Parity, breastfeeding, and breast cancer risk by hormone receptor status and molecular phenotype: results from the Nurses’ Health Studies

BACKGROUND: Epidemiologic data suggest that parity increases risk of hormone receptor-negative breast cancer and that breastfeeding attenuates this association. Prospective data, particularly on the joint effects of higher parity and breastfeeding, are limited. METHODS: We investigated parity, breastfeeding, and breast cancer risk by hormone-receptor (estrogen (ER) and progesterone receptor (PR)) and molecular subtypes (luminal A, luminal B, HER2-enriched, and basal-like) in the Nurses’ Health Study (NHS; 1976–2012) and NHSII (1989–2013). A total of 12,452 (ER+ n = 8235; ER− n = 1978) breast cancers were diagnosed among 199,514 women. We used Cox proportional hazards models, adjusted for breast cancer risk factors, to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Parous women had lower risk of ER+ breast cancer (vs. nulliparous, HR = 0.82 [0.77–0.88]); no association was observed for ER− disease (0.98 [0.84–1.13]; P(het) = 0.03). Among parous women, breastfeeding was associated with lower risk of ER− (vs. never 0.82 [0.74–0.91]), but not ER+, disease (0.99 [0.94–1.05]; P(het) < 0.001). Compared to nulliparous women, higher parity was inversely associated with luminal B breast cancer regardless of breastfeeding (≥ 3 children: ever breastfed, 0.78 [0.62–0.98]; never breastfed, 0.76 [0.58–1.00]) and luminal A disease only among women who had breastfed (≥ 3 children, 0.84 [0.71–0.99]). Basal-like breast cancer risk was suggestively higher among women with higher parity who never breastfed; associations were null among those who ever breastfed. CONCLUSIONS: This study provides evidence that breastfeeding is inversely associated with hormone receptor-negative breast cancers, representing an accessible and cost-effective risk-reduction strategy for aggressive disease subtypes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13058-019-1119-y) contains supplementary material, which is available to authorized users.