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4. Functional RECAP (REpair CAPacity) assay identifies homologous recombination deficiency undetected by DNA-based BRCAness tests

Author

Meijer, Titia G., Nguyen, Luan, Van Hoeck, Arne, Sieuwerts, Anieta M., Verkaik, Nicole S., Ladan, Marjolijn M., Ruigrok-Ritstier, Kirsten, van Deurzen, Carolien H. M., van de Werken, Harmen J. G., Lips, Esther H., Linn, Sabine C., Memari, Yasin, Davies, Helen, Nik-Zainal, Serena, Kanaar, Roland, Martens, John W. M., Cuppen, Edwin, Jager, Agnes, and van Gent, Dik C.

Published
2022
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6. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author

Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Børresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Collée, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dörk, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., García-Sáenz, José A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., González-Neira, Anna, Alnæs, Grethe I. Grenaker, Grip, Mervi, Guénel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Krüger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, Håkan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa V., Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkäs, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Rüdiger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Schöttker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., García-Closas, Montserrat, and Chatterjee, Nilanjan

Published
2022
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8. Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study

Author

Van Bockstal, Mieke R., François, Aline, Altinay, Serdar, Arnould, Laurent, Balkenhol, Maschenka, Broeckx, Glenn, Burguès, Octavio, Colpaert, Cecile, Dedeurwaerdere, Franceska, Dessauvagie, Benjamin, Duwel, Valérie, Floris, Giuseppe, Fox, Stephen, Gerosa, Clara, Hastir, Delfyne, Jaffer, Shabnam, Kurpershoek, Eline, Lacroix-Triki, Magali, Laka, Andoni, Lambein, Kathleen, MacGrogan, Gaëtan Marie, Marchiò, Caterina, Martin Martinez, Maria-Dolores, Nofech-Mozes, Sharon, Peeters, Dieter, Ravarino, Alberto, Reisenbichler, Emily, Resetkova, Erika, Sanati, Souzan, Schelfhout, Anne-Marie, Schelfhout, Vera, Shaaban, Abeer, Sinke, Renata, Stanciu-Pop, Claudia M., van Deurzen, Carolien H. M., Van de Vijver, Koen K., Van Rompuy, Anne-Sophie, Vincent-Salomon, Anne, Wen, Hannah Y., Wong, Serena, Bouzin, Caroline, and Galant, Christine

Published
2021
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10. Expression and Localization of Ferritin-Heavy Chain Predicts Recurrence for Breast Cancer Patients with a BRCA1/2 Mutation

Author

Qu, Shuoying, primary, Timmermans, A. Mieke, additional, Heemskerk-Gerritsen, Bernadette A. M., additional, Trapman-Jansen, Anita M. A. C., additional, Broeren-Foekens, Renée, additional, Prager-van der Smissen, Wendy J. C., additional, El Hassnaoui, Hoesna, additional, van Tienhoven, Tim, additional, Bes-Stobbe, Claudia K., additional, Westenend, Pieter J., additional, van Deurzen, Carolien H. M., additional, Martens, John W. M., additional, Hooning, Maartje J., additional, and Hollestelle, Antoinette, additional

Published
2023
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13. Prediction of contralateral breast cancer: external validation of risk calculators in 20 international cohorts

Author

Giardiello, Daniele, Hauptmann, Michael, Steyerberg, Ewout W., Adank, Muriel A., Akdeniz, Delal, Blom, Jannet C., Blomqvist, Carl, Bojesen, Stig E., Bolla, Manjeet K., Brinkhuis, Mariël, Chang-Claude, Jenny, Czene, Kamila, Devilee, Peter, Dunning, Alison M., Easton, Douglas F., Eccles, Diana M., Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, García-Closas, Montserrat, Haeberle, Lothar, Haiman, Christopher A., Hall, Per, Hamann, Ute, Hopper, John L., Jager, Agnes, Jakubowska, Anna, Jung, Audrey, Keeman, Renske, Koppert, Linetta B., Kramer, Iris, Lambrechts, Diether, Le Marchand, Loic, Lindblom, Annika, Lubiński, Jan, Manoochehri, Mehdi, Mariani, Luigi, Nevanlinna, Heli, Oldenburg, Hester S. A., Pelders, Saskia, Pharoah, Paul D. P., Shah, Mitul, Siesling, Sabine, Smit, Vincent T. H. B. M., Southey, Melissa C., Tapper, William J., Tollenaar, Rob A. E. M., van den Broek, Alexandra J., van Deurzen, Carolien H. M., van Leeuwen, Flora E., van Ongeval, Chantal, Van’t Veer, Laura J., Wang, Qin, Wendt, Camilla, Westenend, Pieter J., Hooning, Maartje J., and Schmidt, Marjanka K.

Published
2020
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14. Interobserver variability in upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast: the DCISion study

Author

Dano, Hélène, Altinay, Serdar, Arnould, Laurent, Bletard, Noella, Colpaert, Cecile, Dedeurwaerdere, Franceska, Dessauvagie, Benjamin, Duwel, Valérie, Floris, Giuseppe, Fox, Stephen, Gerosa, Clara, Jaffer, Shabnam, Kurpershoek, Eline, Lacroix-Triki, Magali, Laka, Andoni, Lambein, Kathleen, MacGrogan, Gaëtan Marie, Marchió, Caterina, Martinez, Dolores Martin, Nofech-Mozes, Sharon, Peeters, Dieter, Ravarino, Alberto, Reisenbichler, Emily, Resetkova, Erika, Sanati, Souzan, Schelfhout, Anne-Marie, Schelfhout, Vera, Shaaban, Abeer M., Sinke, Renata, Stanciu-Pop, Claudia Maria, Stobbe, Claudia, van Deurzen, Carolien H. M., Van de Vijver, Koen, Van Rompuy, Anne-Sophie, Verschuere, Stephanie, Vincent-Salomon, Anne, Wen, Hannah, Bouzin, Caroline, Galant, Christine, and Van Bockstal, Mieke R.

Published
2020
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16. Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer.

Author

Leon-Ferre, Roberto A., Jonas, Sarah Flora, Salgado, Roberto, Loi, Sherene, de Jong, Vincent, Carter, Jodi M., Nielsen, Torsten O., Leung, Samuel, Riaz, Nazia, Chia, Stephen, Jules-Clément, Gérôme, Curigliano, Giuseppe, Criscitiello, Carmen, Cockenpot, Vincent, Lambertini, Matteo, Suman, Vera J., Linderholm, Barbro, Martens, John W. M., van Deurzen, Carolien H. M., and Timmermans, A. Mieke

Subjects
TRIPLE-negative breast cancer, TUMOR-infiltrating immune cells, CANCER relapse, RADIOTHERAPY, NEOADJUVANT chemotherapy, LIKELIHOOD ratio tests, PROGNOSIS
Abstract

Key Points: Question: In patients with early-stage triple-negative breast cancer (TNBC) treated with locoregional therapy but without adjuvant or neoadjuvant chemotherapy, is a higher abundance of tumor-infiltrating lymphocytes (TIL) in breast cancer tissue associated with better survival? Findings: In this retrospective analysis of 1966 participants with early-stage TNBC treated with locoregional therapy but without adjuvant or neoadjuvant chemotherapy, survival rates were 90% for patients with a TIL level of 50% or greater, compared with 72% for patients with a TIL level of less than 30% at 5-year follow-up. Meaning: In patients with early-stage TNBC treated with locoregional therapy only, higher TIL levels in breast cancer tissue were associated with improved survival. Importance: The association of tumor-infiltrating lymphocyte (TIL) abundance in breast cancer tissue with cancer recurrence and death in patients with early-stage triple-negative breast cancer (TNBC) who are not treated with adjuvant or neoadjuvant chemotherapy is unclear. Objective: To study the association of TIL abundance in breast cancer tissue with survival among patients with early-stage TNBC who were treated with locoregional therapy but no chemotherapy. Design, Setting, and Participants: Retrospective pooled analysis of individual patient-level data from 13 participating centers in North America (Rochester, Minnesota; Vancouver, British Columbia, Canada), Europe (Paris, Lyon, and Villejuif, France; Amsterdam and Rotterdam, the Netherlands; Milan, Padova, and Genova, Italy; Gothenburg, Sweden), and Asia (Tokyo, Japan; Seoul, Korea), including 1966 participants diagnosed with TNBC between 1979 and 2017 (with follow-up until September 27, 2021) who received treatment with surgery with or without radiotherapy but no adjuvant or neoadjuvant chemotherapy. Exposure: TIL abundance in breast tissue from resected primary tumors. Main Outcomes and Measures: The primary outcome was invasive disease-free survival [iDFS]. Secondary outcomes were recurrence-free survival [RFS], survival free of distant recurrence [distant RFS, DRFS], and overall survival. Associations were assessed using a multivariable Cox model stratified by participating center. Results: This study included 1966 patients with TNBC (median age, 56 years [IQR, 39-71]; 55% had stage I TNBC). The median TIL level was 15% (IQR, 5%-40%). Four-hundred seventeen (21%) had a TIL level of 50% or more (median age, 41 years [IQR, 36-63]), and 1300 (66%) had a TIL level of less than 30% (median age, 59 years [IQR, 41-72]). Five-year DRFS for stage I TNBC was 94% (95% CI, 91%-96%) for patients with a TIL level of 50% or more, compared with 78% (95% CI, 75%-80%) for those with a TIL level of less than 30%; 5-year overall survival was 95% (95% CI, 92%-97%) for patients with a TIL level of 50% or more, compared with 82% (95% CI, 79%-84%) for those with a TIL level of less than 30%. At a median follow-up of 18 years, and after adjusting for age, tumor size, nodal status, histological grade, and receipt of radiotherapy, each 10% higher TIL increment was associated independently with improved iDFS (hazard ratio [HR], 0.92 [0.89-0.94]), RFS (HR, 0.90 [0.87-0.92]), DRFS (HR, 0.87 [0.84-0.90]), and overall survival (0.88 [0.85-0.91]) (likelihood ratio test, P < 10e-6). Conclusions and Relevance: In patients with early-stage TNBC who did not undergo adjuvant or neoadjuvant chemotherapy, breast cancer tissue with a higher abundance of TIL levels was associated with significantly better survival. These results suggest that breast tissue TIL abundance is a prognostic factor for patients with early-stage TNBC. This study of patients with early-stage triple-negative breast cancer not treated with adjuvant or neoadjuvant chemotherapy analyzes the association between tumor-infiltrating lymphocyte levels, cancer recurrence, and survival. [ABSTRACT FROM AUTHOR]

Published
2024
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17. The effect of (neo)adjuvant chemotherapy on long‐term survival outcomes in patients with invasive lobular breast cancer treated with endocrine therapy: A retrospective cohort study.

Author

Öztekin, Selin, Hooning, Maartje J., van Deurzen, Carolien H. M., Dietvorst, Anne‐Marie H. P., Drooger, Jan C., Kitzen, Jos J. E. M., Martens, John W. M., van der Padt‐Pruijsten, Annemieke, Vastbinder, Mijntje B., Zuetenhorst, Hanneke, Heemskerk‐Gerritsen, Bernadette A. M., and Jager, Agnes

Subjects
LOBULAR carcinoma, HORMONE receptor positive breast cancer, ADJUVANT chemotherapy, HORMONE therapy, EPIDERMAL growth factor receptors, SURVIVAL rate, OVERALL survival
Abstract

Background: Despite histological and molecular differences between invasive lobular carcinoma (ILC) and invasive carcinoma of no special type, according to national treatment guidelines no distinction is made regarding the use of (neo)adjuvant chemotherapy. Studies on the long‐term outcome of chemotherapy in patients with ILC are scarce and show inconclusive results. Methods: All patients with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative ILC with an indication for chemotherapy treated with adjuvant endocrine therapy were selected from the Erasmus Medical Center Breast Cancer database. Cox proportional hazards models were used to estimate the effect of chemotherapy on recurrence‐free survival (RFS), breast cancer–specific survival (BCSS), and overall survival (OS). Results: A total of 520 patients were selected, of whom 379 were treated with chemotherapy and 141 were not. Patients in the chemotherapy group were younger (51 vs. 61 years old; p <.001), had a higher T status (T3+, 33% vs. 14%; p <.001), and more often had lymph node involvement (80% vs. 49%; p <.001) in comparison to the no‐chemotherapy group. After adjusting for confounders, chemotherapy treatment was not associated with better RFS (hazard ratio [HR], 1.20; 95% confidence interval [CI], 0.63–2.31), BCSS (HR, 1.24; 95% CI, 0.60–2.58), or OS (HR, 0.97; 95% CI, 0.56–1.66). This was also reflected by adjusted Cox survival curves in the chemotherapy versus no‐chemotherapy group for RFS (75% vs. 79%), BCSS (80% vs. 84%), and OS (72% vs. 71%). Conclusions: Chemotherapy is not associated with improved RFS, BCSS, or OS for patients with ER+/HER2− ILC treated with adjuvant endocrine therapy and with an indication for chemotherapy. Chemotherapy is not associated with improved recurrence‐free survival, breast cancer–specific survival, or overall survival for patients with estrogen receptor–positive/human epidermal growth factor receptor 2–negative invasive lobular carcinoma treated with endocrine therapy and with an indication for chemotherapy. [ABSTRACT FROM AUTHOR]

Published
2024
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18. The effect of (neo)adjuvant chemotherapy on long‐term survival outcomes in patients with invasive lobular breast cancer treated with endocrine therapy: A retrospective cohort study

Author

Öztekin, Selin, primary, Hooning, Maartje J., additional, van Deurzen, Carolien H. M., additional, Dietvorst, Anne‐Marie H. P., additional, Drooger, Jan C., additional, Kitzen, Jos J. E. M., additional, Martens, John W. M., additional, van der Padt‐Pruijsten, Annemieke, additional, Vastbinder, Mijntje B., additional, Zuetenhorst, Hanneke, additional, Heemskerk‐Gerritsen, Bernadette A. M., additional, and Jager, Agnes, additional

Published
2023
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24. Prediction and clinical utility of a contralateral breast cancer risk model

Author

Giardiello, Daniele, Steyerberg, Ewout W., Hauptmann, Michael, Adank, Muriel A., Akdeniz, Delal, Blomqvist, Carl, Bojesen, Stig E., Bolla, Manjeet K., Brinkhuis, Mariël, Chang-Claude, Jenny, Czene, Kamila, Devilee, Peter, Dunning, Alison M., Easton, Douglas F., Eccles, Diana M., Fasching, Peter A., Figueroa, Jonine, Flyger, Henrik, García-Closas, Montserrat, Haeberle, Lothar, Haiman, Christopher A., Hall, Per, Hamann, Ute, Hopper, John L., Jager, Agnes, Jakubowska, Anna, Jung, Audrey, Keeman, Renske, Kramer, Iris, Lambrechts, Diether, Le Marchand, Loic, Lindblom, Annika, Lubiński, Jan, Manoochehri, Mehdi, Mariani, Luigi, Nevanlinna, Heli, Oldenburg, Hester S. A., Pelders, Saskia, Pharoah, Paul D. P., Shah, Mitul, Siesling, Sabine, Smit, Vincent T. H. B. M., Southey, Melissa C., Tapper, William J., Tollenaar, Rob A. E. M., van den Broek, Alexandra J., van Deurzen, Carolien H. M., van Leeuwen, Flora E., van Ongeval, Chantal, Van’t Veer, Laura J., Wang, Qin, Wendt, Camilla, Westenend, Pieter J., Hooning, Maartje J., and Schmidt, Marjanka K.

Published
2019
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25. Expression and Localization of Ferritin-Heavy Chain Predicts Recurrence for Breast Cancer Patients with a BRCA1/2 Mutation.

Author

Qu, Shuoying, Timmermans, A. Mieke, Heemskerk-Gerritsen, Bernadette A. M., Trapman-Jansen, Anita M. A. C., Broeren-Foekens, Renée, Prager-van der Smissen, Wendy J. C., El Hassnaoui, Hoesna, van Tienhoven, Tim, Bes-Stobbe, Claudia K., Westenend, Pieter J., van Deurzen, Carolien H. M., Martens, John W. M., Hooning, Maartje J., and Hollestelle, Antoinette

Subjects
BREAST cancer prognosis, TISSUE arrays, GENETIC mutation, FERRITIN, IMMUNOHISTOCHEMISTRY, MULTIVARIATE analysis, CANCER relapse, GENE expression, OXIDATIVE stress, SURVIVAL analysis (Biometry), RESEARCH funding, TUMOR markers, DNA damage, PROGRESSION-free survival, T cells, BREAST tumors, ALGORITHMS
Abstract

Simple Summary: Ferritin is a ferroxidase, which protects cellular components from the potentially toxic effects of free iron. The expression and localization of ferritin-heavy chain (FTH1), the catalytic subunit of ferritin, was shown to predict survival for triple-negative breast cancer (BC) patients and be related to T-cell response. Here, we studied the association between FTH1 and time to survival in primary BCs from 222 BRCA1/2 mutation carriers. We found that nuclear, but not cytoplasmic, localization of FTH1 expression was associated with a shorter time to recurrence. In a subset of 51 BRCA1/2 mutation carriers, we evaluated the relation between localization and expression of FTH1 and T-cell response. However, we did not detect any association between FTH1 and the amount or composition of CD8+ cytotoxic, CD4+ helper, or FOXP3+ regulatory T cells. Further research is necessary to unravel the mechanism by which nuclear FTH1 influences the clinical outcome of BRCA1/2-associated BC patients. The ferritin-heavy chain (FTH1) is the catalytic subunit of the ferroxidase ferritin, which prevents oxidative DNA damage via intracellular iron storage. FTH1 was shown to be a prognostic marker for triple-negative breast cancer (BC) patients and associated with an enrichment of CD8+ effector T cells. However, whether the expression and localization of FTH1 are also associated with clinical outcome in other BC subtypes is unknown. Here, we investigated the association of FTH1 with time to survival in BCs from 222 BRCA1/2 mutation carriers by immunohistochemistry on tissue microarrays. In addition, for 51 of these patients, the association between FTH1 and specific subsets of T cells was evaluated on whole slides using automatic scoring algorithms. We revealed that nuclear FTH1 (nFTH1) expression, in multivariable analyses, was associated with a shorter disease-free (HR = 2.71, 95% CI = 1.49–4.92, p = 0.001) and metastasis-free survival (HR = 3.54, 95% CI = 1.45–8.66, p = 0.006) in patients carrying a BRCA1/2 mutation. However, we found no relation between cytoplasmic FTH1 expression and survival of BRCA1/2 mutation carriers. Moreover, we did not detect an association between FTH1 expression and the amount of CD45+ (p = 0.13), CD8+ (p = 0.18), CD4+ (p = 0.20) or FOXP3+ cells (p = 0.17). Consequently, the mechanism underlying the worse recurrence-free survival of nFTH1 expression in BRCA1/2 mutation carriers needs further investigation. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Risk of metachronous contralateral breast cancer in patients with primary invasive lobular breast cancer:Results from a nationwide cohort

Author

Akdeniz, Delal, Kramer, Iris, van Deurzen, Carolien H. M., Heemskerk-Gerritsen, Bernadette A. M., Schaapveld, Michael, Westenend, Pieter J., Voogd, Adri C., Jager, Agnes, Steyerberg, Ewout W., Sleijfer, Stefan, Schmidt, Marjanka K., Hooning, Maartje J., Akdeniz, Delal, Kramer, Iris, van Deurzen, Carolien H. M., Heemskerk-Gerritsen, Bernadette A. M., Schaapveld, Michael, Westenend, Pieter J., Voogd, Adri C., Jager, Agnes, Steyerberg, Ewout W., Sleijfer, Stefan, Schmidt, Marjanka K., and Hooning, Maartje J.

Abstract

Lobular primary breast cancer (PBC) histology has been proposed as a risk factor for contralateral breast cancer (CBC), but results have been inconsistent. We investigated CBC risk and the impact of systemic therapy in lobular versus ductal PBC. Further, CBC characteristics following these histologic subtypes were explored. We selected 74,373 women diagnosed between 2003 and 2010 with stage I-III invasive PBC from the nationwide Netherlands Cancer Registry. We assessed absolute risk of CBC taking into account competing risks among those with lobular (n = 8903), lobular mixed with other types (n = 3512), versus ductal (n = 62,230) histology. Hazard ratios (HR) for CBC were estimated in a cause-specific Cox model, adjusting for age at PBC diagnosis, radiotherapy, chemotherapy and/or endocrine therapy. Multivariable HRs for CBC were 1.18 (95% CI: 1.04-1.33) for lobular and 1.37 (95% CI: 1.16-1.63) for lobular mixed versus ductal PBC. Ten-year cumulative CBC incidences in patients with lobular, lobular mixed versus ductal PBC were 3.2%, 3.6% versus 2.8% when treated with systemic therapy and 6.6%, 7.7% versus 5.6% in patients without systemic therapy, respectively. Metachronous CBCs were diagnosed in a less favourable stage in 19%, 26% and 23% and less favourable differentiation grade in 22%, 33% and 27% than the PBCs of patients with lobular, lobular mixed and ductal PBC, respectively. In conclusion, lobular and lobular mixed PBC histology are associated with modestly increased CBC risk. Personalised CBC risk assessment needs to consider PBC histology, including systemic treatment administration. The impact on prognosis of CBCs with unfavourable characteristics warrants further evaluation.

Published
2023

31. The predictive ability of the 313 variant–based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant

Author

Lakeman, Inge M. M., Van Den Broek, Alexandra J., Vos, Juliën A. M., Barnes, Daniel R., Adlard, Julian, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Balmaña, Judith, Barrowdale, Daniel, Giraud, Sophie, Golmard, Lisa, Hake, Christopher R., Houdayer, Claude, Risch, Harvey A., Lasset, Christine, Laurent, Maïté, Spurdle, Amanda B., Hooning, Maartje J., Hopper, John L., Kets, Carolien M., Leroux, Dominique, Longy, Michel, Mari, Véronique, Mazoyer, Sylvie, Mebirouk, Noura, Mortemousque, Isabelle, Blok, Marinus J., Prieur, Fabienne, Hamann, Ute, Pujol, Pascal, Konstantopoulou, Irene, Heemskerk Gerritsen, Bernadette A. M., Isaacs, Claudine, Saule, Claire, Piedmonte, Marion, Schuster, Helene, Sevenet, Nicolas, Sobol, Hagay, Sokolowska, Johanna, Gómez Garcia, Encarna B., Venat Bouvet, Laurence, Claes, Kathleen B. M., Ahmed, Munaza, Teixeira, Manuel R., Barwell, Julian, Brady, Angela, Izatt, Louise, Hogervorst, Frans B. L., Brennan, Paul, Harrington, Patricia A., Henderson, Alex, Hodgson, Shirley, Kwong, Ava, Borg, Ake, Kennedy, M. John, Porteous, Mary E., Rogers, Mark T., Side, Lucy E., Snape, Katie, Walker, Lisa, Collée, J. Margriet, Jakubowska, Anna, Couch, Fergus J., Hahnen, Eric, Daly, Mary B., Dennis, Joe, Teo, Soo Hwang, Jensen, Uffe Birk, Rantala, Johanna, Dhawan, Mallika, Benitez, Javier, Domchek, Susan M., Eeles, Ros, Engel, Christoph, Legrand, Clémentine, Evans, D. Gareth, James, Paul A., Feliubadaló i Elorza, Maria Lídia, Teulé-Vega, Àlex, Foretova, Lenka, Castera, Laurent, Friedman, Eitan, Frost, Debra, Rennert, Gad, Ganz, Patricia A., Leslie, Goska, Garber, Judy, Hulick, Peter J., Imyanitov, Evgeny N., Glendon, Gord, Thomassen, Mads, Janavicius, Ramunas, Mulligan, Anna Marie, Hollestelle, Antoinette, Jager, Agnes, Koppert, Linetta B., Cook, Jackie, Koudijs, Marco, Kriege, Mieke, Meijers Heijboer, Hanne E. J., Schmutzler, Rita K., Mensenkamp, Arjen R., Dunning, Alison M., Mooij, Thea M., Oosterwijk, Jan C., Caux Moncoutier, Virginie, Singer, Christian F., Berthet, Pascaline, Caldés, Trinidad, Van den Ouweland, Ans M. W., Van der Baan, Frederieke H., Van der Hout, Annemieke H., Van der Kolk, Lizet E., Van der Luijt, Rob B., Thull, Darcy L., Van Deurzen, Carolien H. M., Sharma, Priyanka, Van Doorn, Helena C., Bignon, Yves Jean, Colas, Chrystelle, Van Engelen, Klaartje, Brewer, Carole, Van Hest, Liselotte P., Van Os, Theo A. M., Caligo, Maria A., Verhoef, Senno, Tischkowitz, Marc, Vogel, Maartje J., Wijnen, Juul T., Lalloo, Fiona, Beesley, Jonathan, Fox, Stephen, Collonge Rame, Marie Agnès, Simard, Jacques, Holland, Helene, Jiao, Yue, John, Esther M., Joseph, Vijai, Gerdes, Anne Marie, Karlan, Beth Y., Lesueur, Fabienne, Loud, Jennifer T., Lubiński, Jan, Manoukian, Siranoush, Mcguffog, Lesley, Miller, Austin, Coupier, Isabelle, Gomes, Denise Molina, Barouk Simonet, Emmanuelle, Montagna, Marco, Miller, Clare, Elan, Camille, Davidson, Rosemarie, Mouret Fourme, Emmanuelle, Gayther, Simon A., Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Pauw, Antoine de, Olah, Edith, Morrison, Patrick J., Olopade, Olufunmilayo I., Van Asperen, Christi J., Park, Sue K., Parsons, Michael T., Donaldson, Alan, Belotti, Muriel, Peterlongo, Paolo, Stadler, Zsofia, Stoppa Lyonnet, Dominique, Sutter, Christian, Ong, Kai Ren, Delnatte, Capucine, Tan, Yen Yen, Toland, Amanda E., Tung, Nadine, Van Rensburg, Elizabeth J., Vega, Ana, Wappenschmidt, Barbara, Devilee, Peter, Eason, Jacqueline, Chung, Wendy K., Bernstein, Jonine L., Offit, Kenneth, Aalfs, Cora M., Hanson, Helen, Godwin, Andrew K., Easton, Douglas F., Bonadona, Valérie, Rookus, Matti A., Chenevix-Trench, Georgia, Antoniou, Antonis C., O’shaughnessy Kirwan, Aoife, Robson, Mark, Eccles, Diana M., Schmidt, Marjanka K., Adank, Muriel A., Gemo Study Collaborators, Phillips, Kelly Anne, Embrace Collaborators, Ocgn Investigators, Goldgar, David E., Hebon Investigators, Perkins, Jo, Kconfab Investigators, Bressac de Paillerets, Brigitte, Buecher, Bruno, Caputo, Sandrine, Ausems, Margreet G. E. M., Gregory, Helen, Caron, Olivier, Faivre, Laurence, Fert Ferrer, Sandra, Gauthier Villars, Marion, Radice, Paolo, Gesta, Paul, Clinical Genetics, Medical Oncology, Surgery, Pathology, Gynecological Oncology, Schmidt, Marjanka K. [0000-0002-2228-429X], Apollo - University of Cambridge Repository, Targeted Gynaecologic Oncology (TARGON), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Schmidt, Marjanka K [0000-0002-2228-429X], HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, Institut Català de la Salut, [Lakeman IMM] Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. [van den Broek AJ, Vos JAM] Division of Molecular Pathology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. [Barnes DR] Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Adlard J] Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, UK. [Andrulis IL] Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. [Balmaña J] Hereditary cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Pediatric surgery, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, CCA - Cancer biology and immunology, Epidemiology and Data Science, Human Genetics, ARD - Amsterdam Reproduction and Development, APH - Personalized Medicine, APH - Quality of Care, Chapel Allerton Hospital, University of Leeds, Departments of Molecular Genetics and Laboratory Medicine and Pathobiology, University of Toronto-Cancer Care Ontario, Reykjavík University, Division of Oncology, Department of Gynaecology and Obstetrics, University Hospital Schleswig–Holstein, The University of Texas M.D. Anderson Cancer Center [Houston], Unitat d'Alt Risc i Prevenció del Càncer, Vall d'Hebron University Hospital [Barcelona], University of Cambridge [UK] (CAM), Group of Human Genetics, Human Cancer Genetics Programme, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Department of Oncology, Clinical Sciences, Lund University [Lund]-Skåne University Hospital, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Section of Genetic Oncology, University of Pisa - Università di Pisa, Columbia University [New York], Ghent University Hospital, Department of Clinical Genetics, Erasmus University Medical Center [Rotterdam] (Erasmus MC)-Family Cancer Clinic, Department of Laboratory Medicine and Pathology, Mayo Clinic, Division of Population Science, Fox Chase Cancer Center, Institut Curie [Paris], Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL), CHU Grenoble, CHI Poissy-Saint-Germain, Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Lab Centraal Lab (9), MUMC+: DA KG Polikliniek (9), and Klinische Genetica

Subjects
0301 basic medicine, Percentile, Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease [DISEASES], Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], SUSCEPTIBILITY ALLELES, Diàtesi, FAMILIES, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], MESH: BRCA2 Protein, Breast cancer, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, Other subheadings::/diagnosis [Other subheadings], Medicine and Health Sciences, Medicine, Mama - Càncer - Diagnòstic, Family history, skin and connective tissue diseases, Genetics (clinical), MESH: Heterozygote, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Factors de risc en les malalties, BRCA1 Protein, Hazard ratio, MESH: Genetic Predisposition to Disease, 1184 Genetics, developmental biology, physiology, article, OVARIAN, BRCA2 Protein/genetics, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 3. Good health, 030220 oncology & carcinogenesis, Female, Malalties congènites, Adult, Heterozygote, medicine.medical_specialty, MESH: Mutation, Risk factors in diseases, Otros calificadores::/diagnóstico [Otros calificadores], Breast Neoplasms, Context (language use), MUTATION CARRIERS, Càncer de mama, afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::susceptibilidad a enfermedades::predisposición genética a la enfermedad [ENFERMEDADES], 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, Humans, Genetic Predisposition to Disease, MESH: BRCA1 Protein, Retrospective Studies, BRCA2 Protein, MESH: Humans, business.industry, Proportional hazards model, CONSORTIUM, Breast Neoplasms/diagnosis, MESH: Adult, MESH: Retrospective Studies, Retrospective cohort study, medicine.disease, Confidence interval, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, BRCA1 Protein/genetics, 3111 Biomedicine, business, MESH: Female, MESH: Breast Neoplasms
Abstract

Predicció de risc de càncer de mama; Dones europees; Variant patògena heterozigota Predicción del riesgo de cáncer de mama; Mujeres europeas; Variante patógena heterocigota Breast cancer risk prediction; European women; Heterozygous pathogenic variant Purpose To evaluate the association between a previously published 313 variant–based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. Methods We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk. Results For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06–1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07–1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC

Published
2021

32. Risk of metachronous contralateral breast cancer in patients with primary invasive lobular breast cancer: Results from a nationwide cohort

Author

Akdeniz, Delal, primary, Kramer, Iris, additional, van Deurzen, Carolien H. M., additional, Heemskerk‐Gerritsen, Bernadette A. M., additional, Schaapveld, Michael, additional, Westenend, Pieter J., additional, Voogd, Adri C., additional, Jager, Agnes, additional, Steyerberg, Ewout W., additional, Sleijfer, Stefan, additional, Schmidt, Marjanka K., additional, and Hooning, Maartje J., additional

Published
2022
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34. External Quality Assessment 2.0: The Importance of a Standardized Implementation of TILs for Daily and Trial Practices

Author

Nauwelaers, Inne, primary, Laudus, Nele, additional, Peeters, Dieter, additional, Acs, Balazs, additional, Denkert, Carsten, additional, Michiels, Stefan, additional, Horlings, Hugo, additional, Siziopikou, Kalliopi P., additional, Ely, Scott, additional, Zardavas, Dimitrios, additional, Mustimbo, Roberts, additional, Bartlett, John, additional, Floris, Giuseppe, additional, Hartman, Johan, additional, van Deurzen, Carolien H. M., additional, Ceusters, Dorien, additional, Dequeker, Els, additional, and Salgado, Roberto, additional

Published
2022
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36. Incorporating progesterone receptor expression into the PREDICT breast prognostic model

Author

Grootes, Isabelle, Keeman, Renske, Blows, Fiona M, Milne, Roger L, Giles, Graham G, Swerdlow, Anthony J, Fasching, Peter A, Abubakar, Mustapha, Andrulis, Irene L, Anton-Culver, Hoda, Beckmann, Matthias W, Blomqvist, Carl, Bojesen, Stig E, Bolla, Manjeet K, Bonanni, Bernardo, Briceno, Ignacio, Burwinkel, Barbara, Camp, Nicola J, Castelao, Jose E, Choi, Ji-Yeob, Clarke, Christine L, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Devilee, Peter, Dörk, Thilo, Dunning, Alison M, Dwek, Miriam, Easton, Douglas F, Eccles, Diana M, Eriksson, Mikael, Ernst, Kristina, Evans, D Gareth, Figueroa, Jonine D, Fink, Visnja, Floris, Giuseppe, Fox, Stephen, Gabrielson, Marike, Gago-Dominguez, Manuela, García-Sáenz, José A, González-Neira, Anna, Haeberle, Lothar, Haiman, Christopher A, Hall, Per, Hamann, Ute, Harkness, Elaine F, Hartman, Mikael, Hooning, Maartje J, van Deurzen, Carolien H M, Garcia-Closas, Montserrat, Pharoah, Paul D.P., Grootes, Isabelle, Keeman, Renske, Blows, Fiona M, Milne, Roger L, Giles, Graham G, Swerdlow, Anthony J, Fasching, Peter A, Abubakar, Mustapha, Andrulis, Irene L, Anton-Culver, Hoda, Beckmann, Matthias W, Blomqvist, Carl, Bojesen, Stig E, Bolla, Manjeet K, Bonanni, Bernardo, Briceno, Ignacio, Burwinkel, Barbara, Camp, Nicola J, Castelao, Jose E, Choi, Ji-Yeob, Clarke, Christine L, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Devilee, Peter, Dörk, Thilo, Dunning, Alison M, Dwek, Miriam, Easton, Douglas F, Eccles, Diana M, Eriksson, Mikael, Ernst, Kristina, Evans, D Gareth, Figueroa, Jonine D, Fink, Visnja, Floris, Giuseppe, Fox, Stephen, Gabrielson, Marike, Gago-Dominguez, Manuela, García-Sáenz, José A, González-Neira, Anna, Haeberle, Lothar, Haiman, Christopher A, Hall, Per, Hamann, Ute, Harkness, Elaine F, Hartman, Mikael, Hooning, Maartje J, van Deurzen, Carolien H M, Garcia-Closas, Montserrat, and Pharoah, Paul D.P.

Abstract

BACKGROUND: Predict Breast (www.predict.nhs.uk) is an online prognostication and treatment benefit tool for early invasive breast cancer. The aim of this study was to incorporate the prognostic effect of progesterone receptor (PR) status into a new version of PREDICT and to compare its performance to the current version (2.2).METHOD: The prognostic effect of PR status was based on the analysis of data from 45,088 European patients with breast cancer from 49 studies in the Breast Cancer Association Consortium. Cox proportional hazard models were used to estimate the hazard ratio for PR status. Data from a New Zealand study of 11,365 patients with early invasive breast cancer were used for external validation. Model calibration and discrimination were used to test the model performance.RESULTS: Having a PR-positive tumour was associated with a 23% and 28% lower risk of dying from breast cancer for women with oestrogen receptor (ER)-negative and ER-positive breast cancer, respectively. The area under the ROC curve increased with the addition of PR status from 0.807 to 0.809 for patients with ER-negative tumours (p = 0.023) and from 0.898 to 0.902 for patients with ER-positive tumours (p = 2.3 × 10-6) in the New Zealand cohort. Model calibration was modest with 940 observed deaths compared to 1151 predicted.CONCLUSION: The inclusion of the prognostic effect of PR status to PREDICT Breast has led to an improvement of model performance and more accurate absolute treatment benefit predictions for individual patients. Further studies should determine whether the baseline hazard function requires recalibration.

Published
2022

37. Functional RECAP (REpair CAPacity) assay identifies homologous recombination deficiency undetected by DNA-based BRCAness tests

Author

CMM Groep Cuppen, Cancer, Pathologie, Meijer, Titia G, Nguyen, Luan, Van Hoeck, Arne, Sieuwerts, Anieta M, Verkaik, Nicole S, Ladan, Marjolijn M, Ruigrok-Ritstier, Kirsten, van Deurzen, Carolien H M, van de Werken, Harmen J G, Lips, Esther H, Linn, Sabine C, Memari, Yasin, Davies, Helen, Nik-Zainal, Serena, Kanaar, Roland, Martens, John W M, Cuppen, Edwin, Jager, Agnes, van Gent, Dik C, CMM Groep Cuppen, Cancer, Pathologie, Meijer, Titia G, Nguyen, Luan, Van Hoeck, Arne, Sieuwerts, Anieta M, Verkaik, Nicole S, Ladan, Marjolijn M, Ruigrok-Ritstier, Kirsten, van Deurzen, Carolien H M, van de Werken, Harmen J G, Lips, Esther H, Linn, Sabine C, Memari, Yasin, Davies, Helen, Nik-Zainal, Serena, Kanaar, Roland, Martens, John W M, Cuppen, Edwin, Jager, Agnes, and van Gent, Dik C

Published
2022

38. Prognostic Value of Stromal Tumor-Infiltrating Lymphocytes in Young, Node-Negative, Triple-Negative Breast Cancer Patients Who Did Not Receive (neo)Adjuvant Systemic Therapy

Author

Pathologie Support, Pathologie Pathologen staf, Cancer, Speerpunt Cancer, Pathologie, Pathologie Opleiding, de Jong, Vincent M T, Wang, Yuwei, Ter Hoeve, Natalie D, Opdam, Mark, Stathonikos, Nikolas, Jóźwiak, Katarzyna, Hauptmann, Michael, Cornelissen, Sten, Vreuls, Willem, Rosenberg, Efraim H, Koop, Esther A, Varga, Zsuzsanna, van Deurzen, Carolien H M, Mooyaart, Antien L, Córdoba, Alicia, Groen, Emma J, Bart, Joost, Willems, Stefan M, Zolota, Vasiliki, Wesseling, Jelle, Sapino, Anna, Chmielik, Ewa, Ryska, Ales, Broeks, Annegien, Voogd, Adri C, Loi, Sherene, Michiels, Stefan, Sonke, Gabe S, van der Wall, Elsken, Siesling, Sabine, van Diest, Paul J, Schmidt, Marjanka K, Kok, Marleen, Dackus, Gwen M H E, Salgado, Roberto, Linn, Sabine C, Pathologie Support, Pathologie Pathologen staf, Cancer, Speerpunt Cancer, Pathologie, Pathologie Opleiding, de Jong, Vincent M T, Wang, Yuwei, Ter Hoeve, Natalie D, Opdam, Mark, Stathonikos, Nikolas, Jóźwiak, Katarzyna, Hauptmann, Michael, Cornelissen, Sten, Vreuls, Willem, Rosenberg, Efraim H, Koop, Esther A, Varga, Zsuzsanna, van Deurzen, Carolien H M, Mooyaart, Antien L, Córdoba, Alicia, Groen, Emma J, Bart, Joost, Willems, Stefan M, Zolota, Vasiliki, Wesseling, Jelle, Sapino, Anna, Chmielik, Ewa, Ryska, Ales, Broeks, Annegien, Voogd, Adri C, Loi, Sherene, Michiels, Stefan, Sonke, Gabe S, van der Wall, Elsken, Siesling, Sabine, van Diest, Paul J, Schmidt, Marjanka K, Kok, Marleen, Dackus, Gwen M H E, Salgado, Roberto, and Linn, Sabine C

Published
2022

39. Additional file 4 of Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author

Ahearn, Thomas U., Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L., Bolla, Manjeet K., Dennis, Joe, Dunning, Alison M., Lush, Michael, Wang, Qin, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Auer, Paul L., Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, B��rresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Br��ning, Thomas, Burwinkel, Barbara, Buys, Saundra S., Canzian, Federico, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Clarke, Christine L., Coll��e, J. Margriet, Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, D��rk, Thilo, Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M., Garc��a-S��enz, Jos�� A., Gaudet, Mia M., Giles, Graham G., Goldberg, Mark S., Gonz��lez-Neira, Anna, Aln��s, Grethe I. Grenaker, Grip, Mervi, Gu��nel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N., Kr��ger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W., Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G., Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G., Nodora, Jesse, Offit, Kenneth, Olsson, H��kan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa V., Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylk��s, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, R��diger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Schmutzler, Rita K., Schoemaker, Minouk J., Sch��ttker, Ben, Sherman, Mark E., Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C., Spinelli, John J., Swerdlow, Anthony J., Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teras, Lauren R., Terry, Mary Beth, Torres, Diana, Troester, Melissa A., Vachon, Celine M., van Deurzen, Carolien H. M., van Veen, Elke M., Wagner, Philippe, Weinberg, Clarice R., Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Zheng, Wei, Couch, Fergus J., Simard, Jacques, Kraft, Peter, Easton, Douglas F., Pharoah, Paul D. P., Schmidt, Marjanka K., Garc��a-Closas, Montserrat, and Chatterjee, Nilanjan

Subjects
Data_FILES
Abstract

Additional file 4. Funding and Acknowledgement. This file contains the additional funding not included in the main text, the acknowledgments, and the names of the people in the collaboration groups.

Published
2022
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40. Prognostic Value of Stromal Tumor-Infiltrating Lymphocytes in Young, Node-Negative, Triple-Negative Breast Cancer Patients Who Did Not Receive (neo)Adjuvant Systemic Therapy

Author

de Jong, Vincent M T, Wang, Yuwei, Ter Hoeve, Natalie D, Opdam, Mark, Stathonikos, Nikolas, Jóźwiak, Katarzyna, Hauptmann, Michael, Cornelissen, Sten, Vreuls, Willem, Rosenberg, Efraim H, Koop, Esther A, Varga, Zsuzsanna, van Deurzen, Carolien H M, Mooyaart, Antien L, Córdoba, Alicia, Groen, Emma J, Bart, Joost, Willems, Stefan M, Zolota, Vasiliki, Wesseling, Jelle, Sapino, Anna, Chmielik, Ewa, Ryska, Ales, Broeks, Annegien, Voogd, Adri C, Loi, Sherene, Michiels, Stefan, Sonke, Gabe S, van der Wall, Elsken, Siesling, Sabine, et al, and University of Zurich

Subjects
10049 Institute of Pathology and Molecular Pathology, 610 Medicine & health
Published
2022
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43. Risk of metachronous contralateral breast cancer in patients with primary invasive lobular breast cancer: Results from a nationwide cohort.

Author

Akdeniz, Delal, Kramer, Iris, van Deurzen, Carolien H. M., Heemskerk‐Gerritsen, Bernadette A. M., Schaapveld, Michael, Westenend, Pieter J., Voogd, Adri C., Jager, Agnes, Steyerberg, Ewout W., Sleijfer, Stefan, Schmidt, Marjanka K., and Hooning, Maartje J.

Subjects
LOBULAR carcinoma, CANCER patients, BREAST cancer, HORMONE therapy, COMPETING risks
Abstract

Lobular primary breast cancer (PBC) histology has been proposed as a risk factor for contralateral breast cancer (CBC), but results have been inconsistent. We investigated CBC risk and the impact of systemic therapy in lobular versus ductal PBC. Further, CBC characteristics following these histologic subtypes were explored. We selected 74,373 women diagnosed between 2003 and 2010 with stage I‐III invasive PBC from the nationwide Netherlands Cancer Registry. We assessed absolute risk of CBC taking into account competing risks among those with lobular (n = 8903), lobular mixed with other types (n = 3512), versus ductal (n = 62,230) histology. Hazard ratios (HR) for CBC were estimated in a cause‐specific Cox model, adjusting for age at PBC diagnosis, radiotherapy, chemotherapy and/or endocrine therapy. Multivariable HRs for CBC were 1.18 (95% CI: 1.04–1.33) for lobular and 1.37 (95% CI: 1.16–1.63) for lobular mixed versus ductal PBC. Ten‐year cumulative CBC incidences in patients with lobular, lobular mixed versus ductal PBC were 3.2%, 3.6% versus 2.8% when treated with systemic therapy and 6.6%, 7.7% versus 5.6% in patients without systemic therapy, respectively. Metachronous CBCs were diagnosed in a less favourable stage in 19%, 26% and 23% and less favourable differentiation grade in 22%, 33% and 27% than the PBCs of patients with lobular, lobular mixed and ductal PBC, respectively. In conclusion, lobular and lobular mixed PBC histology are associated with modestly increased CBC risk. Personalised CBC risk assessment needs to consider PBC histology, including systemic treatment administration. The impact on prognosis of CBCs with unfavourable characteristics warrants further evaluation. [ABSTRACT FROM AUTHOR]

Published
2023
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45. Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group

Author

Van Bockstal, Mieke R., primary, Cooks, Maxine, additional, Nederlof, Iris, additional, Brinkhuis, Mariël, additional, Dutman, Annemiek, additional, Koopmans, Monique, additional, Kooreman, Loes, additional, van der Vegt, Bert, additional, Verhoog, Leon, additional, Vreuls, Celine, additional, Westenend, Pieter, additional, Kok, Marleen, additional, van Diest, Paul J., additional, Nauwelaers, Inne, additional, Laudus, Nele, additional, Denkert, Carsten, additional, Rimm, David, additional, Siziopikou, Kalliopi P., additional, Ely, Scott, additional, Zardavas, Dimitrios, additional, Roberts, Mustimbo, additional, Floris, Giuseppe, additional, Hartman, Johan, additional, Acs, Balazs, additional, Peeters, Dieter, additional, Bartlett, John M.S., additional, Dequeker, Els, additional, Salgado, Roberto, additional, Giudici, Fabiola, additional, Michiels, Stefan, additional, Horlings, Hugo, additional, and van Deurzen, Carolien H. M., additional

Published
2021
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46. Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2

Author

Orr, Nick, Dudbridge, Frank, Dryden, Nicola, Maguire, Sarah, Novo, Daniela, Perrakis, Eleni, Johnson, Nichola, Ghoussaini, Maya, Hopper, John L., Southey, Melissa C., Apicella, Carmel, Stone, Jennifer, Schmidt, Marjanka K., Broeks, Annegien, Vanʼt Veer, Laura J., Hogervorst, Frans B., Fasching, Peter A., Haeberle, Lothar, Ekici, Arif B., Beckmann, Matthias W., Gibson, Lorna, Aitken, Zoe, Warren, Helen, Sawyer, Elinor, Tomlinson, Ian, Kerin, Michael J., Miller, Nicola, Burwinkel, Barbara, Marme, Frederik, Schneeweiss, Andreas, Sohn, Chistof, Guénel, Pascal, Truong, Thérèse, Cordina-Duverger, Emilie, Sanchez, Marie, Bojesen, Stig E., Nordestgaard, Børge G., Nielsen, Sune F., Flyger, Henrik, Benitez, Javier, Zamora, Maria Pilar, Arias Perez, Jose Ignacio, Menéndez, Primitiva, Anton-Culver, Hoda, Neuhausen, Susan L., Brenner, Hermann, Dieffenbach, Aida Karina, Arndt, Volker, Stegmaier, Christa, Hamann, Ute, Brauch, Hiltrud, Justenhoven, Christina, Brüning, Thomas, Ko, Yon-Dschun, Nevanlinna, Heli, Aittomäki, Kristiina, Blomqvist, Carl, Khan, Sofia, Bogdanova, Natalia, Dörk, Thilo, Lindblom, Annika, Margolin, Sara, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M., Chenevix-Trench, Georgia, Beesley, Jonathan, Lambrechts, Diether, Moisse, Matthieu, Floris, Guiseppe, Beuselinck, Benoit, Chang-Claude, Jenny, Rudolph, Anja, Seibold, Petra, Flesch-Janys, Dieter, Radice, Paolo, Peterlongo, Paolo, Peissel, Bernard, Pensotti, Valeria, Couch, Fergus J., Olson, Janet E., Slettedahl, Seth, Vachon, Celine, Giles, Graham G., Milne, Roger L., McLean, Catriona, Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick, Le Marchand, Loic, Simard, Jacques, Goldberg, Mark S., Labrèche, France, Dumont, Martine, Kristensen, Vessela, Alnæs, Grethe Grenaker, Nord, Silje, Borresen-Dale, Anne-Lise, Zheng, Wei, Deming-Halverson, Sandra, Shrubsole, Martha, Long, Jirong, Winqvist, Robert, Pylkäs, Katri, Jukkola-Vuorinen, Arja, Grip, Mervi, Andrulis, Irene L., Knight, Julia A., Glendon, Gord, Tchatchou, Sandrine, Devilee, Peter, Tollenaar, Robertus A. E. M., Seynaeve, Caroline M., Van Asperen, Christi J., Garcia-Closas, Montserrat, Figueroa, Jonine, Chanock, Stephen J., Lissowska, Jolanta, Czene, Kamila, Darabi, Hatef, Eriksson, Mikael, Klevebring, Daniel, Hooning, Maartje J., Hollestelle, Antoinette, van Deurzen, Carolien H. M., Kriege, Mieke, Hall, Per, Li, Jingmei, Liu, Jianjun, Humphreys, Keith, Cox, Angela, Cross, Simon S., Reed, Malcolm W. R., Pharoah, Paul D. P., Dunning, Alison M., Shah, Mitul, Perkins, Barbara J., Jakubowska, Anna, Lubinski, Jan, Jaworska-Bieniek, Katarzyna, Durda, Katarzyna, Ashworth, Alan, Swerdlow, Anthony, Jones, Michael, Schoemaker, Minouk J., Meindl, Alfons, Schmutzler, Rita K., Olswold, Curtis, Slager, Susan, Toland, Amanda E., Yannoukakos, Drakoulis, Muir, Kenneth, Lophatananon, Artitaya, Stewart-Brown, Sarah, Siriwanarangsan, Pornthep, Matsuo, Keitaro, Ito, Hidema, Iwata, Hiroji, Ishiguro, Junko, Wu, Anna H., Tseng, Chiu-chen, Van Den Berg, David, Stram, Daniel O., Teo, Soo Hwang, Yip, Cheng Har, Kang, Peter, Ikram, Mohammad Kamran, Shu, Xiao-Ou, Lu, Wei, Gao, Yu-Tang, Cai, Hui, Kang, Daehee, Choi, Ji-Yeob, Park, Sue K., Noh, Dong-Young, Hartman, Mikael, Miao, Hui, Lim, Wei Yen, Lee, Soo Chin, Sangrajrang, Suleeporn, Gaborieau, Valerie, Brennan, Paul, Mckay, James, Wu, Pei-Ei, Hou, Ming-Feng, Yu, Jyh-Cherng, Shen, Chen-Yang, Blot, William, Cai, Qiuyin, Signorello, Lisa B., Luccarini, Craig, Bayes, Caroline, Ahmed, Shahana, Maranian, Mel, Healey, Catherine S., González-Neira, Anna, Pita, Guillermo, Alonso, M. Rosario, Álvarez, Nuria, Herrero, Daniel, Tessier, Daniel C., Vincent, Daniel, Bacot, Francois, Hunter, David J., Lindstrom, Sara, Dennis, Joe, Michailidou, Kyriaki, Bolla, Manjeet K., Easton, Douglas F., dos Santos Silva, Isabel, Fletcher, Olivia, and Peto, Julian

Published
2015
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47. Transcriptomic Properties of HER2+ Ductal Carcinoma In Situ of the Breast Associate with Absence of Immune Cells

Author

Agahozo, Marie Colombe, primary, Smid, Marcel, additional, van Marion, Ronald, additional, Hammerl, Dora, additional, van den Bosch, Thierry P. P., additional, Timmermans, Mieke A. M., additional, Heijerman, Chayenne J., additional, Westenend, Pieter J., additional, Debets, Reno, additional, Martens, John W. M., additional, and van Deurzen, Carolien H. M., additional

Published
2021
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48. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Author

Coignard, Juliette, Lush, Michael, Beesley, Jonathan, O’Mara, Tracy A., Dennis, Joe, Tyrer, Jonathan P., Barnes, Daniel R., McGuffog, Lesley, Leslie, Goska, Bolla, Manjeet K., Adank, Muriel A., Agata, Simona, Ahearn, Thomas, Aittomäki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Arun, Banu K., Augustinsson, Annelie, Azzollini, Jacopo, Barrowdale, Daniel, Baynes, Caroline, Becher, Heko, Bermisheva, Marina, Bernstein, Leslie, Białkowska, Katarzyna, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S., Caldés, Trinidad, Caligo, Maria A., Campa, Daniele, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Bertrand, Ophélie, Caputo, Sandrine, Dupré, Anaïs, le Mentec, Marine, Belotti, Muriel, Birot, Anne-Marie, Buecher, Bruno, Fourme, Emmanuelle, Gauthier-Villars, Marion, Golmard, Lisa, Houdayer, Claude, Moncoutier, Virginie, de Pauw, Antoine, Saule, Claire, Sinilnikova, Olga, Mazoyer, Sylvie, Damiola, Francesca, Barjhoux, Laure, Verny-Pierre, Carole, Léone, M. lanie, Boutry-Kryza, Nadia, Calender, Alain, Giraud, Sophie, Caron, Olivier, Guillaud-Bataille, Marine, Bressac-de-Paillerets, Brigitte, Bignon, Yves- Jean, Uhrhammer, Nancy, Lasset, Christine, Bonadona, Valérie, Berthet, Pascaline, Vaur, Dominique, Castera, Laurent, Noguchi, Tetsuro, Popovici, Cornel, Sobol, Hagay, Bourdon, Violaine, Remenieras, Audrey, Noguès, Catherine, Coupier, Isabelle, Pujol, Pascal, Dumont, Aurélie, Révillion, Françoise, Adenis, Claude, Muller, Danièle, Barouk-Simonet, Emmanuelle, Bonnet, Françoise, Bubien, Virginie, Sevenet, Nicolas, Longy, Michel, Toulas, Christine, Guimbaud, Rosine, Gladieff, Laurence, Feillel, Viviane, Leroux, Dominique, Dreyfus, H. lène, Rebischung, Christine, Peysselon, Magalie, Coron, Fanny, Faivre, Laurence, Baurand, Amandine, Jacquot, Caroline, Bertolone, Geoffrey, Lizard, Sarab, Prieur, Fabienne, Lebrun, Marine, Kientz, Caroline, Ferrer, Sandra Fert, Mari, V. ronique, Vénat-Bouvet, Laurence, Delnatte, Capucine, Bézieau, Stéphane, Mortemousque, Isabelle, Coulet, Florence, Colas, Chrystelle, Soubrier, Florent, Warcoin, Mathilde, Sokolowska, Johanna, Bronner, Myriam, Collonge-Rame, Marie-Agnès, Damette, Alexandre, Gesta, Paul, Lallaoui, Hakima, Chiesa, Jean, Molina-Gomes, Denise, Ingster, Olivier, Gregory, Helen, Miedzybrodzka, Zosia, Morrison, Patrick J., Ong, Kai-ren, Donaldson, Alan, Rogers, Mark T., Kennedy, M. John, Porteous, Mary E., Brewer, Carole, Davidson, Rosemarie, Izatt, Louise, Brady, Angela, Barwell, Julian, Adlard, Julian, Foo, Claire, Lalloo, Fiona, Side, Lucy E., Eason, Jacqueline, Henderson, Alex, Walker, Lisa, Eeles, Rosalind A., Cook, Jackie, Snape, Katie, Eccles, Diana, Murray, Alex, McCann, Emma, Collée, J. Margriet, Conroy, Don M., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Dörk, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Barberan, Vanesa, García-Closas, Montserrat, García-Sáenz, José A., Gaudet, Mia M., Gayther, Simon A., Gehrig, Andrea, Georgoulias, Vassilios, Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., González-Neira, Anna, Greene, Mark H., Guénel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Håkansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., He, Wei, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hopper, John L., Horcasitas, Darling J., Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Fox, Stephen, Campbell, Ian, Spurdle, Amanda, Webb, Penny, de Fazio, Anna, Tassell, Margaret, Kirk, Judy, Lindeman, Geoff, Price, Melanie, Southey, Melissa, Milne, Roger, Deb, Sid, Bowtell, David, van der Hout, Annemieke H., van den Ouweland, Ans M. W., Mensenkamp, Arjen R., van Deurzen, Carolien H. M., Kets, Carolien M., Seynaeve, Caroline, van Asperen, Christi J., Aalfs, Cora M., Gómez Garcia, Encarna B., van Leeuwen, Flora E., de Bock, G. H., Meijers-Heijboer, Hanne E. J., Obdeijn, Inge M., Gille, J. J. P., Oosterwijk, Jan C., Wijnen, Juul T., van der Kolk, Lizet E., Hooning, Maartje J., Ausems, Margreet G. E. M., Mourits, Marian J. E., Blok, Marinus J., Rookus, Matti A., van der Luijt, Rob B., van Cronenburg, T. C. T. E. F., van der Pol, Carmen C., Russell, Nicola S., Siesling, Sabine, Overbeek, Lucy, Wijnands, R., de Lange, Judith L., Clarke, Christine, Graham, Dinny, Sachchithananthan, Mythily, Marsh, Deborah, Scott, Rodney, Baxter, Robert, Yip, Desmond, Carpenter, Jane, Davis, Alison, Pathmanathan, Nirmala, Simpson, Peter, Jager, Agnes, Jakubowska, Anna, James, Paul A., Jensen, Uffe Birk, John, Esther M., Jones, Michael E., Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khusnutdinova, Elza, Kiiski, Johanna I., Ko, Yon-Dschun, Kosma, Veli-Matti, Kraft, Peter, Kurian, Allison W., Laitman, Yael, Lambrechts, Diether, le Marchand, Loic, Lester, Jenny, Lesueur, Fabienne, Lindstrom, Tricia, Lopez-Fernández, Adria, Loud, Jennifer T., Luccarini, Craig, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Milne, Roger L., Montagna, Marco, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nielsen, Finn C., O’Brien, Katie M., Olopade, Olufunmilayo I., Olson, Janet E., Olsson, H. kan, Osorio, Ana, Ottini, Laura, Park-Simon, Tjoung-Won, Parsons, Michael T., Pedersen, Inge Sokilde, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P., Phillips, Kelly-Anne, Polley, Eric C., Poppe, Bruce, Presneau, Nadege, Pujana, Miquel Angel, Punie, Kevin, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Robson, Mark, Romero, Atocha, Rossing, Maria, Saloustros, Emmanouil, Sandler, Dale P., Santella, Regina, Scheuner, Maren T., Schmidt, Marjanka K., Schmidt, Gunnar, Scott, Christopher, Sharma, Priyanka, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Steinsnyder, Zoe, Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Terry, Mary Beth, Teulé, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Trainer, Alison H., Truong, Thérèse, Tung, Nadine, Vachon, Celine M., Vega, Ana, Vijai, Joseph, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wendt, Camilla, Wolk, Alicja, Yadav, Siddhartha, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Park, Sue K., Thomassen, Mads, Offit, Kenneth, Schmutzler, Rita K., Couch, Fergus J., Simard, Jacques, Chenevix-Trench, Georgia, Easton, Douglas F., Andrieu, Nadine, Antoniou, Antonis C., German Cancer Research Center, National Health and Medical Research Council (Australia), United States of Department of Health & Human Services, National Institute for Health Research (Reino Unido), French National Cancer Institute, Ligue Nationale Contre le Cancer (Francia), Cancer Research UK (Reino Unido), Unión Europea. Comisión Europea, Canadian Institutes of Health Research, Cancer Council New South Wales (Australia), KWF Kankerbestrijding, Instituto de Salud Carlos III, Xunta de Galicia (España), Ministerio de Sanidad, Política Social e Igualdad (España), Helmholtz Association, California Breast Cancer Research Program, Federal Ministry of Education & Research (Alemania), Government of Netherlands, Russian Foundation for Basic Research, O’Mara, Tracy A. [0000-0002-5436-3232], Dennis, Joe [0000-0003-4591-1214], Tyrer, Jonathan P. [0000-0003-3724-4757], Barnes, Daniel R. [0000-0002-3781-7570], Leslie, Goska [0000-0001-5756-6222], Ahearn, Thomas [0000-0003-0771-7752], Andrulis, Irene L. [0000-0002-4226-6435], Arndt, Volker [0000-0001-9320-8684], Azzollini, Jacopo [0000-0002-9364-9778], Barrowdale, Daniel [0000-0003-1661-3939], Becher, Heko [0000-0002-8808-6667], Bernstein, Leslie [0000-0002-7692-6518], Bojesen, Stig E. [0000-0002-4061-4133], Bonanni, Bernardo [0000-0003-3589-2128], Brauch, Hiltrud [0000-0001-7531-2736], Caldés, Trinidad [0000-0002-1038-5392], Chanock, Stephen J. [0000-0002-2324-3393], Chung, Wendy K. [0000-0003-3438-5685], Claes, Kathleen B. M. [0000-0003-0841-7372], Collée, J. Margriet [0000-0002-9272-9346], Devilee, Peter [0000-0002-8023-2009], Dörk, Thilo [0000-0002-9458-0282], Dunning, Alison M. [0000-0001-6651-7166], Dwek, Miriam [0000-0001-7184-2932], Eliassen, A. Heather [0000-0002-3961-6609], Fritschi, Lin [0000-0002-7692-3560], García-Closas, Montserrat [0000-0003-1033-2650], García-Sáenz, José A. [0000-0001-6880-0301], Gayther, Simon A. [0000-0001-7937-5443], Giles, Graham G. [0000-0003-4946-9099], Greene, Mark H. [0000-0003-1852-9239], Guénel, Pascal [0000-0002-8359-518X], Håkansson, Niclas [0000-0001-7673-5554], Hart, Steven N. [0000-0001-7714-2734], He, Wei [0000-0003-0161-3274], Hollestelle, Antoinette [0000-0003-1166-1966], Hulick, Peter J. [0000-0001-8397-4078], Jakubowska, Anna [0000-0002-5650-0501], James, Paul A. [0000-0002-4361-4657], Jensen, Uffe Birk [0000-0002-6205-6355], Jones, Michael E. [0000-0001-7479-3451], Kapoor, Pooja Middha [0000-0001-5503-8215], Keeman, Renske [0000-0002-5452-9933], Kraft, Peter [0000-0002-4472-8103], Kurian, Allison W. [0000-0002-6175-9470], Lambrechts, Diether [0000-0002-3429-302X], Lesueur, Fabienne [0000-0001-7404-4549], Martens, John W. M. [0000-0002-3428-3366], Miller, Austin [0000-0001-9739-8462], Milne, Roger L. [0000-0001-5764-7268], Nathanson, Katherine L. [0000-0002-6740-0901], Nevanlinna, Heli [0000-0002-0916-2976], Olopade, Olufunmilayo I. [0000-0002-9936-1599], Olson, Janet E. [0000-0003-4944-7789], Ottini, Laura [0000-0001-8030-0449], Parsons, Michael T. [0000-0003-3242-8477], Pedersen, Inge Sokilde [0000-0002-9902-8040], Peshkin, Beth [0000-0002-2997-4701], Peterlongo, Paolo [0000-0001-6951-6855], Peto, Julian [0000-0002-1685-8912], Pharoah, Paul D. P. [0000-0001-8494-732X], Punie, Kevin [0000-0002-1162-7963], Radice, Paolo [0000-0001-6298-4111], Rennert, Gad [0000-0002-8512-068X], Robson, Mark [0000-0002-3109-1692], Romero, Atocha [0000-0002-1634-7397], Saloustros, Emmanouil [0000-0002-0485-0120], Sandler, Dale P. [0000-0002-6776-0018], Schmidt, Marjanka K. [0000-0002-2228-429X], Scott, Christopher [0000-0003-1340-0647], Stone, Jennifer [0000-0001-5077-0124], Toland, Amanda E. [0000-0002-0271-1792], Truong, Thérèse [0000-0002-2943-6786], Vachon, Celine M. [0000-0002-1962-9322], Vega, Ana [0000-0002-7416-5137], Vijai, Joseph [0000-0002-7933-151X], Weitzel, Jeffrey N. [0000-0001-6714-092X], Wolk, Alicja [0000-0001-7387-6845], Yadav, Siddhartha [0000-0003-4630-9903], Yannoukakos, Drakoulis [0000-0001-7509-3510], Ziogas, Argyrios [0000-0003-4529-3727], Zorn, Kristin K. [0000-0003-2143-8979], Park, Sue K. [0000-0001-5002-9707], Simard, Jacques [0000-0001-6906-3390], Easton, Douglas F. [0000-0003-2444-3247], Apollo - University of Cambridge Repository, Becher, Heiko [0000-0002-8808-6667], RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), Klinische Genetica, German Cancer Research Center (DKFZ), National Health and Medical Research Council of Australia, United States Department of Health & Human Services National Institutes of Health (NIH) - USA, National Institute for Health Research (NIHR), Institut National du Cancer (INCA) France, Ligue nationale contre le cancer, Cancer Research UK, European Commision, Canadian Institutes of Health Research (CIHR), Cancer Council New South Wales, Accion Estrategica de Salud del Instituto de Salud Carlos III FIS Intrasalud, Xunta de Galicia, Fomento de la Investigacion Clinica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain, Fondo de Investigacion Sanitario, California Breast Cancer Research Fund, Federal Ministry of Education & Research (BMBF), Netherlands Government, Russian Foundation for Basic Research (RFBR), O'Mara, Tracy A [0000-0002-5436-3232], Tyrer, Jonathan P [0000-0003-3724-4757], Barnes, Daniel R [0000-0002-3781-7570], Andrulis, Irene L [0000-0002-4226-6435], Bojesen, Stig E [0000-0002-4061-4133], Chanock, Stephen J [0000-0002-2324-3393], Chung, Wendy K [0000-0003-3438-5685], Claes, Kathleen BM [0000-0003-0841-7372], Collée, J Margriet [0000-0002-9272-9346], Dunning, Alison M [0000-0001-6651-7166], Eliassen, A Heather [0000-0002-3961-6609], García-Sáenz, José A [0000-0001-6880-0301], Gayther, Simon A [0000-0001-7937-5443], Giles, Graham G [0000-0003-4946-9099], Greene, Mark H [0000-0003-1852-9239], Hart, Steven N [0000-0001-7714-2734], Hulick, Peter J [0000-0001-8397-4078], James, Paul A [0000-0002-4361-4657], Jones, Michael E [0000-0001-7479-3451], Kurian, Allison W [0000-0002-6175-9470], Martens, John WM [0000-0002-3428-3366], Milne, Roger L [0000-0001-5764-7268], Nathanson, Katherine L [0000-0002-6740-0901], Olopade, Olufunmilayo I [0000-0002-9936-1599], Olson, Janet E [0000-0003-4944-7789], Parsons, Michael T [0000-0003-3242-8477], Pharoah, Paul DP [0000-0001-8494-732X], Sandler, Dale P [0000-0002-6776-0018], Schmidt, Marjanka K [0000-0002-2228-429X], Toland, Amanda E [0000-0002-0271-1792], Vachon, Celine M [0000-0002-1962-9322], Weitzel, Jeffrey N [0000-0001-6714-092X], Zorn, Kristin K [0000-0003-2143-8979], Park, Sue K [0000-0001-5002-9707], Easton, Douglas F [0000-0003-2444-3247], HUS Comprehensive Cancer Center, Department of Oncology, Clinicum, INDIVIDRUG - Individualized Drug Therapy, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, Institut Català de la Salut, [Coignard J] Genetic Epidemiology of Cancer team, Inserm, U900, Paris, France. Institut Curie Paris, Paris, France. Mines ParisTech Fontainebleau, Paris, France. Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. PSL University Paris, Paris, France. Paris Sud University, Orsay, France. [Lush M, Dennis J] Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Beesley J, O'Mara TA] Department of Genetics and Computational Biology QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. [Tyrer JP] Centre for Cancer Genetic Epidemiology, Department of Oncology University of Cambridge, Cambridge, UK. [Diez O] Oncogenetics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Àrea de Genètica Clínica i Molecular, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Lopez-Fernández A] High Risk and Cancer Prevention Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Life Course Epidemiology (LCE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Human Genetics, ARD - Amsterdam Reproduction and Development, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, CCA - Cancer biology and immunology, Clinical Genetics, Medical Oncology, Pathology, and Radiology & Nuclear Medicine

Subjects
0301 basic medicine, Linkage disequilibrium, endocrine system diseases, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], 45/43, General Physics and Astronomy, Genome-wide association study, Linkage Disequilibrium, Breast cancer, 0302 clinical medicine, 3123 Gynaecology and paediatrics, Risk Factors, Genotype, breast neoplasms, Medicine and Health Sciences, 631/208/68, skin and connective tissue diseases, Cancer genetics, adult, alleles, BRCA1 protein, BRCA2 protein, female, genetic predisposition to disease, genome-wide association study, genotype, humans, linkage disequilibrium, middle aged, mutation, quantitative trait loci, risk factors, polymorphism, single nucleotide, HEBON Investigators, Genetics, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], education.field_of_study, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Multidisciplinary, Otros calificadores::Otros calificadores::/genética [Otros calificadores], BRCA1 Protein, Genetic Predisposition to Disease/genetics, article, Single Nucleotide, Middle Aged, BRCA2 Protein/genetics, 3. Good health, Mama - Càncer - Factors de risc, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Genome-Wide Association Study/methods, Medical genetics, Female, Medical Genetics, 692/499, Adult, medicine.medical_specialty, 45/61, Science, 3122 Cancers, Population, Quantitative Trait Loci, Genetic Phenomena::Genetic Variation::Mutation [PHENOMENA AND PROCESSES], ABCTB Investigators, 631/67/2324, Breast Neoplasms, Biology, Breast Neoplasms/genetics, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Càncer de mama, GEMO Study Collaborators, 03 medical and health sciences, Cancer epidemiology, SDG 3 - Good Health and Well-being, Other subheadings::Other subheadings::/genetics [Other subheadings], medicine, Humans, Genetic Predisposition to Disease, Allele, Polymorphism, education, EMBRACE Collaborators, fenómenos genéticos::variación genética::mutación [FENÓMENOS Y PROCESOS], Alleles, Medicinsk genetik, BRCA2 Protein, Mutació (Biologia), General Chemistry, 631/67/1347, Genotype frequency, 030104 developmental biology, Mutation, Mama - Càncer - Aspectes genètics, BRCA1 Protein/genetics, 3111 Biomedicine, KConFab Investigators, Quantitative Trait Loci/genetics, Genètica, Genome-Wide Association Study
Abstract

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P, Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

Published
2021

49. Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study.

Author

UCL - (MGD) Service d'anatomie pathologique, UCL - SSS/IREC/MONT - Pôle Mont Godinne, Van Bockstal, Mieke R, François, Aline, Altinay, Serdar, Arnould, Laurent, Balkenhol, Maschenka, Broeckx, Glenn, Burguès, Octavio, Colpaert, Cecile, Dedeurwaerdere, Franceska, Dessauvagie, Benjamin, Duwel, Valérie, Floris, Giuseppe, Fox, Stephen, Gerosa, Clara, Hastir, Delfyne, Jaffer, Shabnam, Kurpershoek, Eline, Lacroix-Triki, Magali, Laka, Andoni, Lambein, Kathleen, MacGrogan, Gaëtan Marie, Marchiò, Caterina, Martin Martinez, Maria-Dolores, Nofech-Mozes, Sharon, Peeters, Dieter, Ravarino, Alberto, Reisenbichler, Emily, Resetkova, Erika, Sanati, Souzan, Schelfhout, Anne-Marie, Schelfhout, Vera, Shaaban, Abeer, Sinke, Renata, Stanciu-Pop, Claudia, van Deurzen, Carolien H M, Van de Vijver, Koen K, Van Rompuy, Anne-Sophie, Vincent-Salomon, Anne, Wen, Hannah Y, Wong, Serena, Bouzin, Caroline, Galant, Christine, UCL - (MGD) Service d'anatomie pathologique, UCL - SSS/IREC/MONT - Pôle Mont Godinne, Van Bockstal, Mieke R, François, Aline, Altinay, Serdar, Arnould, Laurent, Balkenhol, Maschenka, Broeckx, Glenn, Burguès, Octavio, Colpaert, Cecile, Dedeurwaerdere, Franceska, Dessauvagie, Benjamin, Duwel, Valérie, Floris, Giuseppe, Fox, Stephen, Gerosa, Clara, Hastir, Delfyne, Jaffer, Shabnam, Kurpershoek, Eline, Lacroix-Triki, Magali, Laka, Andoni, Lambein, Kathleen, MacGrogan, Gaëtan Marie, Marchiò, Caterina, Martin Martinez, Maria-Dolores, Nofech-Mozes, Sharon, Peeters, Dieter, Ravarino, Alberto, Reisenbichler, Emily, Resetkova, Erika, Sanati, Souzan, Schelfhout, Anne-Marie, Schelfhout, Vera, Shaaban, Abeer, Sinke, Renata, Stanciu-Pop, Claudia, van Deurzen, Carolien H M, Van de Vijver, Koen K, Van Rompuy, Anne-Sophie, Vincent-Salomon, Anne, Wen, Hannah Y, Wong, Serena, Bouzin, Caroline, and Galant, Christine

Abstract

High stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC) are associated with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Histopathological assessment of sTILs in TNBC biopsies is characterized by substantial interobserver variability, but it is unknown whether this affects its association with pCR. Here, we aimed to investigate the degree of interobserver variability in an international study, and its impact on the relationship between sTILs and pCR. Forty pathologists assessed sTILs as a percentage in digitalized biopsy slides, originating from 41 TNBC patients who were treated with NAC followed by surgery. Pathological response was quantified by the MD Anderson Residual Cancer Burden (RCB) score. Intraclass correlation coefficients (ICCs) were calculated per pathologist duo and Bland-Altman plots were constructed. The relation between sTILs and pCR or RCB class was investigated. The ICCs ranged from -0.376 to 0.947 (mean: 0.659), indicating substantial interobserver variability. Nevertheless, high sTILs scores were significantly associated with pCR for 36 participants (90%), and with RCB class for eight participants (20%). Post hoc sTILs cutoffs at 20% and 40% resulted in variable associations with pCR. The sTILs in TNBC with RCB-II and RCB-III were intermediate to those of RCB-0 and RCB-I, with lowest sTILs observed in RCB-I. However, the limited number of RCB-I cases precludes any definite conclusions due to lack of power, and this observation therefore requires further investigation. In conclusion, sTILs are a robust marker for pCR at the group level. However, if sTILs are to be used to guide the NAC scheme for individual patients, the observed interobserver variability might substantially affect the chance of obtaining a pCR. Future studies should determine the 'ideal' sTILs threshold, and attempt to fine-tune the patient selection for sTILs-based de-escalation of NAC regimens. At present, there

Published
2021

50. Ovarian Cancer-Specific BRCA-like Copy-Number Aberration Classifiers Detect Mutations Associated with Homologous Recombination Deficiency in the AGO-TR1 Trial

Author

Schouten, Philip C., Richters, Lisa, Vis, Daniel J., Kommoss, Stefan, van Dijk, Ewald, Ernst, Corinna, Kluin, Roelof J. C., Marme, Frederik, Lips, Esther H., Schmidt, Sandra, Scheerman, Esther, Prieske, Katharina, van Deurzen, Carolien H. M., Burges, Alexander, Ewing-Graham, Patricia C., Dietrich, Dimo, Jager, Agnes, de Gregorio, Nikolaus, Hauke, Jan, du Bois, Andreas, Nederlof, Petra M., Wessels, Lodewyk F., Hahnen, Eric, Harter, Philipp, Linn, Sabine C., Schmutzler, Rita K., Schouten, Philip C., Richters, Lisa, Vis, Daniel J., Kommoss, Stefan, van Dijk, Ewald, Ernst, Corinna, Kluin, Roelof J. C., Marme, Frederik, Lips, Esther H., Schmidt, Sandra, Scheerman, Esther, Prieske, Katharina, van Deurzen, Carolien H. M., Burges, Alexander, Ewing-Graham, Patricia C., Dietrich, Dimo, Jager, Agnes, de Gregorio, Nikolaus, Hauke, Jan, du Bois, Andreas, Nederlof, Petra M., Wessels, Lodewyk F., Hahnen, Eric, Harter, Philipp, Linn, Sabine C., and Schmutzler, Rita K.

Abstract

Purpose: Previously, we developed breast cancer BRCA1-like and BRCA2-like copy-number profile shrunken centroid classifiers predictive for mutation status and response to therapy, targeting homologous recombination deficiency (HRD). Therefore, we investigated BRCA1- and BRCA2-like classification in ovarian cancer, aiming to acquire classifiers with similar properties as those in breast cancer. Experimental Design: We analyzed DNA copy-number profiles of germline BRCA1- and BRCA2-mutant ovarian cancers and control tumors and observed that existing breast cancer classifiers did not sufficiently predict mutation status. Hence, we trained new shrunken centroid classifiers on this set and validated them in the independent The Cancer Genome Atlas dataset. Subsequently, we assessed BRCA1/2-like classification and obtained germline and tumor mutation and methylation status of cancer predisposition genes, among them several involved in HR repair, of 300 ovarian cancer samples derived from the consecutive cohort trial AGO-TR1 (NCT02222883). Results: The detection rate of the BRCA1-like classifier for BRCA1 mutations and promoter hypermethylation was 95.6%. The BRCA2-like classifier performed less accurately, likely due to a smaller training set. Furthermore, three quarters of the BRCA1/2-like tumors could be explained by (epi)genetic alterations in BRCA1/2, germline RAD51C mutations and alterations in other genes involved in HR. Around half of the non-BRCA-mutated ovarian cancer cases displayed a BRCA-like phenotype. Conclusions: The newly trained classifiers detected most BRCA-mutated and methylated cancers and all tumors harboring a RAD51C germline mutations. Beyond that, we found an additional substantial proportion of ovarian cancers to be BRCA-like.

Published
2021

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