Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study
Couplée à la cohorte européenne EPIC, cette étude prospective incluant 4 607 participantes évalue l'association entre l'adiposité, l'utilisation d'un traitement hormonal substitutif de la ménopause et le risque de cancer du sein, en fonction de l'âge et du statut du récepteur hormonal
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.