PerspectiveIn the Journals

BRAF V600E mutation increased recurrence risk in papillary thyroid cancer

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November 12, 2014

Presence of a BRAF V600E mutation appeared to predict recurrence in patients treated for papillary thyroid cancer, according to results of a retrospective, multicenter study.

Researchers evaluated 2,099 patients (1,615 women and 484 men) treated at one of 16 medical centers in eight countries. The mean age of patients was 45 years (interquartile range [IQR], 34-58).

All patients underwent total thyroidectomy, and therapeutic neck dissection was performed when appropriate. The researchers recorded information about patient demographics and papillary thyroid cancer (PTC) stage, and tissue from PTC tumors was sequenced to identify BRAF V600E mutations.

Median follow-up was 36 months (IQR, 14-75).

The researchers determined the overall prevalence of BRAF V600E mutations was 48.5% (n=1,017). PTC recurred in a higher percentage of patients with BRAF V600E mutation-positive patients than BRAF V600E mutation-negative patients (20.9% vs. 11.6%).

Researchers calculated a recurrence rate of 47.71 (95% CI, 41.72-54.58) per 1,000 person-years among patients with BRAF V600E mutations, compared with a recurrence rate of 26.03 (95% CI, 21.85-31.02) per 1,000 person-years among those without the mutation (HR=1.82; 95% CI, 1.46-2.28). The trend persisted in a multivariable model adjusted for patient age and gender, medical center, and various pathological characteristics.

Researchers also observed the correlation between BRAF V600E mutation and recurrence in patients whose PTC generally was considered low risk (stage I or II) and micro-PTC, as well as within various PTC subtypes.

“This was a large multicenter study that provided sufficient power to address the prognostic value of BRAF V600E mutation for the recurrence of PTC in various clinicopathologic categories,” the researchers wrote. “These results, together with the recent demonstration of the strong association of BRAF V600E mutation with PTC-associated patient mortality, help establish a prognostic value of BRAF V600E mutation in PTC.”

Disclosure:  See the full study for a list of the researchers’ relevant financial disclosures.

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PERSPECTIVE
Much of the progress we see in medicine arises from continued progress in better risk stratification. For diseases such as papillary thyroid cancer (PTC), this becomes of critical importance. PTC accounts for more than 80% of thyroid cancers and can be classified into several subtype variants, including classical PTC and follicular variant PTC. PTC is a highly curable disease. Thus, it is particularly important to distinguish the subset of patients who may benefit from more aggressive surveillance and/or therapy from those who will not.
In the article, Xing and colleagues conducted a retrospective global multicenter study of 2,099 patients with PTC to determine if BRAF V600E mutation was associated with increased PTC recurrence. It is worth highlighting that the same authors presented data last year showing that BRAF V600E was significantly associated with increased PTC-related mortality (Xing M. JAMA. 2013;309:1493-1501).
Not surprisingly, we see that BRAF V600E mutation status was associated with higher rates of PTC recurrence, which remained significant after adjustments for various clinicopathologic factors. Importantly, the large sample size allowed the authors to show that BRAF V600E is a poor prognostic marker in patients with conventionally low-risk disease (stage I or stage II) and micro-PTC, as well as within various subtypes of PTC.
Not withstanding the relatively short study follow-up (median 36 months), the collective evidence implicates BRAF V600E mutation as a prognostic factor in PTC, but it remains unclear how BRAF mutation status — alone and/or with others — can best be implemented in clinical practice. Well-designed prospective studies will be needed to address this.

Joanne Ngeow and Charis Eng, MD

Disclosure: Ngeow and Eng report no relevant financial disclosures.