ESTROGEN-RECEPTOR EXPRESSION IN BENIGN BREAST EPITHELIUM AND BREAST-CANCER RISK

Background: Estrogen exposure is a major risk factor for breast cancer , Increased estrogen responsiveness of breast epithelium may enhance t his effect. We examined the relationship between breast cancer diagnos is and 1) the presence and absence of estrogen receptor expression in benign breast epithelium, 2) the level of expression and 3) its variat ion during the menstrual cycle, and 4) other established risk factors, e.g., age, age at menarche, parity, and family history, Methods: We m easured estrogen receptor expression (as % of positive cells) by immun ohistochemistry in normal breast epithelium from 376 women undergoing diagnostic or therapeutic breast surgery, Data on established risk fac tors were collected prior to surgery and those on menstrual cycle date s at the time of surgery, Logistic regression was used to assess risks (odds ratios [ORs]), Results: The crude OR for breast cancer in women with estrogen receptor-positive breast epithelium versus those withou t was 3.16 (95% confidence interval [CI] = 1.89-5.28), with an OR of 2 .49 (95% CI = 1.25-4.96) for premenopausal and an OR of 3.32 (95% CI = 1.43-7.68) for postmenopausal women, The ORs remained high and statis tically significant after controlling for age and other breast cancer risk factors. The level of estrogen receptor expression was higher in patients with breast cancer than in control subjects and it was relate d to breast cancer risk in postmenopausal women (P trend <.005), Expre ssion declined as expected in premenopausal control subjects as the me nstrual cycle progressed but rose in breast cancer patients (P trend < .015). Conclusions: The overexpression of estrogen receptors in normal breast epithelium may augment estrogen sensitivity and hence the risk of breast cancer.