Breast Cancer Research and Treatment

, Volume 144, Issue 1, pp 1–10 | Cite as

Reproductive risk factors and breast cancer subtypes: a review of the literature

  • Kristin N. Anderson
  • Richard B. Schwab
  • Maria Elena Martinez


Aside from age, sex, and family history, risk of developing breast cancer is largely linked to reproductive factors, which characterize exposure to sex hormones. Given that, molecular testing at the tumor level is currently possible, clinical characterization of tumor subtypes is routinely conducted to guide treatment decisions. However, despite the vast amount of published data from observational studies on reproductive factor associations and breast cancer risk, relatively fewer reports have been published on associations specific to breast tumor subtypes. We conducted a review of the literature and summarized the results of associations between reproductive factors and risk or odds of three distinct tumor subtypes: estrogen receptor/progesterone receptor positive (hormone receptor positive, HR+ tumors), tumors overexpressing the human epidermal receptor 2 protein (HER2+), and triple negative breast cancer (TNBC), which lacks the three markers. Results show that the most consistent evidence for associations with reproductive risk factors exists for HR+ breast cancers, with nulliparity, current use of menopausal hormone therapy, and prolonged interval between menarche and age at first birth being the strongest risk factors; increased age at first birth and decreased age at menarche were fairly consistently associated with HR+ cancers; and though less consistent, older age at menopause was also positively associated, while lactation was inversely associated with HR+ tumors. Fewer consistent associations have been reported for TNBC. The single protective factor most consistently associated with TNBC was longer duration of breastfeeding. Increased parity, younger age at first birth, older age at menarche, and oral contraceptive use were less consistently shown to be associated with TNBC. No remarkable associations for HER2+ breast cancers were evident, although this was based on relatively scarce data. Findings suggest heterogeneity in reproductive risk factors for the distinct subtypes of breast tumors, which may have implications for recommended prevention strategies.


Breast tumor subtype Reproductive factors Triple negative breast cancer Tumor heterogeneity 



The authors thank Malaika Tobias for her contribution in the preparation of the manuscript. Grant support for this manuscript includes NIH/NCI grant UO1CA153086.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10549_2014_2852_MOESM1_ESM.docx (129 kb)
Supplementary material 1 (DOCX 129 kb)


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Kristin N. Anderson
    • 1
  • Richard B. Schwab
    • 1
  • Maria Elena Martinez
    • 1
    • 2
  1. 1.Moores Cancer CenterUniversity of California, San DiegoLa JollaUSA
  2. 2.Department of Family and Preventive MedicineUniversity of California, San DiegoLa JollaUSA

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