Reproductive factors and risk of hormone receptor positive and negative breast cancer: a cohort study

Abstract

BackgroundThe association of reproductive factors with hormone receptor (HR)-negative breast tumors remains uncertain.MethodsWithin the EPIC cohort, Cox proportional hazards models were used to describe the relationships of reproductive factors (menarcheal age, time between menarche and first pregnancy, parity, number of children, age at first and last pregnancies, time since last full-term childbirth, breastfeeding, age at menopause, ever having an abortion and use of oral contraceptives [OC]) with risk of ER-PR- (n = 998) and ER+PR+ (n = 3,567) breast tumors.ResultsA later first full-term childbirth was associated with increased risk of ER+PR+ tumors but not with risk of ER-PR- tumors (≥35 vs. ≤19 years HR: 1.47 [95% CI 1.15-1.88] ptrend < 0.001 for ER+PR+ tumors; ≥35 vs. ≤19 years HR: 0.93 [95% CI 0.53-1.65] ptrend = 0.96 for ER-PR- tumors; P het = 0.03). The risk associations of menarcheal age, and time period between menarche and first full-term childbirth with ER-PR-tumors were in the similar direction with risk of ER+PR+ tumors (phet = 0.50), although weaker in magnitude and statistically only borderline significant. Other parity related factors such as ever a full-term birth, number of births, age- and time since last birth were associated only with ER+PR+ malignancies, however no statistical heterogeneity between breast cancer subtypes was observed. Breastfeeding and OC use were generally not associated with breast cancer subtype risk.ConclusionOur study provides possible evidence that age at menarche, and time between menarche and first full-term childbirth may be associated with the etiology of both HR-negative and HR-positive malignancies, although the associations with HR-negative breast cancer were only borderline significant.

Associations between Estrogen Receptor–Negative Breast Cancer and Timing of Reproductive Events Differ between African American and European American Women

“…Associations were strongest for age at menarche among AA women, with a 43% reduction in odds of ER- breast cancer with menarche at or after 14 years of age. Our findings of no differential associations by ER status and age at menarche among EA women are consistent with recent results from studies of primarily white premenopausal women (5), European women (6) and Mexican and Mexican-American women (7). However, our findings of strongly decreased risk of ER- breast cancer with later age at menarche among AA women are novel and need replication, as well as further examination of the driving forces behind these associations in AA women.…”

“…Until recently, there have been few explanations for these differences in tumor biology between EA and AA women, but there is accumulating evidence suggesting that differences in parity and in breastfeeding could contribute to these disparities (2-4), with parity associated with reduced risk of ER+ breast cancer, but increased risk of ER- tumors (reviewed in (3). In several studies, younger age at first live birth (FLB) has also been associated with reduced risk of ER+, but increased risk of ER- breast cancer (5,6), although there are conflicting data, as recently reviewed by Martinez and colleagues (7). …”

Reproductive risk factors and breast cancer subtypes: a review of the literature

“…Older age at menopause was positively associated with HR+ breast cancer in 3 of 7 studies [21, 28, 34]. The interval between age at menarche and age at first pregnancy was examined in four studies included in this review [15, 27, 31, 32], with three finding that a short interval was significantly inversely associated with HR+ breast cancer [27, 31, 32]. …”

AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2014

“…With the exception of a total fat intake that might increase the body mass index (BMI) and thus the breast cancer risk, there is no convincing data that the intake of fruits and vegetables, micronutrients, trace elements, or vitamins may reduce the breast cancer risk [3,4]. However, prevention of diabetes mellitus type II could reduce breast cancer incidence and mortality [5].…”