Abstract
BackgroundKi-67 expression is a possible risk biomarker and is currently being used as a response biomarker in chemoprevention trials. Mammographic breast density is a risk biomarker and is also being used as a response biomarker. We previously showed that Ki-67 expression is higher in specimens of benign breast cells exhibiting cytologic atypia that are obtained by random periareolar fine needle aspiration (RPFNA). It is not known whether there is a correlation between mammographic density and Ki-67 expression in benign breast ductal cells obtained by RPFNA.MethodsIncluded in the study were 344 women at high risk for developing breast cancer (based on personal or family history), seen at The University of Kansas Medical Center high-risk breast clinic, who underwent RPFNA with cytomorphology and Ki-67 assessment plus a mammogram. Mammographic breast density was assessed using the Cumulus program. Categorical variables were analyzed by χ2 test, and continuous variables were analyzed by nonparametric test and linear regression.ResultsForty-seven per cent of women were premenopausal and 53% were postmenopausal. The median age was 48 years, median 5-year Gail Risk was 2.2%, and median Ki-67 was 1.9%. The median mammographic breast density was 37%. Ki-67 expression increased with cytologic abnormality (atypia versus no atypia; P ≤ 0.001) and younger age (≤50 years versus >50 years; P ≤ 0.001). Mammographic density was higher in premenopausal women (P ≤ 0.001), those with lower body mass index (P < 0.001), and those with lower 5-year Gail risk (P = 0.001). Mammographic density exhibited no correlation with Ki-67 expression or cytomorphology.ConclusionGiven the lack of correlation of mammographic breast density with either cytomorphology or Ki-67 expression in RPFNA specimens, mammographic density and Ki-67 expression should be considered as potentially complementary response biomarkers in breast cancer chemoprevention trials.
Highlights
Established risk factors for the development of breast cancer include components incorporated into the Gail model, breast mammographic density, and cellular atypia
Given the lack of correlation of mammographic breast density with either cytomorphology or Ki-67 expression in random periareolar fine needle aspiration (RPFNA) specimens, mammographic density and Ki-67 expression should be considered as potentially complementary response biomarkers in breast cancer chemoprevention trials
In a cohort of 147 high risk women, we previously showed that cytomorphologic atypia in benign breast cells obtained by RPFNA is associated with increased Ki-67 expression [6]
Summary
Established risk factors for the development of breast cancer include components incorporated into the Gail model, breast mammographic density, and cellular atypia. A prospective study conducted in high-risk women employed random periareolar fine needle aspiration (RPFNA) to sample breast tissue [1]. It revealed that women with RPFNA atypia had a fivefold increased risk for subsequent clinical development of ductal carcinoma in situ (DCIS) or invasive cancer as compared with those without atypia, and RPFNA atypia stratified risk based on the Gail model [1]. We previously showed that Ki-67 expression is higher in specimens of benign breast cells exhibiting cytologic atypia that are obtained by random periareolar fine needle aspiration (RPFNA). It is not known whether there is a correlation between mammographic density and Ki-67 expression in benign breast ductal cells obtained by RPFNA
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