Biomarker and cytologic abnormalities in women at high and low risk for breast cancer

Abstract

Fine needle aspirates (FNA) from 106 high-risk women and 25 low-risk women were evaluated for overexpression of estrogen receptor (ER), epidermal growth factor receptor (EGFR), mutant p53, and HER-2/neu by immunocytochemistry, and for aneuploidy by image analysis. Aspirates were also classified cytologically as normal, apocrine metaplasia, epithelial hyperplasia (EH), or dysplasia. High-risk women were those with a first-degree relative with breast cancer (76%), precancerous breast disease (26%), prior cancer of the contralateral breast (9%), or multiple abnormalities (I1 %). Low-risk women had none of the above risk factors, nor a prior breast biopsy or clinical evidence of fibrocystic disease. The median 10-year Gail risk for the high-risk group was 4%, compared to 0.7% for the low-risk group. There were significant differences (p < 0.01) between high-and low-risk women in the prevalences of hyperplasia (55% versus 12%), dysplasia (19% versus O%), aneuploidy (32% versus O%), overexpressed EGFR (32% versus 4%), and overexpressed p53 (29% versus 4%). The prevalence of multiple biomarker abnormalities was also greater in high-risk than in low-risk women (28% versus 0%; p < 0.01). Four percent (4%) of FNAs from high-risk women with normal cytology, 29% of aspirates with hyperplastic cytology, and 60% of those with dysplasia were associated with two or more biomarker abnormalities. The differences in the prevalence of multiple biomarker abnormalities among various cytologic categories were statistically significant (p = 0.02, normal versus EH; p = 0.02, EH versus dysplasia; p < 0.01, normal versus dysplasia). Further study of these tissue biomarkers as potential intermediate-term (5-10 year) predictors of breast cancer development is warranted. 0 1993 Wiley-Liss, Inc.Key words: Aneuploidy, biomarkers, breast cancer, dysplasia, epidermal growth factor receptor, estrogen receptor, fine needle aspirates, HER-2, high-risk, hyperplasia, p53We chose to study cytology, ploidy, and overexpression of estrogen receptor (ER), epidermal growth factor receptor (EGFR), p53, and HER-2/neu as potential tissue-derived predictors of later breast cancer development. Our rationale in Selecting these for study is that abnormalities Of all these variables are present in 240% of cases of

Breast cancer chemoprevention trials using the fine-needle aspiration model

“…E-mail: bfkimler@kumc.edu atypia) than are women who do not possess any recognized risk factors [Zalles et al, 1995]. Similarly, we have observed [Fabian et al, 1993[Fabian et al, , 1994[Fabian et al, , 1997a that the five biomarkers are abnormally expressed (i.e., DNA aneuploidy and immunocytochemical overexpression) in the high-risk women, whereas they are uncommon in the low-risk group. Abnormal biomarker expression, in turn, is associated with cytologic abnormality, being most common in FNAs that demonstrate hyperplasia with atypia.…”

“…The procedures for aspiration, tissue processing, and biomarker analysis have been previously detailed [Fabian et al, 1993[Fabian et al, , 1994[Fabian et al, , 1996[Fabian et al, , 1997cZalles et al, 1995]. Markers studied included cytologic morphology characterization, DNA ploidy, and immunocytochemical expression of p53 [Kamel et al, 1998], epidermal growth factor receptor (EGFR), estrogen receptor (ER), and Her-2/neu.…”

Molecular Pathology Assays for Breast Cancer

“…Identification of aneuploidy and abnormal expression of several markers (ER, EGFR, HER-2/neu, p53) has been reported in fine-needle aspirates of "normal" breast in women at higher risk for developing breast cancer (family history or previous atypical or neoplastic breast biopsy) than women at lower risk. 306 These data are very early, however. Chemoprevention biomarkers should be related to the mechanism of action of the therapeutic agent to be tested (e.g., PR expression in an antiestrogen trial) and should be identifiable in precancerous breast tissue.…”

Ductal lavage and its histopathologic basis: A cautionary tale

“…Following the initial work of Skolnick et al, 35.36 Fabian et al 37,38 performed random periareolar FNAs in high-risk women for detection of early cancer and risk stratification. The patients enrolled in the study were 30 -60 yr of age with a high risk for breast cancer as predicted by the Gail model (median 4%) with a control low-risk group.…”