Distinct reproductive risk profiles for intrinsic-like breast cancer subtypes: pooled analysis of population-based studies.
Jung AY., Ahearn TU., Behrens S., Middha P., Bolla MK., Wang Q., Arndt V., Aronson KJ., Augustinsson A., Beane Freeman LE., Becher H., Brenner H., Canzian F., Carey LA., CTS Consortium None., Czene K., Eliassen AH., Eriksson M., Evans DG., Figueroa JD., Fritschi L., Gabrielson M., Giles GG., Guénel P., Hadjisavvas A., Haiman CA., Håkansson N., Hall P., Hamann U., Hoppe R., Hopper JL., Howell A., Hunter DJ., Hüsing A., Kaaks R., Kosma V-M., Koutros S., Kraft P., Lacey JV., Le Marchand L., Lissowska J., Loizidou MA., Mannermaa A., Maurer T., Murphy RA., Olshan AF., Olsson H., Patel AV., Perou CM., Rennert G., Shibli R., Shu X-O., Southey MC., Stone J., Tamimi RM., Teras LR., Troester MA., Truong T., Vachon CM., Wang SS., Wolk A., Wu AH., Yang XR., Zheng W., Dunning AM., Pharoah PDP., Easton DF., Milne RL., Chatterjee N., Schmidt MK., García-Closas M., Chang-Claude J.
BACKGROUND: Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER) positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear. METHODS: Analyses included up to 23,353 cases, and 71,072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative) and by invasiveness. All statistical tests were 2-sided. RESULTS: Compared to nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2-like and HER2-enriched-like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46; for multiparous women with luminal A-like tumors 20-<25 years after last birth and 45-<50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95%CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95%CI = 0.79 to 1.34, for multiparous women 25 to