title: Hypothesized role of pregnancy hormones on HER2+ breast tumor development.
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.
authors.affiliation: School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
authors.forename: Giovanna I
authors.initials: GI
authors.lastname: Cruz
authors.forename: María Elena
authors.initials: ME
authors.lastname: Martínez
authors.forename: Loki
authors.initials: L
authors.lastname: Natarajan
authors.forename: Betsy C
authors.initials: BC
authors.lastname: Wertheim
authors.forename: Manuela
authors.initials: M
authors.lastname: Gago-Dominguez
authors.forename: Melissa
authors.initials: M
authors.lastname: Bondy
authors.forename: Adrian
authors.initials: A
authors.lastname: Daneri-Navarro
authors.forename: María Mercedes
authors.initials: MM
authors.lastname: Meza-Montenegro
authors.forename: Luis Enrique
authors.initials: LE
authors.lastname: Gutierrez-Millan
authors.forename: Abenaa
authors.initials: A
authors.lastname: Brewster
authors.forename: Pepper
authors.initials: P
authors.lastname: Schedin
authors.forename: Ian K
authors.initials: IK
authors.lastname: Komenaka
authors.forename: J Esteban
authors.initials: JE
authors.lastname: Castelao
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Redondo
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Thompson
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology / Q000378:metabolism*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology; D006630:Hispanic or Latino; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D010926:Placental Hormones / Q000502:physiology; D011247:Pregnancy; D017697:Premenopause; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013030:Spain / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D012739:Gonadal Steroid Hormones; D010926:Placental Hormones; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human