STEROID-RECEPTORS IN HEREDITARY BREAST CARCINOMAS ASSOCIATED WITH BRCA1 OR BRCA2 MUTATIONS OR UNKNOWN SUSCEPTIBILITY GENES

BACKGROUND. The expression of steroid receptors is a common feature of both male and female breast carcinomas and is also one of the most im portant prognostic factors for patients with this disease. Steroid rec eptor levels in BRCA1-related breast carcinoma have reportedly been lo w. Little data on steroid receptor levels have been reported with rega rd to BRCA2. METHODS. Steroid receptor levels were analyzed in 27 brea st carcinomas associated with BRCA1 mutations, 14 associated with BRCA 2 mutations, and 32 from individuals who had hereditary breast carcino ma but no detectable mutations of either BRCA1 or BRCA2. Breast carcin omas from 32 consecutive male patients, 6 of whom had mutations of BRC A2, were also examined for steroid receptors. Estrogen receptor (ER) a nd progesterone receptor (PgR) analyses were performed with radioligan d or enzyme immunoassay techniques on tumor cytosol preparations. Germ line mutation screening and detection were performed using the protein truncation test, single strand conformation polymorphism, and direct sequencing on DNA from normal tissue. RESULTS. The BRCA1-related tumor s expressed significantly lower levels of ER than tumors from the othe r hereditary groups. The PgR levels were significantly lower in the BR CA1-related cases than in the hereditary cases not related to BRCA1 or BRCA2, but not significantly lower than in the BRCA2-related cases. F ourteen of 32 (44%) of the hereditary tumors not related to BRCA1 or B RCA2 had PgR levels exceeding 100 fmol/mg of protein. The tumors from male patients with BRCA2-related disease did not have receptor levels that differed from those in non-BRCA2-related tumors. CONCLUSIONS. BRC A1- and BRCA2-related breast tumors were distinct in their expression of steroid receptors. Moreover, a subgroup of tumors not related to BR CA1 or BRCA2 manifested a strongly positive PgR phenotype rarely seen in BRCA1- and BRCA2-related tumors. These characteristics may be of re levance to the treatment and follow-up of high risk individuals in the se families and may help identify a homogenous category of hereditary breast carcinomas not related to BRCA1 or BRCA2 in which new susceptib ility genes may be sought. (C) 1998 American Cancer Society.