Murphy, Rachel A
Mayo Clinic
School of Population and Public Health, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
Citations 2
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.
Distinct Reproductive Risk Profiles for Intrinsic-Like Breast Cancer Subtypes: Pooled Analysis of Population-Based Studies
Jung, Audrey , Ahearn, Thomas U. , Behrens, Sabine , Middha, Pooja , Bolla, Manjeet K. , Wang, Qin , Arndt, Volker , Aronson, Kristan J. , Brenner, Hermann , Eriksson, Mikael , Evans, D. Gareth , Hadjisavvas, Andreas , Haiman, Christopher A. , Håkansson, Niclas , Hamann, Ute , Hoppe, Reiner , Howell, Anthony , Hunter, David J. , Kosma, Veli‐Matti , Lissowska, Jolanta , Loizidou, Maria A. , Mannermaa, Arto , Maurer, Tabea, Olsson, Håkan , Patel, Alpa V , Perou, Charles M. , Shibli, Rana , Stone, Jennifer , Vachon, Celine M. , Wang, Sophia , Wu, Anna H. , Yang, Xiaohong R. , Zheng, Wei , Easton, Douglas F. , Chatterjee, Nilanjan , García‐Closas, Montserrat , Chang‐Claude, Jenny , Olsson, Håkan , Jung, Audrey Y , Becher, Heiko , Brenner, Hermann , Canzian, Federico , Czene, Kamila , Eliassen, A Heather , Figueroa, Jonine D , Fritschi, Lin , Gabrielson, Marike , Giles, Graham G , Guénel, Pascal , Hadjisavvas, Andreas , Håkansson, Niclas , Hall, Per N , Hüsing, Anika , Koutros, Stella , Kraft, Peter , Marchand, Loïc Le , Lissowska, Jolanta , Loizidou, Maria A , Mannermaa, Arto , Murphy, Rachel A , Olsson, Håkan , Patel, Alpa V , Perou, Charles M , Shu, Xiao-Ou , Southey, Melissa C , Stone, Jennifer , Tamimi, Rulla M , Vachon, Celine M. , Wolk, Alicja , Dunning, Alison M , Pharoah, Paul D P , Easton, Doug , Milne, Roger L , Schmidt, Marjanka K , García-Closas, Montserrat , Chang-Claude, Jenny , Behrens, Sabine , Evans, D Gareth , Arndt, Volker , Kapoor, Pooja Middha , Zheng, Wei , Eriksson, Mikael , Wang, Sophia S , Wang, Qin , Augustinsson, Annelie , Freeman, Laura E. Beane , Becher, Heiko , Canzian, Federico , Carey, Lisa A. , Czene, Kamila , Eliassen, A. Heather , Figueroa, Jonine D. , Fritschi, Lin , Gabrielson, Marike , Giles, Graham G. , Guénel, Pascal , Hopper, John L. , Hüsing, Anika , Kaaks, Rudolf , Koutros, Stella , Kraft, Peter , Lacey, James V. , Marchand, Loı̈c Le , Murphy, Rachel A. , Olshan, Andrew F. , Rennert, Gad , Shu, Xiao‐Ou , Southey, Melissa C. , Tamimi, Rulla M. , Teras, Lauren R. , Troester, Melissa A. , Truong, Thérèse , Wolk, Alicja , Dunning, Alison M. , Pharoah, Paul D.P. , Milne, Roger L. , Schmidt, Marjanka K.
JNCI: Journal of the National Cancer Institute | June 20, 2022 | Volume: 114 | Issue: 12 | Pages: 1706-1719
AbstractBackgroundReproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear.MethodsAnalyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2–like, HER2-enriched–like, and triple-negative breast cancer) and by invasiveness. All statistical tests were 2-sided.ResultsCompared with nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2–like, and HER2-enriched–like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46 for multiparous women with luminal A-like tumors 20 to less than 25 years after last birth and 45 to less than 50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95% CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95% CI = 0.79 to 1.34, for multiparous women 25 to less than 30 years after last birth). Older age at first birth (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) and breastfeeding (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) were associated with lower risk of triple-negative breast cancer but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like.ConclusionsThis large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared with other subtypes, with implications for the understanding of disease etiology and risk prediction.