Reproductive history and oral contraceptive use in relation to risk of triple-negative breast cancer

Amanda I. Phipps, Rowan T. Chlebowski, Ross Prentice, Anne McTiernan, Jean Wactawski-Wende, Lewis H. Kuller, Lucile L. Adams-Campbell, Dorothy Lane, Marcia L. Stefanick, Mara Vitolins, Geoffrey C. Kabat, Thomas E. Rohan, Christopher I. Li

Research output: Contribution to journalArticlepeer-review

177 Scopus citations

Abstract

Background Triple-negative (ie, estrogen receptor [ER], progesterone receptor, and HER2 negative) breast cancer occurs disproportionately among African American women compared with white women and is associated with a worse prognosis than ER-positive (ER+) breast cancer. Hormonally mediated risk factors may be differentially related to risk of triple-negative and ER+ breast cancers. Methods Using data from 155723 women enrolled in the Women's Health Initiative, we assessed associations between reproductive and menstrual history, breastfeeding, oral contraceptive use, and subtype-specific breast cancer risk. We used Cox regression to evaluate associations with triple-negative (N = 307) and ER+ (N = 2610) breast cancers and used partial likelihood methods to test for differences in subtype-specific hazard ratios (HRs). Results Reproductive history was differentially associated with risk of triple-negative and ER+ breast cancers. Nulliparity was associated with decreased risk of triple-negative breast cancer (HR = 0.61, 95% confidence interval [CI] = 0.37 to 0.97) but increased risk of ER+ breast cancer (HR = 1.35, 95% CI = 1.20 to 1.52). Age-adjusted absolute rates of triple-negative breast cancer were 2.71 and 1.54 per 10000 person-years in parous and nulliparous women, respectively; by comparison, rates of ER+ breast cancer were 21.10 and 28.16 per 10000 person-years in the same two groups. Among parous women, the number of births was positively associated with risk of triple-negative disease (HR for three births or more vs one birth = 1.46, 95% CI = 0.82 to 2.63) and inversely associated with risk of ER+ disease (HR = 0.88, 95% CI = 0.74 to 1.04). Ages at menarche and menopause were modestly associated with risk of ER+ but not triple-negative breast cancer; breastfeeding and oral contraceptive use were not associated with either subtype. Conclusion The association between parity and breast cancer risk differs appreciably for ER+ and triple-negative breast cancers. These findings require further confirmation because the biological mechanisms underlying these differences are uncertain.

Original languageEnglish (US)
Pages (from-to)470-477
Number of pages8
JournalJournal of the National Cancer Institute
Volume103
Issue number6
DOIs
StatePublished - Mar 16 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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