Clinicopathologic Features of BRCA-Linked and Sporadic Ovarian Cancer
ABSTraCT & COmmentary
Synopsis: Advanced stage hereditary ovarian cancer patients survive longer than nonhereditary cancer patients.
Source: Boyd J, et al. JAMA 2000;283:2260-2265.
Boyd and colleagues conducted a retrospective cohort study of a consecutive series of 933 ovarian cancer patients diagnosed and treated at their institution over a 12-year period from 1986 through 1998. The purpose of their study was to determine whether hereditary ovarian cancers have distinct clinical and pathological features compared with sporadic (nonhereditary) ovarian cancers. The study was restricted to patients of Jewish origin because of the ease of BRCA1 and BRCA2 genotyping in this ethnic group. From the 189 patients who identified themselves as Jewish, 88 hereditary cases were identified with the presence of a germline founder mutation in BRCA1 or BRCA2. The remaining 101 cases from the same series not associated with a BRCA mutation and two additional groups (Gynecologic Oncology Group protocols 52 and 111) with ovarian cancer from clinical trials (for the survival analysis) were included for comparison. Outcome measures included age at diagnosis, surgical stage, histologic cell type and grade, surgical outcome, response to chemotherapy, and survival for advanced stage cases. 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. 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 (P < 0.001). Those with hereditary cancers had improved survival compared with the nonhereditary group (P = 0.004). For stage III cancers, BRCA mutation status was an independent prognostic factor (P = 0.03). Boyd et al concluded that, although BRCA-associated hereditary ovarian cancers in this population have surgical and pathological characteristics similar to those of sporadic cancers, advanced-stage hereditary cancer patients survive longer than nonhereditary cancer patients. Furthermore, age penetrance was greater for BRCA1-linked than for BRCA2-linked cancers in this population.
Comment by David M. Gershenson, MD
Based on the current state of knowledge, approximately 10% of epithelial ovarian cancers are hereditary. There exists a controversy concerning the influence of BRCA mutational status on outcome. Some studies have revealed a better prognosis for women with hereditary ovarian cancer compared with those with sporadic ovarian cancer, while other studies have shown no difference in outcome. The major strengths of this study are the size of the study population, the fact that all patients were treated in a single institution, and homogeneity of the study population (all were Jewish). The reason for the conflicting findings in various studies remains a mystery. Boyd et al suggest that the reason may lie in the fact that the studies not showing a difference in survival did not stratify for stage of disease; this explanation, however, is only hypothetical. Breast cancer studies have shown no consistent difference in survival between women with hereditary cancers and those with sporadic breast cancers. Although Boyd et al did demonstrate a statistically significant difference in median time to recurrence between the hereditary and sporadic ovarian cancer patients—14 vs. seven months—I am somewhat bothered by the fact that the median time to recurrence was so brief in the latter group. Most clinical trials have shown median progression-free survival times in the 13-18 month range for patients with advanced stage ovarian cancer. Although this is an excellent study, the controversy continues.
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