PMID- 25875532 OWN - NLM STAT- MEDLINE DCOM- 20160419 LR - 20220331 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 4 DP - 2015 TI - Tumor subtype-specific associations of hormone-related reproductive factors on breast cancer survival. PG - e0123994 LID - 10.1371/journal.pone.0123994 [doi] LID - e0123994 AB - 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. FAU - Song, Nan AU - Song N AD - Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. FAU - Choi, Ji-Yeob AU - Choi JY AD - 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. FAU - Sung, Hyuna AU - Sung H AD - 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. FAU - Jeon, Sujee AU - Jeon S AD - Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea. FAU - Chung, Seokang AU - Chung S AD - Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea. FAU - Song, Minkyo AU - Song M AD - Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea. FAU - Park, Sue K AU - Park SK AD - 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. FAU - Han, Wonshik AU - Han W AD - Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Surgery, Seoul National University College of Medicine, Seoul, Korea. FAU - Lee, Jong Won AU - Lee JW AD - Department of Surgery, University of Ulsan College of Medicine and ASAN Medical Center, Seoul, Korea. FAU - Kim, Mi Kyung AU - Kim MK AD - Division of Cancer Epidemiology and Management, National Cancer Center, Goyang-si, Gyeonggi-do, Korea. FAU - Yoo, Keun-Young AU - Yoo KY AD - Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea. FAU - Ahn, Sei-Hyun AU - Ahn SH AD - Department of Surgery, University of Ulsan College of Medicine and ASAN Medical Center, Seoul, Korea. FAU - Noh, Dong-Young AU - Noh DY AD - Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Surgery, Seoul National University College of Medicine, Seoul, Korea. FAU - Kang, Daehee AU - Kang D AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150414 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Receptors, Estrogen) RN - 0 (Receptors, Progesterone) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adult MH - Aged MH - Breast Neoplasms/metabolism/mortality/*pathology MH - Demography MH - Disease-Free Survival MH - Female MH - Follow-Up Studies MH - Humans MH - Menarche MH - Menopause MH - Middle Aged MH - Proportional Hazards Models MH - Receptor, ErbB-2/metabolism MH - Receptors, Estrogen/metabolism MH - Receptors, Progesterone/metabolism MH - Risk Factors MH - Survival Rate PMC - PMC4397050 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2015/04/16 06:00 MHDA- 2016/04/20 06:00 PMCR- 2015/04/14 CRDT- 2015/04/16 06:00 PHST- 2014/09/15 00:00 [received] PHST- 2015/02/25 00:00 [accepted] PHST- 2015/04/16 06:00 [entrez] PHST- 2015/04/16 06:00 [pubmed] PHST- 2016/04/20 06:00 [medline] PHST- 2015/04/14 00:00 [pmc-release] AID - PONE-D-14-41436 [pii] AID - 10.1371/journal.pone.0123994 [doi] PST - epublish SO - PLoS One. 2015 Apr 14;10(4):e0123994. doi: 10.1371/journal.pone.0123994. eCollection 2015.