TY - JOUR
T1 - Hypothesized role of pregnancy hormones on HER2+ breast tumor development
AU - Cruz, Giovanna I.
AU - Martínez, María Elena
AU - Natarajan, Loki
AU - Wertheim, Betsy C.
AU - Gago-Dominguez, Manuela
AU - Bondy, Melissa
AU - Daneri-Navarro, Adrian
AU - Meza-Montenegro, María Mercedes
AU - Gutierrez-Millan, Luis Enrique
AU - Brewster, Abenaa
AU - Schedin, Pepper
AU - Komenaka, Ian K.
AU - Castelao, J. Esteban
AU - Carracedo, Angel
AU - Redondo, Carmen M.
AU - Thompson, Patricia A.
N1 - Funding Information:
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.
PY - 2013/1
Y1 - 2013/1
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Breast tumor subtypes
KW - Etiologic heterogeneity
KW - HER2
KW - Hispanic
KW - Parity
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UR - http://www.scopus.com/inward/citedby.url?scp=84871735036&partnerID=8YFLogxK
U2 - 10.1007/s10549-012-2313-0
DO - 10.1007/s10549-012-2313-0
M3 - Article
C2 - 23135573
AN - SCOPUS:84871735036
SN - 0167-6806
VL - 137
SP - 237
EP - 246
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 1
ER -