Breast Cancer Research and Treatment

, Volume 137, Issue 2, pp 579–587 | Cite as

Reproductive factors and risk of estrogen receptor positive, triple-negative, and HER2-neu overexpressing breast cancer among women 20–44 years of age

  • Christopher I. LiEmail author
  • Elisabeth F. Beaber
  • Mei-Tzu Chen Tang
  • Peggy L. Porter
  • Janet R. Daling
  • Kathleen E. Malone


Aspects of reproductive history are among the most well-established breast cancer risk factors. However, relatively little is known about how they influence risk of different molecular subtypes of breast cancer, particularly among younger women. Using data from a population-based case–control study of women 20–44 years of age, we assessed the relationships between various reproductive factors and risk of estrogen receptor positive (ER+), triple-negative, and HER2-overexpressing breast cancers. Detailed reproductive histories were obtained through structured interviewer administered in-person questionnaires. Reproductive histories among control women (n = 941) were compared to those of ER+ cases (n = 781), triple-negative cases (n = 180), and HER2-overexpressing cases (n = 60) using polytomous logistic regression. Age at menarche, parity, and number of full-term pregnancies were similarly associated with risk of all three breast cancer subtypes. In contrast, age at first live birth, the interval between age at menarche and age at first birth, and breastfeeding were inversely associated with risk of triple-negative breast cancer (P values for trend 0.002, 0.006 and 0.018, respectively), but were not associated with risk of ER+ or HER2-overexpressing cancers. A strong inverse association between breastfeeding and risk of triple-negative breast cancer has now been consistently observed across numerous studies, and at present it is the most well-established protective factor for this aggressive and lethal form of breast cancer. Further studies clarifying the biological mechanisms underlying this relationship and confirming our results with respect to age at first birth and the interval between age at menarche and age at first birth are needed.


Breast cancer Triple-negative Estrogen receptor Reproductive factors 



This study was funded by the National Cancer Institute (R01-CA105041 and ARRA supplement to R01-CA10541) and the Department of Defense Breast Cancer Research Program (W81XWH-05-1-0482). The authors also wish to acknowledge the substantial contributions of Kristine Wicklund, Christabel Fowler, and Anne Oswald in the conduct of this research study. Other staff members making important contributions to this work are: Nancy Blythe, Ann Bradshaw, Dante del Pilar, Nicole Donovan, Fran Fleck, Joia Hicks, Amy Hoffman, Dick Jacke, Kristine Maddux, Evan McKay, Susan McKeeth, Sarah Moore, Kathryn Nord, Patty Pride, Georgene Ranney, Tiffany Silver-Brace, Camille Taylor, Jodi Thiel, Loni Tipton, and Margaret Trzyna. Lastly, we want to acknowledge the time and generosity of all of the women who participated in this research.


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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Christopher I. Li
    • 1
    Email author
  • Elisabeth F. Beaber
    • 1
  • Mei-Tzu Chen Tang
    • 1
  • Peggy L. Porter
    • 1
    • 2
  • Janet R. Daling
    • 1
  • Kathleen E. Malone
    • 1
  1. 1.Division of Public Health SciencesFred Hutchinson Cancer Research CenterSeattleUSA
  2. 2.Division of Human BiologyFred Hutchinson Cancer Research CenterSeattleUSA

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