Important Role of Menarche in Development of Estrogen Receptor-Negative Breast Cancer in African American Women

J Natl Cancer Inst. 2015 Jun 17;107(9):djv172. doi: 10.1093/jnci/djv172. Print 2015 Sep.


Background: Menarche is a critical time point for diverging fates of mammary cells of origin. African American women have young age at menarche, which could be associated with their high rates of estrogen receptor-negative (ER-) breast cancer.

Methods: In the AMBER Consortium, using harmonized data from 4426 African American women with breast cancer and 17 474 controls, we used polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for ages at menarche and first live birth (FLB), and the interval between, in relation to ER+ and ER- breast cancer. All statistical tests were two-sided.

Results: Risk of ER- breast cancer was reduced with later age at menarche among both parous and nulliparous women (≥15 vs <11 years OR = 0.62, 95% CI = 0.48 to 0.81 and OR = 0.56, 95% CI = 0.29 to 1.10, respectively), with no effect of age at FLB. For ER+ breast cancer, the inverse association was weaker among nulliparous women. While longer intervals between menarche and FLB were associated with increased risk of ER+ breast cancer in a dose-response fashion (OR for 20 year interval = 1.39, 95% CI = 1.08 to 1.79, P trend = .003), ER- risk was only increased for intervals up to 14 years and not beyond (P trend = .33).

Conclusions: While ER- breast cancer risk was markedly reduced in women with a late age at menarche, there was not a clear pattern of increased risk with longer interval between menarche and FLB, as was observed for ER+ breast cancer. These findings indicate that etiologic pathways involving adolescence and pregnancy may differ for ER- and ER+ breast cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • African Americans / statistics & numerical data*
  • Age Factors
  • Aged
  • Breast Feeding
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / epidemiology*
  • Child
  • Confounding Factors, Epidemiologic
  • Female
  • Humans
  • Logistic Models
  • Menarche*
  • Menopause
  • Middle Aged
  • Odds Ratio
  • Parity
  • Pregnancy
  • Receptors, Estrogen / analysis*
  • Reproductive History*
  • Surveys and Questionnaires
  • United States / epidemiology


  • Receptors, Estrogen