Cytomorphology and proliferation in breast epithelial cells obtained by random periareolar fine needle aspiration from obese postmenopausal women at high risk for development of breast cancer.

A16

Obesity, generally defined as a Body Mass Index (BMI) of greater than 28 Kg/m², is considered a risk factor for development of breast cancer in postmenopausal women. A biomarker modulation trial is planned wherein women at high risk for development of breast cancer on the basis of personal or family history and with a BMI >28 Kg/m² and >33% body fat by electrical impedance will undergo random periareolar fine needle aspiration (RPFNA) for procurement of breast epithelial cells. Women who satisfy eligibility requirements for cytomorphology (hyperplasia, with or without atypia) and proliferation (Ki-67 immunocytochemical expression in ≥1.5% of cells) will enroll in an intervention of diet and exercise, employing proven techniques of pre-packaged meals and behavioral counseling. After 6 months, a repeat RPFNA will be performed and changes in proliferation (primary endpoint) and cytomorphology will be assessed. Mammographic breast density and certain blood chemistry and serum hormone assays will also be evaluated. In preparation for this trial, we wished to determine whether women with BMI >28 Kg/m² displayed different cytologic characteristics than did women with a lower BMI. We also needed to define the proportion of potentially eligible high risk women that would be eligible for this study. Thus, we examined the cytologic and proliferation characteristics of postmenopausal women undergoing RPFNA in the Breast Cancer Prevention Center at the University of Kansas Medical Center between January 2003 and September 2005. Specimens from 177 women were evaluable for cytomorphology and proliferation, which was generally only attempted if there was greater than 500 epithelial cells per slide, which in turn was associated with a cytomorphologic characterization of hyperplasia. Sixty-eight women (38%) exhibited a BMI >28 Kg/m². There were no statistically significant differences between groups with high vs. low BMI for the endpoints of 5-year Gail risk of developing breast cancer (medians of 2.7% vs. 2.6%), frequency of atypia (32% vs 25%), semi-quantitative Masood cytology index score (median of 14), cell number per slide (median of 1000-5000 cells) or percent cells positive for Ki-67 expression (medians of 1.3% vs. 1.2%). For the eligibility requirement of measurable proliferation, 45% of all women for whom Ki-67 assessment was attempted did exhibit K-67 expression in ≥ 1.5% of cells, with 46% for women with low BMI and 44% for women with high BMI. We conclude that postmenopausal high risk women with a BMI >28 Kg/m² do not differ significantly from women with lower BMI in respect to the cytologic characteristics of breast epithelial cells acquired by RPFNA. Secondly, we anticipate that a substantial proportion of women screened for the planned intervention trial will meet the eligibility requirements.