Body Size and Risk of Luminal, HER2-Overexpressing, and Triple-Negative Breast Cancer in Postmenopausal Women

Although the clinical relevance of molecular subtypes of breast cancer has been documented, little is known about risk factors for different tumor subtypes, especially the HER2-overexpressing and the triple-negative subtypes that have poor prognoses. Obesity may be differentially related to the risk of different subtypes given the various potential mechanisms underlying its association with breast cancer. We pooled two population-based case-control studies of postmenopausal breast cancer for an analysis, including 1,447 controls and 1,008 luminal (hormone receptor positive), 39 HER2-overexpressing (hormone receptor negative, HER2 positive), and 77 triple-negative (hormone receptor and HER2 negative) cases. Associations between anthropometric factors and the risk of different breast cancer subtypes were evaluated using polytomous logistic regression. Among women not currently using menopausal hormone therapy, body mass index (BMI) and weight were associated with the risk of luminal tumors [odds ratio (OR) comparing highest versus lowest quartiles, 1.7; 95% confidence interval (95% CI), 1.2-2.4 and OR, 1.7; 95% CI, 1.2-2.4, respectively] and suggestively associated with risk of triple-negative tumors (OR, 2.7; 95% CI, 1.0-7.5 and OR, 5.1; 95% CI, 1.1-23.0, respectively). Neither BMI nor weight was associated with the risk of any tumor subtype among hormone therapy users. The positive relationship between BMI and luminal tumors among postmenopausal women not using hormone therapy is well characterized in the literature. Although our sample size was limited, body size may also be related to the risk of postmenopausal triple-negative breast cancer among nonusers of hormone therapy. Given the expanding obesity epidemic, the widespread cessation of hormone therapy use, and the poor prognosis of triple-negative tumors, this novel finding merits confirmation. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2078–86)