Hypothesized role of pregnancy hormones on HER2+ breast tumor development

Giovanna I. Cruz, María Elena Martínez, Loki Natarajan, Betsy C. Wertheim, Manuela Gago-Dominguez, Melissa Bondy, Adrian Daneri-Navarro, María Mercedes Meza-Montenegro, Luis Enrique Gutierrez-Millan, Abenaa Brewster, Pepper Schedin, Ian K. Komenaka, J. Esteban Castelao, Angel Carracedo, Carmen M. Redondo, Patricia A. Thompson

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)237-246
Number of pages10
JournalBreast Cancer Research and Treatment
Volume137
Issue number1
DOIs
StatePublished - Jan 1 2013

Keywords

  • Breast cancer
  • Breast tumor subtypes
  • Etiologic heterogeneity
  • HER2
  • Hispanic
  • Parity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Cruz, G. I., Martínez, M. E., Natarajan, L., Wertheim, B. C., Gago-Dominguez, M., Bondy, M., Daneri-Navarro, A., Meza-Montenegro, M. M., Gutierrez-Millan, L. E., Brewster, A., Schedin, P., Komenaka, I. K., Castelao, J. E., Carracedo, A., Redondo, C. M., & Thompson, P. A. (2013). Hypothesized role of pregnancy hormones on HER2+ breast tumor development. Breast Cancer Research and Treatment, 137(1), 237-246. https://doi.org/10.1007/s10549-012-2313-0