Study Shows BRCA Mutation Screening Needed Despite Family History

A new Japanese study has revealed that about 13% of unselected women with ovarian cancer seen at a single center in Japan had BRCA1/2 mutations. The study, published in Cancer, also revealed no significant differences in the rate of BRCA mutations between patients with or without family histories of the mutations.

Researcher Ikuko Sakamoto, MD, of Yamanashi Prefectural Central Hospital, and colleagues pointed out that prior studies of BRCA1/2 mutations conducted in Asian countries, including Japan, have suggested “marked geographical differences in the positive rates of BRCA1/2 mutations,” with mutation rates in the 2% to 6% range compared with rates in the 11% to 17% range in Western countries.

“However, our study, which analyzed whole exons and exon-intron junctions of BRCA1/2 with a next generation sequencer, revealed that the frequency of BRCA1/2 mutations (13%) was comparable to rates reported from Western countries,” wrote Sakamoto and colleagues. “These discrepancies may be due to differences in the experimental protocols.”

The study enrolled 95 unselected women with ovarian cancer seen at Yamanashi Prefectural Central Hospital between 2013 to 2015. Using next generation sequencing, the researchers analyzed these patients for BRCA1/2 mutations.

They found that 12.6% of the patients had BRCA1/2 mutations; five patients (5.3%) had BRCA1 mutations and seven (7.4%) had BRCA2 mutations. Similar rates of mutations were found between women with a familial history (16.7%) and those without a history (10.2%).

“Because the frequency of BRCA1/2 mutations was unexpectedly high in the cases with no family history, we examined the number of family members from whom we were able to obtain family history,” the researchers wrote. “There was no difference in the mean number of family or in the number of female family members.”

The researchers also analyzed the presence of BRCA mutations and their clinical relevance. No difference in age or primary tumor site were found between patients positive for mutations and those negative for mutations. Patients with mutations were diagnosed at more advanced stages with 100% of BRCA-positive cases having stage III or stage IV disease. In addition, 100% of patients positive for mutations had high-grade serous adenocarcinomas.

Based on their results, the researchers recommended that “BRCA1/2 genetic testing be required for all ovarian cancer patients (mainly those with a serous histology and at advanced stages), regardless of family history, race, or age.”