Cancer Causes & Control

, Volume 22, Issue 3, pp 399–405 | Cite as

Reproductive history and risk of three breast cancer subtypes defined by three biomarkers

  • Amanda I. PhippsEmail author
  • Diana S. M. Buist
  • Kathleen E. Malone
  • William E. Barlow
  • Peggy L. Porter
  • Karla Kerlikowske
  • Christopher I. Li
Original paper


Breast cancer subtypes defined by estrogen receptor (ER), progesterone receptor (PR), and HER2 expression are biologically distinct and thus, may have distinct etiologies. In particular, it is plausible that risk factors operating through hormonal mechanisms are differentially related to risk of such tumor subtypes. Using data from the Breast Cancer Surveillance Consortium, we explored associations between reproductive history and three breast cancer subtypes. Data on parity and age at first birth were collected from 743,623 women, 10,896 of whom were subsequently diagnosed with breast cancer. Cases were classified into three subtypes based on tumor maker expression: (1) ER positive (ER+, N = 8,203), (2) ER negative/PR negative/HER2 positive (ER−/PR−/HER2+, N = 288), or (3) ER-, PR-, and HER2-negative (triple-negative, N = 645). Associations with reproductive history, evaluated using Cox regression, differed significantly across tumor subtypes. Nulliparity was most strongly associated with risk of ER+ breast cancer [hazard ratio (HR) = 1.31, 95% confidence interval (CI): 1.23–1.39]; late age at first birth was most strongly associated with risk of ER-/PR-/HER2+ disease (HR = 1.83, 95% CI: 1.31–2.56). Neither parity nor age at first birth was associated with triple-negative breast cancer. In contrast to ER+ and ER−/PR−/HER2+ subtypes, reproductive history does not appear to be a risk factor for triple-negative breast cancer.


Breast cancer Parity Age at first birth Triple-negative 



We thank the participating women, mammography facilities, and radiologists for the data they have provided for this study. A list of the BCSC investigators and procedures for requesting BCSC data for research purposes are provided at: This work was supported by a NCI-funded Breast Cancer Surveillance Consortium co-operative agreement (U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040). The collection of cancer data used in this study was supported in part by several state public health departments and cancer registries throughout the United States. For a full description of these sources, please see: This publication was supported by grant numbers T32 CA09168 and R25-CA94880 from the NCI, NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCI, NIH.


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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Amanda I. Phipps
    • 1
    • 2
    Email author
  • Diana S. M. Buist
    • 2
    • 3
  • Kathleen E. Malone
    • 1
    • 2
  • William E. Barlow
    • 2
    • 3
    • 4
  • Peggy L. Porter
    • 1
    • 5
  • Karla Kerlikowske
    • 6
  • Christopher I. Li
    • 1
    • 2
  1. 1.Division of Public Health SciencesFred Hutchinson Cancer Research CenterSeattleUSA
  2. 2.School of Public HealthUniversity of WashingtonSeattleUSA
  3. 3.Group Health Research InstituteSeattleUSA
  4. 4.Cancer Research and BiostatisticsSeattleUSA
  5. 5.School of MedicineUniversity of WashingtonSeattleUSA
  6. 6.Departments of Medicine and Epidemiology and BiostatisticsUniversity of CaliforniaSan FranciscoUSA

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