PATHOBIOLOGIC CHARACTERISTICS OF HEREDITARY BREAST-CANCER

Patients with hereditary breast cancer (HBC) present at a young age wi th breast cancers that show adverse pathological characteristics such as high nuclear grade, negative hormone receptor status, and high prol iferation indices. Surprisingly, the clinical course has been reported to be comparable or improved compared with patients with nonhereditar y breast cancer (non-HBC). To determine whether there are any molecula r markers that might help explain this paradox between pathologically aggressive neoplasms in patients with HBC and the lack of extreme clin ically aggressive disease, we studied several molecular parameters in a group of 34 breast cancer patients with mutations in either the BRCA 1 or BRCA2 tumor suppressor genes and compared them with a group of 20 breast cancer patients with non-HBC. In general, patients with HBC ha d tumors that were of higher nuclear grade, contained a higher populat ion of proliferating cells, showed increased expression of DNA topoiso merase II-alpha (topo II-alpha), lacked hormone receptors, and were mo re likely to show immunopositivity for the p53 tumor suppressor gene, Additionally, tumors from patients with HBC showed a decreased angioge nesis compared with controls. The decreased angiogenesis and the eleva ted expression of tops II-alpha (an anticancer drug target) may, in pa rt, explain the lack of correlation between clinical course and histol ogical characteristics in patients with HBC. Copyright (C) 1998 by W.B . Saunders Company.