Tumor subtype-specific associations of hormone-related reproductive factors on breast cancer survival

PLoS One. 2015 Apr 14;10(4):e0123994. doi: 10.1371/journal.pone.0123994. eCollection 2015.

Abstract

Purpose: It 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.

Methods: Among 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.

Results: An 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.

Conclusions: It 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Demography
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Menarche
  • Menopause
  • Middle Aged
  • Proportional Hazards Models
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Risk Factors
  • Survival Rate

Substances

  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptor, ErbB-2

Grants and funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2010-0028631). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.