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  • Title: Steroid receptors in hereditary breast carcinomas associated with BRCA1 or BRCA2 mutations or unknown susceptibility genes.
    Author: Loman N, Johannsson O, Bendahl PO, Borg A, Fernö M, Olsson H.
    Journal: Cancer; 1998 Jul 15; 83(2):310-9. PubMed ID: 9669814.
    Abstract:
    BACKGROUND: The expression of steroid receptors is a common feature of both male and female breast carcinomas and is also one of the most important prognostic factors for patients with this disease. Steroid receptor levels in BRCA1-related breast carcinoma have reportedly been low. Little data on steroid receptor levels have been reported with regard to BRCA2. METHODS: Steroid receptor levels were analyzed in 27 breast carcinomas associated with BRCA1 mutations, 14 associated with BRCA2 mutations, and 32 from individuals who had hereditary breast carcinoma but no detectable mutations of either BRCA1 or BRCA2. Breast carcinomas from 32 consecutive male patients, 6 of whom had mutations of BRCA2, were also examined for steroid receptors. Estrogen receptor (ER) and progesterone receptor (PgR) analyses were performed with radioligand or enzyme immunoassay techniques on tumor cytosol preparations. Germline 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 tumors expressed significantly lower levels of ER than tumors from the other hereditary groups. The PgR levels were significantly lower in the BRCA1-related cases than in the hereditary cases not related to BRCA1 or BRCA2, but not significantly lower than in the BRCA2-related cases. Fourteen of 32 (44%) of the hereditary tumors not related to BRCA1 or BRCA2 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: BRCA1- and BRCA2-related breast tumors were distinct in their expression of steroid receptors. Moreover, a subgroup of tumors not related to BRCA1 or BRCA2 manifested a strongly positive PgR phenotype rarely seen in BRCA1- and BRCA2-related tumors. These characteristics may be of relevance to the treatment and follow-up of high risk individuals in these families and may help identify a homogeneous category of hereditary breast carcinomas not related to BRCA1 or BRCA2 in which new susceptibility genes may be sought.
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