Hypothesized role of pregnancy hormones on HER2+ breast tumor development

Breast Cancer Res Treat. 2013 Jan;137(1):237-46. doi: 10.1007/s10549-012-2313-0. Epub 2012 Nov 8.

Abstract

Breast cancer incidence rates have declined among older but not younger women; the latter are more likely to be diagnosed with breast cancers carrying a poor prognosis. Epidemiological evidence supports an increase in breast cancer incidence following pregnancy with risk elevated as much as 10 years post-partum. We investigated the association between years since last full-term pregnancy at the time of diagnosis (≤10 or >10 years) and breast tumor subtype in a case series of premenopausal Hispanic women (n = 627). Participants were recruited in the United States, Mexico, and Spain. Cases with known estrogen receptor (ER), progesterone receptor (PR), and HER2 status, with one or more full-term pregnancies ≥1 year prior to diagnosis were eligible for this analysis. Cases were classified into three tumor subtypes according to hormone receptor (HR+ = ER+ and/or PR+; HR- = ER- and PR-) expression and HER2 status: HR+/HER2-, HER2+ (regardless of HR), and triple negative breast cancer. Case-only odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for HER2+ tumors in reference to HR+/HER2- tumors. Participants were pooled in a mixed-effects logistic regression model with years since pregnancy as a fixed effect and study site as a random effect. When compared to HR+/HER2- cases, women with HER2+ tumors were more likely be diagnosed in the post-partum period of ≤10 years (OR = 1.68; 95 % CI, 1.12-2.52). The effect was present across all source populations and independent of the HR status of the HER2+ tumor. Adjusting for age at diagnosis (≤45 or >45 years) did not materially alter our results (OR = 1.78; 95 % CI, 1.08-2.93). These findings support the novel hypothesis that factors associated with the post-partum breast, possibly hormonal, are involved in the development of HER2+ tumors.

Publication types

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

MeSH terms

  • Adult
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / metabolism*
  • Female
  • Gonadal Steroid Hormones / physiology
  • Hispanic or Latino
  • Humans
  • Incidence
  • Logistic Models
  • Mexico / epidemiology
  • Middle Aged
  • Placental Hormones / physiology
  • Pregnancy
  • Premenopause
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Spain / epidemiology
  • United States / epidemiology
  • Young Adult

Substances

  • Gonadal Steroid Hormones
  • Placental Hormones
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2