-
Xu K, Bayani J, Mallon E, Pond GR, Piper T, Hasenburg A, Markopoulos CJ, Dirix L, Seynaeve CM, van de Velde CJH, Rea DW, and Bartlett JMS
- Subjects
- Biomarkers, Tumor metabolism, Female, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence methods, Prospective Studies, RNA, Messenger genetics, RNA, Messenger metabolism, Breast Neoplasms pathology, Receptor, ErbB-2 genetics, Receptor, ErbB-2 metabolism
- Abstract
Novel human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugates have demonstrated efficacy in HER2-low expressing breast cancers, which are currently defined as those with immunohistochemistry (IHC) scores of 1+ or 2+ with a negative in situ hybridization assay. However, current HER2 testing methods are designed to identify HER2-amplified tumors with high expression levels. The true definition of HER2-low expressing breast cancers remains controversial. Using quantitative molecular analysis of breast cancers based on RNA expression, the dynamic range of HER2 expression exceeds that detected by in situ IHC approaches. Erb-B2 receptor tyrosine kinase 2 (ERBB2) mRNA expression levels across IHC groups using patient samples derived from the Tamoxifen Exemestane Adjuvant Multicenter Trial were investigated. The standardized mean differences in ERBB2 mRNA scores in log base 2 are 0.47 (95% CI, 0.36-0.57), 0.58 (95% CI, 0.26-0.70), and 0.32 (95% CI, -0.12 to 0.75) when comparing IHC 0+ without staining versus IHC 0+ with some staining, IHC 0+ with some staining versus IHC 1+, and IHC 1+ versus IHC 2+/fluorescence in situ hybridization-negative, respectively. The results showed immunohistochemical methods have a comparatively limited dynamic range for measuring HER2 protein expression. The range of expression based on RNA abundance suggests a molecular method defining HER2-low cancers may better serve the treatment decision needs of this group. Indeed, the validity of RNA abundance to identify HER2-low cancers and predict treatment response needs to be further evaluated by prospective clinical trials., (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
26. Breast Cancer Index Is a Predictive Biomarker of Treatment Benefit and Outcome from Extended Tamoxifen Therapy: Final Analysis of the Trans-aTTom Study.
- Author
-
Bartlett JMS, Sgroi DC, Treuner K, Zhang Y, Piper T, Salunga RC, Ahmed I, Doos L, Thornber S, Taylor KJ, Brachtel EF, Pirrie SJ, Schnabel CA, and Rea DW
- Subjects
- Antineoplastic Agents, Hormonal therapeutic use, Biomarkers, Chemotherapy, Adjuvant methods, Disease-Free Survival, Female, Humans, Neoplasm Recurrence, Local drug therapy, Prognosis, Tamoxifen therapeutic use, Treatment Outcome, Breast Neoplasms diagnosis, Breast Neoplasms drug therapy
- Abstract
Purpose: The Breast Cancer Index (BCI) HOXB13/IL17BR (H/I) ratio predicts benefit from extended endocrine therapy in hormone receptor-positive (HR+) early-stage breast cancer. Here, we report the final analysis of the Trans-aTTom study examining BCI (H/I)'s predictive performance., Experimental Design: BCI results were available for 2,445 aTTom trial patients. The primary endpoint of recurrence-free interval (RFI) and secondary endpoints of disease-free interval (DFI) and disease-free survival (DFS) were examined using Cox proportional hazards regression and log-rank test., Results: Final analysis of the overall study population (N = 2,445) did not show a significant improvement in RFI with extended tamoxifen [HR, 0.90; 95% confidence interval (CI), 0.69-1.16; P = 0.401]. Both the overall study population and N0 group were underpowered due to the low event rate in the N0 group. In a pre-planned analysis of the N+ subset (N = 789), BCI (H/I)-High patients derived significant benefit from extended tamoxifen (9.7% absolute benefit: HR, 0.33; 95% CI, 0.14-0.75; P = 0.016), whereas BCI (H/I)-Low patients did not (-1.2% absolute benefit; HR, 1.11; 95% CI, 0.76-1.64; P = 0.581). A significant treatment-to-biomarker interaction was demonstrated on the basis of RFI, DFI, and DFS (P = 0.037, 0.040, and 0.025, respectively). BCI (H/I)-High patients remained predictive of benefit from extended tamoxifen in the N+/HER2- subgroup (9.4% absolute benefit: HR, 0.35; 95% CI, 0.15-0.81; P = 0.047). A three-way interaction evaluating BCI (H/I), treatment, and HER2 status was not statistically significant (P = 0.849)., Conclusions: Novel findings demonstrate that BCI (H/I) significantly predicts benefit from extended tamoxifen in HR+ N+ patients with HER2- disease. Moreover, BCI (H/I) demonstrates significant treatment to biomarker interaction across survival outcomes., (©2022 The Authors; Published by the American Association for Cancer Research.)
- Published
- 2022
- Full Text
- View/download PDF
27. Analytical validation of a standardised scoring protocol for Ki67 immunohistochemistry on breast cancer excision whole sections: an international multicentre collaboration.
- Author
-
Leung SCY, Nielsen TO, Zabaglo LA, Arun I, Badve SS, Bane AL, Bartlett JMS, Borgquist S, Chang MC, Dodson A, Ehinger A, Fineberg S, Focke CM, Gao D, Gown AM, Gutierrez C, Hugh JC, Kos Z, Laenkholm AV, Mastropasqua MG, Moriya T, Nofech-Mozes S, Osborne CK, Penault-Llorca FM, Piper T, Sakatani T, Salgado R, Starczynski J, Sugie T, van der Vegt B, Viale G, Hayes DF, McShane LM, and Dowsett M
- Subjects
- Female, Humans, Observer Variation, Reproducibility of Results, Biomarkers, Tumor analysis, Breast Neoplasms, Immunohistochemistry standards, Ki-67 Antigen analysis, Pathology, Clinical standards
- Abstract
Aims: The nuclear proliferation marker Ki67 assayed by immunohistochemistry has multiple potential uses in breast cancer, but an unacceptable level of interlaboratory variability has hampered its clinical utility. The International Ki67 in Breast Cancer Working Group has undertaken a systematic programme to determine whether Ki67 measurement can be analytically validated and standardised among laboratories. This study addresses whether acceptable scoring reproducibility can be achieved on excision whole sections., Methods and Results: Adjacent sections from 30 primary ER
+ breast cancers were centrally stained for Ki67 and sections were circulated among 23 pathologists in 12 countries. All pathologists scored Ki67 by two methods: (i) global: four fields of 100 tumour cells each were selected to reflect observed heterogeneity in nuclear staining; (ii) hot-spot: the field with highest apparent Ki67 index was selected and up to 500 cells scored. The intraclass correlation coefficient (ICC) for the global method [confidence interval (CI) = 0.87; 95% CI = 0.799-0.93] marginally met the prespecified success criterion (lower 95% CI ≥ 0.8), while the ICC for the hot-spot method (0.83; 95% CI = 0.74-0.90) did not. Visually, interobserver concordance in location of selected hot-spots varies between cases. The median times for scoring were 9 and 6 min for global and hot-spot methods, respectively., Conclusions: The global scoring method demonstrates adequate reproducibility to warrant next steps towards evaluation for technical and clinical validity in appropriate cohorts of cases. The time taken for scoring by either method is practical using counting software we are making publicly available. Establishment of external quality assessment schemes is likely to improve the reproducibility between laboratories further., (© 2019 John Wiley & Sons Ltd.)- Published
- 2019
- Full Text
- View/download PDF
28. Analytical validation of a standardized scoring protocol for Ki67: phase 3 of an international multicenter collaboration.
- Author
-
Leung SCY, Nielsen TO, Zabaglo L, Arun I, Badve SS, Bane AL, Bartlett JMS, Borgquist S, Chang MC, Dodson A, Enos RA, Fineberg S, Focke CM, Gao D, Gown AM, Grabau D, Gutierrez C, Hugh JC, Kos Z, Lænkholm AV, Lin MG, Mastropasqua MG, Moriya T, Nofech-Mozes S, Osborne CK, Penault-Llorca FM, Piper T, Sakatani T, Salgado R, Starczynski J, Viale G, Hayes DF, McShane LM, and Dowsett M
- Abstract
Pathological analysis of the nuclear proliferation biomarker Ki67 has multiple potential roles in breast and other cancers. However, clinical utility of the immunohistochemical (IHC) assay for Ki67 immunohistochemistry has been hampered by unacceptable between-laboratory analytical variability. The International Ki67 Working Group has conducted a series of studies aiming to decrease this variability and improve the evaluation of Ki67. This study tries to assess whether acceptable performance can be achieved on prestained core-cut biopsies using a standardized scoring method. Sections from 30 primary ER+ breast cancer core biopsies were centrally stained for Ki67 and circulated among 22 laboratories in 11 countries. Each laboratory scored Ki67 using three methods: (1) global (4 fields of 100 cells each); (2) weighted global (same as global but weighted by estimated percentages of total area); and (3) hot-spot (single field of 500 cells). The intraclass correlation coefficient (ICC), a measure of interlaboratory agreement, for the unweighted global method (0.87; 95% credible interval (CI): 0.81-0.93) met the prespecified success criterion for scoring reproducibility, whereas that for the weighted global (0.87; 95% CI: 0.7999-0.93) and hot-spot methods (0.84; 95% CI: 0.77-0.92) marginally failed to do so. The unweighted global assessment of Ki67 IHC analysis on core biopsies met the prespecified criterion of success for scoring reproducibility. A few cases still showed large scoring discrepancies. Establishment of external quality assessment schemes is likely to improve the agreement between laboratories further. Additional evaluations are needed to assess staining variability and clinical validity in appropriate cohorts of samples., Competing Interests: J.M.S.B. has consulted for Insight Genetics and BioNTech and received compensation. T.O.N. has consulted for Nanostring and received compensation. C.K.O. has consulted for Astra Zeneca, Genentech and NanoString and received compensation. The remaining authors declare no conflict of interest.
- Published
- 2016
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.