ER? expression and breast cancer risk prediction for women with atypias.

ABSTRACT: Estrogen receptor (ER) ? is highly expressed in normal breast epithelium and a putative tumor suppressor. Atypical hyperplasia substantially increases breast cancer risk, but identification of biomarkers to further improve risk stratification is needed. We evaluated ER? expression in breast tissues from women with atypical hyperplasia and association with subsequent breast cancer risk. ER? expression was examined by immunohistochemistry in a well-characterized 171-women cohort with atypical hyperplasia diagnosed 1967-1991. Nuclear ER? percent and intensity was scored in the atypia and adjacent normal lobules. An ER? sum score (percent + intensity) was calculated and grouped as low, moderate, or high. Competing risks regression was used to assess associations of ER? expression with breast cancer risk. After 15-year median follow-up, 36 women developed breast cancer. ER? expression was lower in atypia lobules in than normal lobules, by percent staining and intensity (both P < 0.001). Higher ER? expression in the atypia or normal lobules, evaluated by percent staining, intensity or sum score, decreased the risk of subsequent breast cancer by 2-fold (P = 0.04) and 2.5-fold (P = 0.006). High normal lobule ER? expression conferred the strongest protective effect in premenopausal women: the 20-year cumulative incidence of breast cancer was 0% for women younger than 45 years with high versus 31% for low-moderate ER? expression (P = 0.0008). High ER? expression was associated with a significantly decreased risk of breast cancer in women with atypical hyperplasia. These data suggest that ER? may be a useful biomarker for risk stratification and a novel therapeutic target for breast cancer risk reduction.

SUBMITTER: Hieken TJ 

PROVIDER: S-EPMC4633335 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature