Study Shows Women With Hereditary 

Ovarian Cancer Have Longer Survival 

Than Women With Non-Hereditary Disease

Women with BRCA-associated hereditary ovarian cancer in the advanced stages have a longer survival compared with women with sporadic ovarian cancer, according to probability analyses in an article appearing in the May 3 issue of The Journal of the American Medical Association (JAMA).

Jeff Boyd, Ph.D., from Memorial Sloan-Kettering Cancer Center, New York, and colleagues studied patients with ovarian cancer to determine whether hereditary ovarian cancers have distinct clinical and pathological features compared with sporadic (nonhereditary) ovarian cancers. Jewish patients were studied because of the relative ease of BRCA1 and BRCA2 genotyping in this ethnic group, yielding 88 cases of BRCA-linked hereditary ovarian cancer and 101 cases without a BRCA mutation. For survival analysis, two additional groups from other clinical trials totaling 735 patients with stage III or IV ovarian carcinoma were used for comparison.

The hereditary and sporadic ovarian cancer groups were found to have similar disease characteristics. However, the researchers found that women with BRCA1-linked cancers were diagnosed at an earlier age than counterparts with BRCA2-linked cancer. "Hereditary cancers were rarely diagnosed before age 40 years and were common after age 60 years, with mean age at diagnosis being significantly younger for BRCA1 vs. BRCA2-linked patients (54 vs 62 years)," the researchers explain. "Histology, grade, stage and success of cytoreductive surgery were similar for hereditary and sporadic cases. The hereditary group had a longer disease-free interval following primary chemotherapy in comparison with the nonhereditary group, with a median time to recurrence of 14 months and seven months, respectively. Those with hereditary cancers had improved survival compared with the nonhereditary group. For stage III cancers, BRCA mutation status was an independent prognostic variable."

A 25 percent decrease in relative risk of death was reported for those with stage III hereditary ovarian cancer vs. those with sporadic cases after adjusting for age and extent of surgical cytoreduction.

According to background information in the article, about 10 percent of all epithelial (cells that line and cover the body's organs) ovarian carcinomas are associated with genetic predisposition, conferred primarily by inherited mutations in BRCA1 or BRCA2. The BRCA genes function as classic tumor suppressors, with loss of function of both alleles (any one of a series of two or more different genes that may occupy the same position on a chromosome) required for tumor growth. The authors note that past studies on the clinical features of hereditary ovarian cancer have produced inconsistent findings, especially regarding survival.

The researchers hypothesize: "If ovarian cancers associated with BRCA mutations are in fact more susceptible to therapeutic agents that induce a particular form of DNA damage, double-strand breaks for example, then this patient population may prove even more responsive to selected chemotherapeutic agents that induce that type of DNA damage."

Journal of the American Medical Association 2000;283:2260-2265) Courtesy of Doctor's Guide

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