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

  • Yuko MinamiEmail author
  • Yoshikazu Nishino
  • Masaaki Kawai
  • Hiroshi Tada
  • Seiki Kanemura
  • Minoru Miyashita
  • Takanori Ishida
  • Yoichiro Kakugawa
Original Article



Reproductive factors may influence breast cancer progression and patient survival; however, evidence has been limited.


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.


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, ptrend = 0.03; last birth, HR = 3.10 for ≥ 35 vs. ≤ 29 years, ptrend = 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, ptrend = 0.004).


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.


Breast cancer Survival Age at menarche Parity Reproductive factors Hormone receptor 



We would like to express our appreciation to Dr. Takeshi Okabe and Ms. Misako Takahashi, who cooperated in setting up this study.


This study was supported by Grants-in-Aid from the Japan Society for the Promotion of Science (JSPS) for Scientific Research: (B) (23390169) and (B) (16H05240).

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.


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Copyright information

© The Japanese Breast Cancer Society 2019

Authors and Affiliations

  1. 1.Division of Community HealthTohoku University Graduate School of MedicineSendaiJapan
  2. 2.Division of Cancer Epidemiology and PreventionMiyagi Cancer Center Research InstituteNatoriJapan
  3. 3.Department of Breast SurgeryMiyagi Cancer Center HospitalNatoriJapan
  4. 4.Department of Breast and Endocrine Surgical OncologyTohoku University Graduate School of MedicineSendaiJapan
  5. 5.Center for Preventive MedicineOsaki Citizen HospitalOsakiJapan
  6. 6.Department of Epidemiology and Public HealthKanazawa Medical UniversityKahokuJapan

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