Immunohistochemical profiles of normal and tumor breast from BRCA1 carriers and matched sporadic controls: Clues for chemoprevention

Abstract

9686 Background: Alternatives to surgical prophylaxis are hardly needed in women with a hereditary risk of breast cancer. The aim of this study was to screen BRCA1-related and sporadic breast tumors and non-tumor distant breast tissues for alterations susceptible to be targets for chemoprevention. Methods: 25 breast samples of BRCA1 mutation carriers and carefully matched sporadic controls were selected from the tumor bank of our institution. Tumor samples were screened using a tissue array, and normal and intermediate tissues from the same individuals by standard immunohistochemistry (IHC). Results: Both groups were comparable regarding the matching criteria: age (med 39 and 41), tumor size (med 23 and 22 mm), SBR grade (grade 3: 76 and 71%), histological type. In tumors, p53 over expression and high Ki67 expression rates did not differ between both groups, while PR (12 vs 38%, p=0.03) and, to a lesser extent, ER (p=0.08) were less often expressed in BRCA1-related tissues than in controls. In normal tissues, ER was significantly more often expressed (78 vs 45%, p=0.02) and Cox 2 over expression tended to occur more frequently in BRCA1-related samples (48%) than in controls (23%, p=0.07). Cox2 expression tended to be correlated with ER and PR negativity in BRCA1-related and control breast tumors, and the opposite in normal breast samples. Her2 and EGF-R expression did not differ significantly between both groups. 17% of normal BRCA1-related but none of the control normal breast tissues over expressed p53. Proliferative benign breast lesions were rare, as many in both groups. ER and Cox2 were expressed in most benign lesions in BRCA1 carriers as well as controls. Conclusions: Both the tumor and normal breast IHC profiles differ between BRCA1 mutation carriers and sporadic patients. The loss of ER expression is not an early event in BRCA1-related breast carcinogenesis. Cox2 is over expressed early in BRCA1 tissues independently of ER and PR expression, and may be a target for chemoprevention in this population. No significant financial relationships to disclose.