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Reproductive and hormonal risk factors for postmenopausal luminal, HER-2-overexpressing, and triple-negative breast cancer†

  1. Amanda I. Phipps MPH1,2,‡,*,
  2. Kathleen E. Malone PhD1,2,
  3. Peggy L. Porter MD3,4,
  4. Janet R. Daling PhD1,2,
  5. Christopher I. Li MD, PhD1,2

Article first published online: 25 AUG 2008

DOI: 10.1002/cncr.23786

Issue

Cancer

Cancer

Volume 113, Issue 7, pages 1521–1526, 1 October 2008

Additional Information

How to Cite

Phipps, A. I., Malone, K. E., Porter, P. L., Daling, J. R. and Li, C. I. (2008), Reproductive and hormonal risk factors for postmenopausal luminal, HER-2-overexpressing, and triple-negative breast cancer. Cancer, 113: 1521–1526. doi: 10.1002/cncr.23786

Author Information

  1. 1

    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington

  2. 2

    Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, Washington

  3. 3

    Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington

  4. 4

    Department of Pathology, School of Medicine, University of Washington, Seattle, Washington

  1. ‡

    Fax: (206) 667-5948

*Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, PO Box 19024, Seattle, WA 98109-1024

  1. †

    The studies in the current analysis were both supported by the National Cancer Institute (NCI) through contracts with the Fred Hutchinson Cancer Research Center (R01 CA072787 and R01 CA85913). The work of A.I.P. in this publication was made possible by the National Center for Research Resources (NCRR; Grant No. 1 TL1 RR02501601), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research.

Publication History

  1. Issue published online: 17 SEP 2008
  2. Article first published online: 25 AUG 2008
  3. Manuscript Accepted: 15 MAY 2008
  4. Manuscript Revised: 6 MAY 2008
  5. Manuscript Received: 2 APR 2008

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Keywords:

  • breast cancer;
  • postmenopausal;
  • triple-negative;
  • luminal;
  • HER-2;
  • breastfeeding;
  • parity;
  • menarche

In this population-based, case–control study, associations between reproductive factors and breast cancer risk were estimated for subtypes of breast cancer distinguished by estrogen receptor (ER), progesterone receptor (PR), and HER-2 status. Prolonged breastfeeding was found to be associated with a significantly reduced risk of both luminal (ER–positive) and triple-negative (ER-negative [-]/PR-/HER-2-) breast cancers, and heterogeneity between subtype-specific associations was pronounced for many risk factors.

Abstract

BACKGROUND.

Molecular profiling studies have identified subtypes of breast cancer that can be approximately classified by estrogen receptor (ER), progesterone receptor (PR), and HER-2/neu (HER-2) expression. These molecular subtypes are prognostically significant, but to the authors' knowledge, differences in their etiologic profiles have not been established. Reproductive factors may plausibly be differentially correlated with the risk of different breast cancer subtypes because these factors are presumed to impact exposure to endogenous sex hormones.

METHODS.

The authors pooled 2 population-based, case–control studies of breast cancer in women ages 55 to 79 years for an analysis including 1476 controls and 1023 cases of luminal breast cancer, 39 cases of HER-2-overexpressing breast cancer, and 78 cases of triple-negative breast cancer. Polytomous logistic regression was used to compare each case group with controls.

RESULTS.

Associations varied by molecular subtype. Early age at menarche was only found to be associated with risk of HER-2-overexpressing disease (odds ratio [OR] of 2.7; 95% confidence interval [95% CI], 1.4-5.5), whereas breastfeeding for ≥6 months was only found to be protective for luminal and triple-negative disease (OR of 0.8 [95% CI, 0.6-1.0] and OR of 0.5 [95% CI, 0.3-0.9], respectively). Both late age at menopause and the use of estrogen plus progestin hormone therapy were only found to be associated with risk of luminal disease (OR of 1.6 [95% CI, 1.1-2.2] and OR of 1.7 [95% CI, 1.3-2.1], respectively). No differences in risks associated with parity or age at first live birth were observed by subtype.

CONCLUSIONS.

Certain reproductive factors may have a greater impact on the risk of certain molecular subtypes of disease compared with others. Future studies that further define the etiology of breast cancer subtypes will add to the biologic understanding of this disease. Cancer 2008. © 2008 American Cancer Society.

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