Abstract
PurposeIt is inconclusive whether reproductive factors, which are known as risk factors of breast cancer, also influence survival. We investigated overall and subtype-specific associations between reproductive factors and breast cancer survival.MethodsAmong 3,430 incident breast cancer patients who enrolled in the Seoul Breast Cancer Study, 269 patients (7.8%) died and 528 patients (15.4%) recurred. The overall and subtype-specific associations of reproductive factors including age at menarche and menopause, duration of estrogen exposure, menstrual cycle, parity, age at first full-term pregnancy, number of children, age at last birth, time since the last birth, and duration of breastfeeding, on overall and disease-free survival (OS and DFS) were estimated by hazard ratios (HRs) and 95% confidence intervals (95% CIs) using a multivariate Cox proportional hazard model.ResultsAn older age at menarche (HR for OS=1.10, 95% CI=1.03-1.19), a greater number of children (≥4 vs. 2, HR for DFS=1.58, 95% CI=1.11-2.26), and a shorter time since last birth (<5 vs. ≥20 years, HR for DFS=1.67, 95% CI=1.07-2.62) were associated with worse survival while longer duration of estrogen exposure with better survival (HR for DFS=0.97, 95% CI=0.96-0.99). In the stratified analyses by subtypes, those associations were more pronounced among women with hormone receptor and human epidermal growth factor 2 positive (HR+ HER2+) tumors.ConclusionsIt is suggested that reproductive factors, specifically age at menarche, number of children, time since last birth, and duration of estrogen exposure, could influence breast tumor progression, especially in the HR+ HER2+ subtype.
Highlights
Reproductive factors associated with prolonged exposure of endogenous estrogen exposure affect the pathogenesis of breast cancer[1]
An older age at menarche (HR for overall survival (OS)=1.10, 95% confidence intervals (95% confidence intervals (CIs))=1.03-1.19), a greater number of children (4 vs. 2, hazard ratios (HRs) for disease-free survival (DFS)=1.58, 95% CI=1.11-2.26), and a shorter time since last birth (
In the stratified analyses by subtypes, those associations were more pronounced among women with hormone receptor and human epidermal growth factor 2 positive (HR+ human epidermal growth factor receptor 2 (HER2)+) tumors
Summary
Reproductive factors associated with prolonged exposure of endogenous estrogen exposure affect the pathogenesis of breast cancer[1]. Their effects on overall breast cancer survival have been inconsistent in previous studies on age at menarche[2,3], age at first full-term pregnancy (FFTP)[4,5,6,7,8], status[5,9,10,11,12,13,14] or number[5,7,10,15,16,17,18,19] of parity, and number of years since last birth[5,7,13,14,15,18,19,20,21,22,23,24,25,26,27]. The aim of this study was to investigate associations between reproductive factors and breast cancer survival according to diverse clinicopathological subgroups including intrinsic tumor subtypes Reproductive factors are associated with intrinsic tumor subtypes[29] and with diverse clinicopathological characteristics which include tumor stage, grade, histologic subtype and estrogen and progesterone receptor (ER and PR) status, and the differences in the associations with breast cancer survival could be due to these reproductive factors [30,31].
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