BRCA DEFICIENT OVARIAN CANCER OFTEN SPREADS TO VISCERA

NEW YORK (Reuters Health) Apr 22 - Women with sporadic ovarian cancer and BRCA1/2 germline mutations have a higher risk for visceral metastases, researchers from Scotland suggested in the Journal of Clinical Oncology. Their report appeared online April 19.

The authors say that to their knowledge, "no association between BRCA1/2 mutation status and frequency of visceral relapse has been reported previously in ovarian cancer."

The clinical implications of these findings are twofold, according to lead author Dr. Charlie Gourley from University of Edinburgh and colleagues. First, the researchers advise clinicians to consider BRCA1/2 mutations in women with ovarian cancer who develop visceral metastases. This might inform genetic counseling for both the patient and her family, and it might also identify women who are eligible for trials of the poly ADP-ribose polymerase (PARP) inhibitor olaparib, they say.

"Second, our data extend the BRCAness phenotype in ovarian cancer. It suggests that BRCA1/2-associated ovarian cancer is a discrete clinical entity, the behavior of which is different from most sporadic ovarian cancers," the investigators said.

Dr. Gourley and his associates compared the rates of visceral relapse in women with BRCA1/2-deficient epithelial ovarian cancer/primary peritoneal cancer (EOC/PPC) to those in women with nonhereditary EOC/PPC.

They identified all 79 patients with EOC/PPC and BRCA1/2 germline mutations diagnosed in Scotland before May 2008. Fifteen of the women had inadequate clinical data, 2 had carcinosarcoma, 27 had previous breast cancer, and 16 were in remission; all were excluded.

Of the remaining 19 patients with BRCA1/2 mutations, 14 (74%) developed visceral metastases, compared to 6 (16%) of 38 matched control patients.

The rates of liver, lung and splenic metastases in the BRCA1/2 mutation carriers were 53%, 32%, and 32%, respectively, compared to 5%, 3%, and 5%, respectively, in controls.

Compared with controls with no personal or family history of BRCA1/2-associated malignancies, study subjects with no breast cancer history who relapsed from EOC/PPC had a 21-fold higher rate of visceral metastases.

"This relationship is particularly strong for BRCA1 mutation carriers, 92% of whom developed visceral metastases compared with only 16% in our control group," the research team reported.

The overall median follow-up for patients who remained alive without visceral metastases was 30 months (range, 8 to 104). After excluding events that occurred outside of the matched follow-up period, the frequency of all visceral, hepatic, pulmonary, and splenic metastases in BRCA1/2 mutation carriers was 58%, 42%, 16%, and 32%, respectively. All of these were significantly greater than in matched controls (range, 0% to 5%).

The researchers repeated the analysis using an independent validation set of 24 patients with BRCA1/2-deficient ovarian cancer treated in a phase I study of olaparib plus two matched controls for each patient. In this analysis, the frequency of visceral, hepatic, pulmonary and splenic metastases was similar to that in the initial data set (63%, 46%, 13%, and 17%, respectively). Again, the rates were higher than in matched controls (11%, 4%, 2% and 2%, respectively), although only the differences in total visceral and hepatic metastases reached statistical significance, the authors say.

As theirs was a retrospective study, Dr. Gourley and colleagues point out that additional studies will be required to confirm their findings.

J Clin Oncol 2010.