Cj. Fabian et al., IDENTIFICATION OF A CHEMOPREVENTION COHORT FROM A POPULATION OF WOMENAT HIGH-RISK FOR BREAST-CANCER, Journal of cellular biochemistry, 1996, pp. 112-122
In a prospective pilot study, we performed breast fine needle aspirati
ons (FNAs) on 213 high-risk and 30 low-risk women and analyzed these a
spirates for cytologic changes and biomarker abnormalities of aneuploi
dy and overexpressed estrogen receptor (ER), epidermal growth factor r
eceptor (EGFR), p53 and HER-2/neu. High-risk women were those with a f
irst degree relative with breast cancer (73%), prior biopsy indicating
premalignant breast disease (26%), a history of breast cancer (13%),
or some multiple of these risk factors (11%). Median ages of the high-
risk and low-risk groups were 44 and 42, respectively. Sixty-three per
cent of the high-risk and 73% of the low-risk group were premenopausal
. Sixty-eight percent of the high-risk and 17% of low-risk women had c
ytologic evidence of hyperplasia with or without atypia (P<.0001). Ane
uploidy and overexpression of EGFR and p53 occurred in 25%, 36%, and 2
8% of high-risk subjects but in less than 4% of low-risk subjects (P<.
0002). Overexpression of ER and HER-2/neu occurred in 8% and 19%, resp
ectively of high-risk women; no low-risk women had these abnormalities
. Sixty-eight percent of high-risk women and 7% of low-risk women had
abnormalities of one or more of these biomarkers exclusive of cytology
. Thirty-one percent of high-risk women, but no low-risk women had abn
ormalities of two or more biomarkers (P=.0004). Biomarker abnormalitie
s were more frequent with increasing cytologic abnormality. Eighteen p
ercent of women with normal cytology, 29% of women with epithelial hyp
erplasia and 60% of women with hyperplasia with atypia had abnormaliti
es of two or more biomarkers (P=.048 and <.0001, respectively). Restri
cting the analysis to those three biomarkers most frequently overexpre
ssed in the high-risk group (ploidy, EGFR, p53), 13% of high-risk wome
n with normal cytology, 20% of high-risk women with epithelial hyperpl
asia and 51% of high-risk women with atypical hyperplasia had abnormal
ities of 2 or more of these 3 biomarkers. At a median follow up of two
years, 8 of 213 women have been diagnosed with in situ (n=5) or invas
ive (n=3) cancer. Later detection of neoplasia was associated with pri
or FNA evidence of atypical hyperplasia (P <.0001) and multiple biomar
ker abnormalities in the 5 test battery (P=.006) by univariate analysi
s. By multivariate analysis, development and/or detection of cancer wa
s primarily predicted by atypical hyperplasia (P=.0047) and secondaril
y by multiple biomarker abnormalities (P=0.021). Atypical hyperplasia,
ECFR, and p53 in breast FNAs have promise as risk markers and as surr
ogate endpoint biomarkers for breast cancer chemoprevention trials. (C
) 1997 Wiley-Liss, Inc.