BRAF V600E mutations linked with increased mortality in thyroid cancer

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1. BRAF V600E mutations in patients with papillary thyroid cancer is associated with an increase in mortality.

2. Despite an association, BRAF V600E does not appear to add prognostic information after adjusting for clinical and histopathological features of the tumor.

Study Rundown: While this retrospective study observed a significant association between the BRAF V600E mutation and papillary thyroid cancer (PTC) associated mortality, statistical significance was not maintained after adjusting for clinical and histopathologic features of an aggressive tumor. The stipulated interaction between the mutation and clinicopathological factors suggests that the mutation may play a role in driving the molecular pathogenesis which leads to aggressive tumor behavior. Given that BRAF V600E testing does not seem to add more prognostic information for patients, it does not currently appear provide any utility in everyday clinical practice in the management of PTC.

Click to read the study in JAMA

Click to read an accompanying editorial in JAMA

In-Depth [retrospective, multicenter study]: This study collected patient data from 1,849 individuals with PTC treated and followed in 13 medical centers situated in 7 countries from 1978 to 2011. The overall prevalence of BRAF V600E mutation was 45.7% with an overall mortality of 3% (56/1849), 80.4% (45/56) of which were positive for BRAF V600E. Deaths per 1000 person-years was 12.87 vs. 2.52 in BRAF V600E vs. mutation negative patients with an HR of 2.66 (95% CI, 1.30-5.43). When aggressive features of the tumor (e.g. distant metastasis) were included for analysis, the association was no longer significant (HR 1.21; 95% CI, 0.53-2.76). It is notable that some of the clinicopathological factors (e.g. age, lymph node status) showed an additive interaction with the BRAF V600E mutation, significantly increasing mortality risk.

By Elizabeth Park and Rif Rahman

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