title: Tumor subtype-specific associations of hormone-related reproductive factors on breast cancer survival.
abstract: OBJECTIVE
  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.
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors: Nan
authors: N
authors: Song
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Ji-Yeob
authors: JY
authors: Choi
authors: Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea; Division of Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, United States of America.
authors: Hyuna
authors: H
authors: Sung
authors: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Sujee
authors: S
authors: Jeon
authors: Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.
authors: Seokang
authors: S
authors: Chung
authors: Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Minkyo
authors: M
authors: Song
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Sue K
authors: SK
authors: Park
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors: Wonshik
authors: W
authors: Han
authors: Department of Surgery, University of Ulsan College of Medicine and ASAN Medical Center, Seoul, Korea.
authors: Jong Won
authors: JW
authors: Lee
authors: Division of Cancer Epidemiology and Management, National Cancer Center, Goyang-si, Gyeonggi-do, Korea.
authors: Mi Kyung
authors: MK
authors: Kim
authors: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Keun-Young
authors: KY
authors: Yoo
authors: Department of Surgery, University of Ulsan College of Medicine and ASAN Medical Center, Seoul, Korea.
authors: Sei-Hyun
authors: SH
authors: Ahn
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors: Dong-Young
authors: DY
authors: Noh
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Daehee
authors: D
authors: Kang
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D003710:Demography; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008572:Menarche; D008593:Menopause; D008875:Middle Aged; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone