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BRAF mutation in serous ovarian cancers associated with improved prognosis
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Thirty-five percent of patients with serous borderline or low-grade serous ovarian cancers had BRAF V600E mutations, according to study results.
Ten percent of serous ovarian cancers are low-grade chemoresistant disease, according to researchers. Previous studies have indicated that 28% to 35% of serous borderline or low-grade serous tumors have a BRAF mutation and may be susceptible to BRAF-inhibiting therapies.
Researchers conducted the current study to investigate whether BRAF or KRAS mutation status was associated with disease stage and/or histology in 75 patients with low-grade serous or serous borderline disease.
Fifty-six of the 75 tumors had serous borderline histology, and 19 had low-grade serous histology. Researchers observed KRAS mutation in 17 tumors, and they observed a BRAF V600E mutation in 26 tumors.
The investigators reported a significant link between BRAF V600E mutation and early-stage disease (stage I/II; P<.001). This mutation also was significantly associated with serous borderline histology (P=.002).
The researchers observed no significant associations between KRAS mutation and disease stage or histology.
Twenty-two patients required chemotherapy. Of those patients, 20 had tumors with wild-type KRAS/BRAF, two had KRAS mutations and none had tumors with BRAF mutation.
At a median follow-up of 3.6 years (range, 1.9-129.3 months), all patients with BRAF mutations were still alive.
“Patients with [serous borderline/low-grade serous] ovarian cancer who require systemic therapy are unlikely to have BRAF mutant tumors,” the researchers concluded.
“The article by Grisham et al shows us that, also contrary to the genetic progression usually seen in solid tumors, there is loss rather than gain of the BRAF or KRAS mutation,” Elise C. Kohn, MD, of the molecular signaling section in the medical oncology branch at the Center for Cancer Research at the NCI, and Jean Hurteau, MD, of the University of Chicago Pritzker School of Medicine, wrote in an accompanying editorial. “The highest frequency of mutation is in the borderline tumors, with mutational loss with progression to micro-papillary tumor and low-grade serous carcinoma.”
The results also indicate that low-grade serous disease with BRAF mutations did not recur.
“This is the antithesis of what we expect with these oncogenic mutations,” Kohn and Hurteau wrote.
The current study is an important contribution to the understanding of type 1 ovarian cancers, according to Kohn and Hurteau.
“These findings are important in that they can lead to triage decisions to reduce overtreatment of those women whose cancers are unlikely to occur,” they wrote.
For more information:
Grisham RN. Cancer. 2012;doi:10.1002/cncr.27782.
Kohn EC. Cancer. 2012;doi:10.1002/cncr.27833.
Disclosure: Kohn and Hurteau report no relevant financial disclosures.