TUMOR BIOLOGICAL FEATURES OF BRCA1-INDUCED BREAST AND OVARIAN-CANCER

BRCA1 mutations, although implicated in disease predisposition in a ma jor part of the hereditary breast cancer population, do nea, seem to b e crucially involved in tumorigenesis of sporadic breast and oval-lan cancers. This suggests that tumours arising in BRCA1 mutation carriers may differ from BRCA1 negative hereditary and sporadic cancer in gene tic and biological features, as well as in clinical behaviour, Prior t o BRCA1 analysis, 79 breast and 19 ovarian tumours from 57 breast and breast-ovarian cancer families, and 170 tumours from a comparison grou p of stage II breast cancers were studied with regard to histopatholog ical features; immunohistochemistry [c-erbB-2, p53, oestrogen receptor (ER) and progesterone receptor (PR)], DNA flow cytometry and S-phase fraction. BRCA1 mutations were found in 40 breast and 15 ovarian tumou rs. The BRCA1 positive breast tumours were significantly more often of ductal type, histological grade III and manifested a heavy lymphocyte infiltration. Additionally, as compared to BRCA1 negative tumours, th e BRCA1 positive tumours were significantly more often ER, PgR and c-e rbB-2 negative, Furthermore, they were significantly more often DNA no n-diploid, as well as being characterised by higher S-phase fraction v alues. These results suggest that BRCA1-induced breast cancers may man ifest distinct tumour biological features of clinical importance. (C) 1997 Published by Elsevier Science Ltd.