Reproductive history and breast cancer survival: a prospective patient cohort study in Japan

Background: Reproductive factors may influence breast cancer progression and patient survival; however, evidence has been limited. Methods: The associations of reproductive factors with tumor characteristics and patient survival were analyzed among 1468 breast cancer patients diagnosed during 1997–2013 at a single institute in Japan. The patients were followed until 2016. During a median follow-up period of 8.6 years, 272 all-cause and 199 breast cancer deaths were documented. Results: In case–case comparisons, later age at menarche was inversely associated with advanced tumors. Nulliparous patients tended to have receptor-positive [estrogen receptor (ER)+ or progesterone receptor (PR)+] tumors. Conversely, the Cox proportional-hazards model including adjustment for tumor characteristics revealed U-shaped relationship between parity number and the risk of all-cause death among the patients overall [hazard ratio (HR) = 2.10 for nulliparous, 1.28 for 2, and 1.50 for ≥ 3 vs. one child]. According to hormone receptor, later age at menarche and later age at last birth were positively associated with the risk of all-cause death among patients with ER– and PR– cancer (menarche, HR = 2.18 for ≥ 15 vs. ≤ 12 years, p_trend = 0.03; last birth, HR = 3.10 for ≥ 35 vs. ≤ 29 years, p_trend = 0.01). A shorter time since last birth was associated with the risk of death among receptor-positive patients (HR = 5.72 for ≤ 4 vs. ≥ 10 years, p_trend = 0.004). Conclusion: The results indicate that the timing of menarche and parity have significant effects on patient survival, providing clues for understanding the association between women’s life course and breast cancer outcome.