Distinct Reproductive Risk Profiles for Intrinsic-Like Breast Cancer Subtypes: Pooled Analysis of Population-Based Studies. (20th June 2022)

• Record Type: Journal Article
• Authors: Jung, Audrey Y; Ahearn, Thomas U; Behrens, Sabine; Middha, Pooja; Bolla, Manjeet K; Wang, Qin; Arndt, Volker; Aronson, Kristan J; Augustinsson, Annelie; Beane Freeman, Laura E; Becher, Heiko; Brenner, Hermann; Canzian, Federico; Carey, Lisa A; Czene, Kamila; Eliassen, A Heather; Eriksson, Mikael; Evans, D Gareth; Figueroa, Jonine D; Fritschi, Lin; Gabrielson, Marike; Giles, Graham G; Guénel, Pascal; Hadjisavvas, Andreas; Haiman, Christopher A; Håkansson, Niclas; Hall, Per; Hamann, Ute; Hoppe, Reiner; Hopper, John L; Howell, Anthony; Hunter, David J; Hüsing, Anika; Kaaks, Rudolf; Kosma, Veli-Matti; Koutros, Stella; Kraft, Peter; Lacey, James V; Le Marchand, Loic; Lissowska, Jolanta; Loizidou, Maria A; Mannermaa, Arto; Maurer, Tabea; Murphy, Rachel A; Olshan, Andrew F; Olsson, Håkan; Patel, Alpa V; Perou, Charles M; Rennert, Gad; Shibli, Rana; Shu, Xiao-Ou; Southey, Melissa C; Stone, Jennifer; Tamimi, Rulla M; Teras, Lauren R; Troester, Melissa A; Truong, Thérèse; Vachon, Celine M; Wang, Sophia S; Wolk, Alicja; Wu, Anna H; Yang, Xiaohong R; Zheng, Wei; Dunning, Alison M; Pharoah, Paul D P; Easton, Douglas F; Milne, Roger L; Chatterjee, Nilanjan; Schmidt, Marjanka K; García-Closas, Montserrat; Chang-Claude, Jenny;
• Is Part Of: Journal of the National Cancer Institute. Volume 114:Number 12(2022)
• Page Start: 1706
• Page End: 1719
• Publication Date: 2022-06-20
• Subjects: Cancer -- Periodicals; Cancer -- Research -- Periodicals; 616.994
• DOI: 10.1093/jnci/djac117
• Languages: English
• ISSNs: 0027-8874

Abstract

Abstract: Background: Reproductive 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. Methods: Analyses 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. Results: Compared 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 ( P heterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) and breastfeeding ( P heterogeneity < .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. Conclusions: This 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.