Citations 4
Clarifying risk-factor associations with quantitative breast tumor features: a pooled analysis of 24 studies
Adams, Daniel , Hurson, Amber N. , Ahearn, Thomas U, Andrulis, Irene L, Antoniou, Antonis C, Auvinen, Päivi, Bane, Anita, González, Amy Berrington de , Bodelon, Clara, Bolla, Manjeet K. , Borrero, Maria , Brenner, Hermann, Brock, Ian W., Camp, Nicola J. , Cessna, Melissa H., Chanock, Stephen J, Chenevix-Trench, G, Copson, ER, Fh, Couch, Devilee, P, Easton, Douglas F, Eccles, Diana, Figueroa, Jonine D, Glendon, Gord, Hamann, U, Hartman, Mikael, Heemskerk-Gerritsen, Bernadette A M, Hodge, James M, Holleczek, Bernd, Hollestelle, A M, Mj, Hooning, Investigators, kConFab, Amor, David, Andrews, Lesley , Antill, Y , Rl, Balleine, Beesley, Jonathan, Bennett, Ian, Bogwitz, Michael, Bodek, Simon, Botes, Leon, Brennan, Meagan, Brown, Melissa, Buckley, Michael, Caldon, Liz, Campbell, Ian, Chakrabarti, Anannya , Chauhan, Deepa, Chauhan, Manisha, Christian, Alice, Cohen, Paul, Colley, Alison, Cui, James, Courtney, Eliza, Cummings, Margaret, Delatycki, Martin, Dickson, Rebecca, Dixon, Joanne, Duijf, Pascal, Edwards, Stacey, Farshid, Gelareh , Fellows, AM, Fenton, Georgina, Field, Michael, Flanagan, James, Fong, Peter, Forrest, Laura, Fox, Stephen, French, Juliet , Friedlander, Michael, Gattas, Mike, George, Peter, Greening, Sian, Harris, Marion, Harraka, Philip, Hayward, Nick, Hoskins, Cass , Hunt, Clare, James, Paul, Jenkins, Mark, Kidd, Alexa, Koehler, Jessica, Kollias, J, Lakhani, Sunil, Lawrence, Mitchell, Lee, Jason , Li, Shuai, Lindeman, Geoff, Lippey, Jocelyn, Lipton, Lara, Loi, Sherene, Mann, Graham, Marsh, Deborah, McLachlan, Sue Anne, Reed, Amy McCart, Milne, Roger, Nightingale, Sophie , O’Connell, Shona, O’Sullivan, Sarah, Reilly, Robert O', Ortega, David Gallego, Pachter, Nick, Pang, Jia-Min, Pathak, Gargi, Patterson, Briony, Phillips, Kelly, Pieper, Ellen, Ramus, Susan, Rickard, Edwina, Ragunathan, Abi, Robinson, Bridget, Skandarajah, Anita, Salisbury, Elizabeth, Saunders, Christobel, Saunus, Jodi, Scott, Rodney, Scott, Clare, Sexton, Adrienne, Shaw, Joanne, Shelling, Andrew, Srinivasa, Shweta , Simpson, Peter, Mc, Southey, Spurdle, Amanda, Taylor, Jessica, Taylor, Renea, Thorne, Heather, Trainer, A H, Tucker, Kathy , Visvader, Jane, Walker, Logan, Williams, Rachael, Winship, I, Young, Mary Ann, Zaheed, Milita , Investigators, S On Behalf Of The Chlovis Study, Tan, Veronique Kiak Mien , Lim, Geok Hoon, Tan, Ern Yu , Tan, Su-Ming, Iau, Philip Tsau Choong , Jakubowska, A, Jones, Michael E. , Jones, Louise , Jones, Brandt, Jung, Audrey, Kaaks, Rudolf, Keeman, Renske , Lawrence, Scott, Li, J M, Lubiński, J, Mannermaa, Arto, Manoochehri, Mehdi, Martens, John W M, Mesker, Wilma E, Muhammad, Noor , Obi, Nadia, Olson, Janet E, Patel, Alpa V, Prajzendanc, Karolina , Ruddy, Kathryn J, Safizadeh, Fatemeh , Schöttker, Ben, Tengström, Maria , Le, Teras, Timmermans, M, Tollenaar, RA, Vachon, Celine M, Wang, Q, Yang, Xiaohong R, Zamora, M Pilar, Chang-Claude, Jenny, Schmidt, M K, Pharoah, Paul D P, Abubakar, Mustapha, Eccles, Diana , Ahearn, Thomas U. , Eccles, Diana , Jones, Michael E , Jones, J. Louise , Berrington de Gonzalez, Amy , Antoniou, Antonis C. , Bane, Anita, Behrens, Sabine , Białkowska, Katarzyna , Bodelón, Clara , Brenner, Hermann , Broeks, Annegien , Chanock, Stephen Jacob , Chenevix‐Trench, Georgia , Copson, Ellen , Couch, Fergus J, Cox, Angela , Cross, Simon S. , Devilee, Peter , Dunning, Alison M. , Easton, Douglas F. , Figueroa, Jonine D. , Glendon, Gord, González‐Neira, Anna , Hartikainen, Jaana M. , Hartman, Mikael , Heemskerk‐Gerritsen, Bernadette A. M. , Ho, Peh Joo , Hodge, James M. , Holleczek, Bernd , Hollestelle, Antoinette , Hooning, Maartje J. , Investigators, kConFab, Balleine, Rosemary L. , Bennett, Ian, Bogwitz, Michael R. , Bodek, Simon , Botes, Leon P., Buckley, Michael , Cohen, Paul A. , Crook, Ashley , Courtney, Eliza , Dawson, Sarah‐Jane , DeFazio, Anna , Delatycki, Martin B. , Duijf, Pascal H. G. , Fellows, Andrew, Fenton, Georgina L. , Flanagan, James M. , Forrest, Laura Elenor , Friedländer, Michael , Harraka, Philip A. , Kidd, Alexa, Kollias, James, Lakhani, Sunil R. , Lawrence, Mitchell, Lindeman, Geoffrey J. , Lippey, Jocelyn , Loi, Sherene , Reed, Amy E. McCart , Milne, Roger L , Gallego‐Ortega, David , Pathak, Gargi, Pearn, Amy , Robinson, Bridget A. , Skandarajah, Anita Rohini , Salisbury, Elizabeth, Saunders, Christobel , Saunus, Jodi M. , Savas, Peter Stephen , Sexton, Adrienne , Shelling, Andrew Neil , Simpson, Peter, Spurdle, Amanda B. , Visvader, Jane E. , Williams, Rachael, Tan, Bien‐Keem , Lim, Geok Hoon , Kaaks, Rudolf , Lawrence, Scott M. , Lissowska, Jolanta , Mannermaa, Arto , Manoochehri, Mehdi, Mesker, Wilma E. , Mulligan, Anna Marie , Obi, Nadia , Olson, Janet E. , Osório, Ana , Ottewell, Penelope Dawn , Patel, Alpa V , Pita, Guillermo , Rashid, Muhammad Usman , Ruddy, Kathryn J. , Schöttker, Ben , Seibold, Petra , Tapper, William , Teras, Lauren R , Timmermans, Mieke, Vachon, Celine M. , Wesseling, Jelle , Yadav, Siddhartha , Chang‐Claude, Jenny , Schmidt, Marjanka K. , Abubakar, Mustapha , García‐Closas, Montserrat
JNCI: Journal of the National Cancer Institute | July 18, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Background Breast cancer is etiologically heterogeneous, but which risk factors differ in their associations across tumor subtypes remains unclear. We conducted a large, pooled analysis to evaluate independent, dose-response associations between breast cancer risk factors and quantitative tumor features. Methods Analyses of 15,731 invasive breast cancers from 24 studies evaluated associations (p-trend) between reproductive and hormonal factors, body mass index (BMI), alcohol, smoking, and family history in relation to quantitative immunohistochemistry measures on tissue microarrays (ER, PR, HER2, KI67, TP53) and tumor grade. Analyses in a subset of 10 population-based studies estimated subtype-specific odds ratios (ORs) comparing cases to controls. A Bayesian False Discovery Probability (BFDP) <0.2 was used to identify associations with strong statistical evidence. Results Nulliparity and later age at menopause were associated with higher ER-positivity (p-trend=0.021 and 0.001, respectively), with corresponding OR[ER+] (95% CI) = 1.49 (1.16-1.90) for nulliparous vs. parous and 1.07 (1.03-1.11) per 5 years. Current combined menopausal hormone therapy (MHT) use was associated with lower grade (p-trend<0.001), with OR [grade1] = 3.37 (2.69-4.21) for current vs. never users. Higher BMI was associated with lower ER-positivity and higher grade in premenopausal women (p-trend<0.001 and <0.001), with OR[ER+] = 0.80 (0.74-0.87) and OR[grade1] = 0.75 (0.63-0.88) per 5 units, and with higher PR-positivity and higher grade in postmenopausal women (p-trend<0.001 and <0.001), with OR[PR+] = 1.08 (1.03-1.14) and OR[grade 3] = 1.10 (1.04-1.17) per 5 units. Conclusion This pooled analysis of 15,731 cases showed that nulliparity, age at menopause, MHT, and BMI have independent, dose-response associations with ER, PR, and grade, clarifying patterns of etiologic heterogeneity. Associations with HER2, KI67 and TP53, or other risk factors did not meet our threshold for strong evidence.
Threshold-Based Overlap of Breast Cancer High-Risk Classification Using Family History, Polygenic Risk Scores, and Traditional Risk Models in 180,398 Women
Ho, Peh Joo , Loo, Christine Kim Yan , Lim, Ryan Jak Yang, Goh, Mui Heng, Abubakar, Mustapha , Ahearn, Thomas U. , Andrulis, Irene L. , Antonenkova, Natalia, Aronson, Kristan J. , Augustinsson, Annelie , Behrens, Sabine , Bodelón, Clara , Bogdanova, Natalia , Bolla, Manjeet K. , Brantley, Kristen D. , Brenner, Hermann , Byers, Helen L., Camp, Nicola J. , Cessna, Melissa H., Chang-Claude, Jenny, Choi, Ji-Yeob , Czene, Kamila , Dörk, Thilo , Eliassen, A. Heather , Engel, Christoph , Eriksson, Mikael , Evans, D. Gareth , Fritschi, Lin , Genkinger, Jeanine M. , Geurts-Giele, Willemina R.R. , Glendon, Gord, Hall, Per , Hamann, U. , Ho, Cecilia Y.S., Hooning, Maartje J. , Hoppe, Reiner , Humphreys, Keith , Ito, Hidemi , Jakubowska, Anna , Jernström, Helena , John, Esther M. , Johnson, Nichola , Kang, Daehee , Kim, Sung‐Won , Kitahara, Cari M. , Ko, Yon-Dschun, Kraft, Peter, Kwong, Ava , Lambrechts, Diether, Larsson, Susanna C. , Li, Shuai , Lindblom, Annika , Linet, Martha, Lissowska, Jolanta , Lophatananon, Artitaya , MacInnis, Robert J. , Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Matsuo, Keitaro , Michailidou, Kyriaki , Taib, Nur Aishah Mohd , Murphy, Rachel A. , Newman, William G. , Obi, Nadia , Olopade, Olufunmilayo I., Panayiotidis, Mihalis I. , Park, Sue K. , Park‐Simon, Tjoung‐Won , Patel, Alpa V , Peterlongo, Paolo , Plaseska‐Karanfilska, Dijana , Pylkäs, Katri , Rashid, Muhammad Usman , Rodríguez, Juan , Sandler, Dale P. , Sawyer, Elinor J. , Scott, Christopher G. , Shahi, Shamim , Shu, Xiao‐Ou , Shulman, Katerina, Simard, Jacques , Southey, Melissa C., Stone, Jennifer , Taylor, Jack A. , Teo, Soo‐Hwang , Teras, Lauren R. , Vachon, Celine M., Houdt, Maxime Van , Verhoeven, Jelle , Weinberg, Clarice R. , Wolk, Alicja , Yamaji, Taiki , Yip, Cheng Har , Zheng, Wei , Hartman, Mikael , Li, Jingmei , Investigators, on behalf of the ABCTB, Investigators, kConFab, Investigators, MyBrCa, Investigators, SGBCC, Olopade, Olufunmilayo I. , Lambrechts, Diether , Lambrechts, Diether , Hamann, Ute , Hooning, Maartje J. , Bogdanova, Natalia V , Czene, Kamila , Dörk, Thilo , Eliassen, A Heather , Engel, Christoph , Eriksson, Mikael , Evans, D Gareth , Fletcher, Olivia , Fritschi, Lin , Genkinger, Jeanine , Hall, Per N , Ho, Cecilia Y S , Humphreys, Keith , Ito, Hidemi , Jakubowska, Anna , Jernström, Helena , Johnson, Nichola , Kim, Sung-Won , Kitahara, Cari M , Kwong, Ava , Larsson, Susanna C , Li, Shuai , Lindblom, Annika , Lissowska, Jolanta , Lophatananon, Artitaya , Maclnnis, Robert , Matsuo, Keitaro , Michailidou, Kyriaki , Mohd Taib, Nur Aishah , Murphy, Rachel A , Newman, William G , Obi, Nadia , Panayiotidis, Mihalis I , Park, Sue K , Park-Simon, Tjoung-Won , Peterlongo, Paolo , Plaseska-Karanfilska, Dijana , Pylkäs, Katri , Rashid, Muhammad U , Rennert, Gad , Rodriguez, Juan , Sandler, Dale P , Sawyer, Elinor J , Scott, Christopher , Shu, Xiao-Ou , Simard, Jacques , Stone, Jennifer , Taylor, Jack A , Teo, Soo H , Teras, Lauren R , Houdt, Maxime Van , Verhoeven, Jelle , Weinberg, Clarice R , Wolk, Alicja , Zheng, Wei , Hartman, Mikael , Li, Jingmei , Lambrechts, Diether , Behrens, Sabine , John, Esther M , Olopade, Olufunmilayo I , Lambrechts, Diether , Augustinsson, Annelie , Brenner, Hermann , Camp, Nicola J , Brantley, Kristen D , Lim, Ryan Jak Yang, Byers, Helen, Castelao, Jose E. , Chang‐Claude, Jenny , Chanock, Stephen Jacob , Chenevix‐Trench, Georgia , Colonna, Sarah V. , Daly, Mary Beryl , Derouane, Françoise , Fletcher, Olivia , Gago-Domínguez, Manuela , Ho, Weang-Kee , Howell, Anthony , Iwasaki, Motoki , Ko, Yon‐Dschun, Mannermaa, Arto , Manoukian, Siranoush , Margolin, Sara , Milne, Roger L. , Muir, Kenneth , O’Brien, Katie M. , Rennert, Gad , Saloustros, Emmanouil , Southey, Melissa C. , Terry, Mary Beth , Torres, Diana , Investigators, on behalf of the ABCTB, Investigators, kConFab, Investigators, MyBrCa, Investigators, SGBCC
Cancers | November 3, 2025 | Volume: 17 | Issue: 21 | Pages: 3561
Background: Breast cancer polygenic risk scores (PRS) and traditional risk models (e.g., the Gail model [Gail]) are known to contribute largely independent information, but it is unclear how the overlap varies by ancestry, age, disease type (invasive breast cancer, DCIS), and risk threshold. Methods: In a retrospective case–control study, we evaluated risk prediction performance in 180,398 women (161,849 of European ancestry; 18,549 of Asian ancestry). Odds ratios (ORs) from logistic regression models and the area under the receiver operating characteristic curve (AUC) were estimated. Results: PRS for invasive disease showed a stronger association in younger (<50 years) women (OR = 2.51, AUC = 0.622) than in women ≥ 50 years (OR = 2.06, AUC = 0.653) of European ancestry. PRS performance in Asians was lower (OR range = 1.62–1.64, AUC = 0.551–0.600). Gail performance was modest across groups and poor in younger Asian women (OR = 0.94–0.99, AUC = 0.523–0.533). Age interactions were observed for both PRS (p < 0.001) and Gail (p < 0.001) in Europeans, whereas in Asians, age interaction was observed only for Gail (invasive: p < 0.001; DCIS: p = 0.002). PRS identified more high-risk individuals than Gail in Asian populations, especially ≥50 years, while Gail identified more in Europeans. Overlap between PRS, Gail, and family history was limited at higher thresholds. Calibration analysis, comparing empirical and model-based ROC curves, showed divergence for both PRS and Gail (p < 0.001), which indicates miscalibration. In Europeans, family history and prior biopsies drove Gail discrimination. In younger Asians, age at first live birth was influential. Conclusions: PRS adds value to risk stratification beyond traditional tools, especially in younger women and Asian ancestry populations.
Association of the CHEK2 c. 1100delC variant, radiotherapy, and systemic treatment with contralateral b
Morra, Anna , Schreurs, Maartje A. C. , Andrulis, Irene L. , Anton‐Culver, Hoda , Beckmann, Matthias W. , Bolla, Manjeet K. , Camp, Nicola J. , Cessna, Melissa H., Chang‐Claude, Jenny , Collaborators, NBCS, Dörk, Thilo , Easton, Douglas F. , Eccles, Diana M., Evans, D. Gareth , Fasching, Peter A. , Flyger, Henrik, García‐Closas, Montserrat , Graßmann, Felix , Gündert, Melanie , Hahnen, Eric , Haiman, Christopher A. , Hamann, Ute, Harrington, Patricia, Hoppe, Reiner , Hopper, John L. , Houlston, Richard S. , Howell, Anthony, Investigators, ABCTB, Investigators, kConFab, Janni, Wolfgang, John, Esther M. , Johnson, Nichola , Jones, Michael E. , Kristensen, Vessela N. , Kurian, Allison W. , Lambrechts, Diether , Lindblom, Annika , Mannermaa, Arto, Mavroudis, Dimitrios, Muranen, Taru , Nevelsteen, Ines, Neven, Patrick , Newman, William G. , Obi, Nadia , Offit, Kenneth , Park‐Simon, Tjoung‐Won , Patel, Alpa V. , Peterlongo, Paolo , Phillips, Kelly‐Anne , Plaseska‐Karanfilska, Dijana , Rack, Brigitte , Rhenius, Valerie , Romero, Atocha , Sawyer, Elinor J. , Schmutzler, Rita K. , Schuetze, Sabine, Shah, Mitul , Smichkoska, Snezhana , Tollenaar, Rob A.�E.�M. , Tomlinson, Ian , Vachon, Celine M. , Veen, Elke M. van , Wang, Qin , Wendt, Camilla, Wildiers, Hans , Pharoah, Paul D.P. , Adank, Muriel A. , Hooning, Maartje J. , Howell, Anthony , Ramus, Susan J. , Bojesen, Stig E. , Eccles, Diana , Cummings, Margaret C. , Loi, Sherene , Lambrechts, Diether , Howell, Sacha J. , Bojesen, Stig E , Dörk, Thilo , Figueroa, Jonine D , Gabrielson, Marike , Gago-Dominguez, Manuela , García-Sáenz, José A , Hahnen, Eric , Hartikainen, Jaana M , Jernström, Helena , John, Esther M , Lambrechts, Diether , Muranen, Taru A , Nevanlinna, H , Patel, Alpa V , Pylkäs, Katri , Rashid, Muhammad U , Hooning, Maartje J. , Lambrechts, Diether , Peterlongo, Paolo , Ramus, Susan J , Pharoah, Paul D P , Eccles, Diana , Houlston, Richard S , Anton-Culver, Hoda , Evans, D Gareth , Jones, Michael E , Newman, William G , Romero, Atocha , García-Closas, Montserrat , Kurian, Allison W , Loi, Sherene , Bojesen, Stig E , Phillips, Kelly-Anne , Wildiers, Hans , Lindblom, Annika , Plaseska-Karanfilska, Dijana , Sawyer, Elinor J , Augustinsson, Annelie , Behrens, Sabine , Brauch, Hiltrud , Broeks, Annegien , Buys, Saundra S. , Castelao, Jose E. , Chung, Wendy K. , Collaborators, NBCS, Colonna, Sarah V. , Couch, Fergus J. , Cox, Angela , Cross, Simon S. , Czene, Kamila , Daly, Mary Beryl , Dennis, Joe , Devilee, Peter , Dunning, Alison M. , Dwek, Miriam , Eriksson, Mikael , Fehm, Tanja , Figueroa, Jonine D. , Gabrielson, Marike , Gago-Domínguez, Manuela , García-Sáenz, José Á. , Genkinger, Jeanine M. , Hartikainen, Jaana M. , Howell, Anthony, Investigators, ABCTB, Investigators, kConFab, Jakubowska, Anna , Jernström, Helena , Marchand, Loı̈c Le , Lubiński, Jan , Lux, Michael P. , Mannermaa, Arto, Mulligan, Anna Marie , Nevanlinna, Heli , Olshan, Andrew F. , Polley, Eric C. , Presneau, Nadège , Pylkäs, Katri , Radice, Paolo , Rashid, Muhammad Usman , Robson, Mark E. , Saloustros, Emmanouil , Scott, Christopher G. , Southey, Melissa C. , Tapper, William , Teras, Lauren R. , Tomczyk, Katarzyna , Troester, Melissa A. , Vachon, Celine M. , Winqvist, Robert , Ziogas, Argyrios , Hall, Per N , Hollestelle, Antoinette , Schmidt, Marjanka K.
Cancer Medicine | July 4, 2023 | Volume: 12 | Issue: 15 | Pages: 16142-16162
Abstract Background Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC‐specific survival (BCSS) compared to non‐carriers. Aim To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Methods Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow‐up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi‐state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi‐state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non‐carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09–1.56)]. Conclusion Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.
Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival
Morra, Anna , Andrulis, Irene L. , Beckmann, Matthias W. , Bolla, Manjeet K. , Camp, Nicola J. , Cessna, Melissa H., Chang‐Claude, Jenny , Collaborators, NBCS, Daly, Mary B., Easton, Douglas F. , Eccles, Diana M., Evans, D. Gareth , Fasching, Peter A. , Flyger, Henrik, García‐Closas, Montserrat , Gündert, Melanie , Hahnen, Eric , Haiman, Christopher A. , Hamann, Ute, Harrington, Patricia, Hoppe, Reiner , Howell, Anthony , Investigators, ABCTB, Investigators, kConFab, Janni, Wolfgang, Johnson, Nichola , Kristensen, Vessela N. , Lindblom, Annika , Mannermaa, Arto , Mavroudis, Dimitrios, Nevelsteen, Ines, Neven, Patrick , Obi, Nadia , Offit, Kenneth , Park‐Simon, Tjoung‐Won , Patel, Alpa V. , Phillips, Kelly‐Anne , Plaseska-Karanfilska, Dijana, Rack, Brigitte , Rhenius, Valerie , Sawyer, Elinor J. , Schmutzler, Rita K. , Schuetze, Sabine, Shah, Mitul , Smichkoska, Snezhana , Tollenaar, Rob A.�E.�M. , Tomlinson, Ian , Vachon, Celine M. , Veen, Elke M. van , Wang, Qin , Wendt, Camilla, Wildiers, Hans , Adank, Muriel A. , Hooning, Maartje J. , Eccles, Diana , Plaseska‐Karanfilska, Dijana , Eccles, Diana , Evans, D Gareth , García-Closas, Montserrat , Phillips, Kelly-Anne , Wildiers, Hans , Lindblom, Annika , Plaseska-Karanfilska, Dijana , Sawyer, Elinor J , Schreurs, Maartje A. C. , Anton‐Culver, Hoda , Augustinsson, Annelie , Behrens, Sabine , Bojesen, Stig E. , Brauch, Hiltrud , Broeks, Annegien , Buys, Saundra S. , Castelao, Jose E. , Chung, Wendy K. , Colonna, Sarah V. , Couch, Fergus J. , Cox, Angela , Cross, Simon S. , Czene, Kamila , Dennis, Joe , Devilee, Peter , Dörk, Thilo , Dunning, Alison M. , Dwek, Miriam , Eriksson, Mikael , Fehm, Tanja , Figueroa, Jonine D. , Gabrielson, Marike , Gago-Domínguez, Manuela , García-Sáenz, José Á. , Genkinger, Jeanine M. , Graßmann, Felix , Hartikainen, Jaana M. , Hopper, John L. , Houlston, Richard S. , Jakubowska, Anna , Jernström, Helena , John, Esther M. , Jones, Michael E. , Kurian, Allison W. , Lambrechts, Diether , Marchand, Loı̈c Le , Lubiński, Jan , Lux, Michael P. , Mulligan, Anna Marie , Muranen, Taru , Nevanlinna, Heli , Newman, William G. , Olshan, Andrew F. , Peterlongo, Paolo , Polley, Eric C. , Presneau, Nadège , Pylkäs, Katri , Radice, Paolo , Rashid, Muhammad Usman , Robson, Mark E. , Romero, Atocha , Saloustros, Emmanouil , Scott, Christopher, Southey, Melissa C. , Tapper, William , Teras, Lauren R. , Tomczyk, Katarzyna , Troester, Melissa A. , Vachon, Celine M. , Winqvist, Robert , Ziogas, Argyrios , Hall, Per N , Pharoah, Paul D.P. , Hollestelle, Antoinette , Schmidt, Marjanka K.
No container title available | February 13, 2023 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. We aimed to assess the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Analyses were based on 82,701 women diagnosed with invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations of treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR(95%CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR(95%CI) :1.30 (1.09–1.56)]. In conclusion, systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk. (Main MS: 3201 words)