Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study.

International audienceABSTRACT: INTRODUCTION: Associations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use. METHODS: Within the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen receptor (ER)-progesterone receptor (PR)- (n=1,021) and ER+PR+ (n=3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed. RESULTS: For risk of ER-PR- tumors, there was no association of BMI across the age bands. However, when analyses were restricted to postmenopausal HRT never users, a positive risk association with BMI (3rd versus 1st tertile HR=1.47[1.01-2.15]) was observed. BMI was inversely associated with ER+PR+ tumors among women aged [less than or equal to]49 years (per 5kg/m2 increase, HR=0.79[95%CI 0.68-0.91]), and positively associated with risk among women [greater than or equal to]65 years (HR=1.25[1.16-1.34]). Adjusting for BMI, waist and hip circumferences showed no further associations with risks of breast cancer subtypes. Current use of HRT was significantly associated with an increased risk of receptor-negative (HRT current use compared to HRT never use HR: 1.30[1.05-1.62]) and positive tumors (HR: 1.74[1.56-1.95]), although this risk increase was weaker for ER-PR- disease (Phet=0.035). The association of HRT was significantly stronger in the leaner women (BMI [less than or equal to]22.5kg/m2) than for more overweight women (BMI [greater than or equal to]25.9kg/m2) for, both, ER-PR- (HR: 1.74[1.15-2.63]) and ER+PR+ (HR: 2.33[1.84-2.92]) breast cancer and was not restricted to any particular HRT regime. CONCLUSIONS: An elevated BMI may be positively associated with risk of ER-PR- tumors, among postmenopausal women who never used HRT. Furthermore, postmenopausal HRT users were at an increased risk of ER-PR- as well as ER+PR+ tumors, especially among leaner women. For HR-positive tumors, but not for HR-negative tumors, our study confirms an inverse association of risk with BMI among young women of premenopausal age. Our data provide evidence for a possible role of sex hormones in the etiology of HR-negative tumors