Obesity and Angiolymphatic Invasion in Primary Breast Cancer.

Background and Objectives: Obesity is associated both with higher rates of breast cancer and with unfavorable breast cancer outcomes. Small studies have suggested that obesity may be associated with unfavorable tumor biologic characteristics, such as angiolymphatic invasion. The purpose of this study was to characterize the independent association of obesity with the presence of angiolymphatic invasion, stage at presentation, estrogen receptor (ER) status, the triple-negative phenotype, and tumor grade after controlling for clinical factors.Methods: Detailed clinical and pathologic data were abstracted from the medical records of all 1361 patients with 1398 Stage I, II, or III primary breast cancers who had breast surgery at the University of Michigan Comprehensive Cancer Center between January 1, 2000 and December 31, 2006. A second abstractor, who did not have access to the clinical and pathologic tumor characteristics, collected patient height and weight. Bivariate and multivariate analyses were conducted to investigate the relationships between body mass index (BMI) and tumor biologic features controlling for menopausal status, comorbid diabetes and hypertension, use of hormone replacement therapy before the diagnosis of breast cancer, race, and ethnicity. Results: In bivariate analyses, obesity was not associated with hormone receptor status, HER2 status, triple-negative phenotype, or histologic grade. There was a borderline significant association between obesity category and the presence of angiolymphatic invasion (p = 0.06) in the sample of 1398 tumors, severely obese women being the most likely to have angiolymphatic invasion. Among pre- and perimenopausal women, the likelihood of angiolymphatic invasion in the tumors varied by obesity category (p = 0.02) with angiolymphatic invasion more likely in obese (20.0%) compared with the tumors of healthy weight (14.4%) women. In multivariate analyses, obesity status was independently associated with the presence of angiolymphatic invasion (joint test of significance, p = 0.04) after controlling for menopausal status, use of hormone replacement therapy at the time of diagnosis, diabetes and hypertension, and tumor features, including grade, stage, estrogen receptor status, and HER2 status. Obesity was associated with lower odds of triple-negative disease (odds ratio, OR, among severely obese women 0.37, 95% C.I. 0.15 – 0.92). There were significant associations between diabetes and tumor biology in multivariate analyses restricted to tumors in pre- and perimenopausal women. Diabetes was associated with ER-negative tumor status (OR 5.66, 95% C.I. 1.05 to 30.55) and with the triple-negative phenotype (OR 13.73, 95% C.I. 2.23 to 84.50).Discussion: In this large sample of invasive breast cancers, obesity was independently associated with the presence of angiolymphatic invasion. Furthermore, diabetes was found to be associated with ER-negative and triple-negative breast cancer among premenopausal women. Higher rates of angiolymphatic invasion among obese women may account in part for the poorer outcomes among obese women with breast cancer, and higher rates of triple-negative breast cancer may account for poorer outcomes among women with diabetes. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5151.