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Hypothesized role of pregnancy hormones on HER2+ breast tumor development

  • Epidemiology
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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.

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Acknowledgments

This study was supported by a grant from the National Cancer Institute (UO1CA153086); a Susan G. Komen for the Cure® Post-baccalaureate Training in Disparities Research Grant (KG090934); the Avon Foundation; a supplement to the Arizona Cancer Center Core Grant from the National Cancer Institute (CA-023074-2953); a supplement to the M.D. Anderson Cancer Center SPORE in Breast Cancer (P50 CA116199-02S1); FIS Intrasalud (PS09/02368); Programa Grupos Emergentes EMER ISCIII, Instituto de Salud Carlos III, Servicio Galego Saúde (SERGAS), Oncology and Genetics Unit. Complejo Hospitalario Universitario de Vigo, Spain; and the Botin Foundation. We are indebted to Ana Lilia Amador, Leticia Cordova, Carole Kepler, and Fang Wang for their contribution.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. School of Public Health, University of California, Berkeley, Berkeley, CA, USA

    Giovanna I. Cruz

  2. Moores UCSD Cancer Center, University of California, San Diego, La Jolla, CA, USA

    María Elena Martínez & Loki Natarajan

  3. Arizona Cancer Center, University of Arizona, Tucson, AZ, USA

    Betsy C. Wertheim

  4. Genomic Medicine Group, Galician Foundation of Genomic Medicine, Complejo Hospitalario Universitario de Santiago, SERGAS, IDIS, Santiago de Compostela, Spain

    Manuela Gago-Dominguez & Angel Carracedo

  5. Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA

    Melissa Bondy

  6. Universidad de Guadalajara, Guadalajara, Mexico

    Adrian Daneri-Navarro

  7. Instituto Tecnológico de Sonora, Ciudad Obregon, Mexico

    María Mercedes Meza-Montenegro

  8. Universidad de Sonora, Hermosillo, Mexico

    Luis Enrique Gutierrez-Millan

  9. Department of Clinical Cancer Prevention, M.D. Anderson Cancer Center, University of Texas, Houston, TX, USA

    Abenaa Brewster

  10. Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Denver, CO, USA

    Pepper Schedin

  11. Department of Surgery, Maricopa Medical Center, Phoenix, AZ, USA

    Ian K. Komenaka

  12. Oncology and Genetics Unit, Genomic Medicine Group, SERGAS, Complejo Hospitalario Universitario de Vigo, Vigo, Spain

    J. Esteban Castelao & Carmen M. Redondo

  13. Department of Cellular and Molecular Medicine, College of Medicine, University of Arizona, Arizona Cancer Center, 1515 N. Campbell Ave, P.O. Box 245024, Tucson, AZ, 85724, USA

    Patricia A. Thompson

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  1. Giovanna I. Cruz
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Cruz, G.I., Martínez, M.E., Natarajan, L. et al. Hypothesized role of pregnancy hormones on HER2+ breast tumor development. Breast Cancer Res Treat 137, 237–246 (2013). https://doi.org/10.1007/s10549-012-2313-0

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