Association between body mass index and risk of breast cancer according to breast cancer subtypes: A systematic review and meta-analysis

Background: Higher body mass index (BMI) is a risk factor for breast cancer (BC) development, but the relationship with BC subtypes in pre- and post-menopausal women remains unclear. Methods: We performed a systematic search from PubMed, Embase and Cochrane databases until 09/24 (CRD42020206108) for cohort and case-control studies assessing the association between BMI and BC subtypes and/or menopausal status. BC risk in overweight (BMI 25–29.9 kg/m2) or obese (BMI≥30 kg/m2) subjects was compared to risk in under/normal weight (BMI<25 kg/m2). BC subtypes were classified as i) ER-positive (regardless HER2-status) ii) ER-negative (regardless HER2-status) iii) HER2-positive (regardless ER-status); iv) triple-negative BC (TNBC). Results: Out of 2841 records screened, 33 studies (9 cohort and 24 case-control) including 2,103,181 women were eligible. Obesity was associated with a modestly increased risk of ER-positive BC (pOR 1.13; 95 % CI 1.03–1.24). In postmenopausal women, obesity was associated with a moderate higher risk of ER-positive BC (pOR 1.29; 95 % CI 1.18–1.41), while overweight was associated with an increased risk of ER-positive (pOR 1.14; 95 % CI 1.06–1.22) and HER2-positive BC (pOR 1.13; 95 % CI 1.05–1.22). In premenopausal women, overweight was linked with reduced risk of ER-positive (pOR 0.80 95 % CI 0.71–0.91) but increased risk of ER-negative BC (pOR 1.15 95 % CI 1.05–1.26) and TNBC (pOR 1.30; 95 % CI 1.15–1.47). Conclusions: Obesity was associated with a modestly higher risk of ER-positive BC, driven by postmenopausal status. Considering potential confounders, in premenopausal women, higher BMI was associated with lower risk of ER-positive BC, and an increased risk of ER-negative BC.