Distinct Reproductive Risk Profiles for Intrinsic-Like Breast Cancer Subtypes: Pooled Analysis of Population-Based Studies
Creators: name: Olshan, A.F.
name: Jung, A.Y
name: Milne, R.L.
name: Easton, D.F.
name: Kosma, V.-M.
name: Dunning, A.M.
name: Hunter, D.J.
name: Fritschi, L
name: Hadjisavvas, A
name: Lissowska, J.
name: Lacey, J.V.
name: Kraft, P.
name: Carey, L.A
name: Hakansson, N
name: Maurer, T.
name: Hoppe, R.
name: Eliassen, A.H
name: Wang, S.S.
name: Mannermaa, A.
name: Eriksson, M
name: Vachon, C.M.
name: Pharoah, P.D.P.
name: Kaaks, R.
name: Aronson, K.J
name: Guenel, P
name: Augustinsson, A
name: Ahearn, T.U
name: Stone, J.
name: Gabrielson, M
name: Le Marchand, L.
name: Brenner, H
name: Czene, K
name: Canzian, F
name: Yang, X.R.
name: Wu, A.H.
name: Wang, Q
name: Wolk, A.
name: Figueroa, J.D
name: Evans, D.G
name: Koutros, S.
name: Hüsing, A.
name: Olsson, H.
name: Arndt, V
name: Behrens, S
name: Troester, M.A.
name: Chang-Claude, J.
name: Chatterjee, N.
name: Howell, A.
name: Rennert, G.
name: Perou, C.M.
name: Middha, P
name: Bolla, M.K
name: Southey, M.C.
name: Garcia-Closas, M.
name: Teras, L.R.
name: Tamimi, R.M.
name: Loizidou, M.A.
name: Beane Freeman, L.E
name: Becher, H
name: Patel, A.V.
name: Giles, G.G
name: Truong, T.
name: Schmidt, M.K.
name: Hamann, U.
name: Hall, P.
name: Haiman, C.A
name: Hopper, J.L.
name: Murphy, R.A.
name: Zheng, W.
name: Shibli, R.
name: Shu, X.-O.
Publisher: name: Oxford University Press
Year: 2022

description: 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 23353 cases and 71072 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 (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. 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.