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BackgroundReproductive 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) and by invasiveness. All statistical tests were 2-sided.ResultsCompared to 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-<25 years after last birth and 45-<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 ConclusionThis large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared to other subtypes, with implications for the understanding of disease etiology and risk prediction.

Original publication

DOI

10.1093/jnci/djac117

Type

Journal article

Journal

Journal of the National Cancer Institute

Publication Date

20/06/2022

Addresses

German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany.

Keywords

CTS Consortium