BRAF V600E Mutation Predicts Recurrence of Papillary Thyroid Cancer
In a large retrospective study reported in the Journal of Clinical Oncology, Xing et al found that presence of the BRAF V600E mutation was an independent predictor of recurrence of papillary thyroid cancer.
The study involved 2,099 patients with papillary thyroid cancer consecutively selected over different time periods between 1978 and 2011 at 16 medical centers in 8 countries. Among the 2,099 patients, 1,615 were women and 484 were men and median age was 45 years (interquartile range = 34–58 years).
Increased Risk
BRAF V600E mutation was present in 1,017 patients (48.5%). Over median follow-up of 36 months (interquartile range = 14–75 months), recurrence was observed in 20.9% of mutation-positive patients vs 11.6% of mutation-negative patients. Recurrence rates were 47.71 (95% confidence interval [CI] = 41.72-54.57) vs 26.03 (95% CI = 21.85-31.02) per 1,000 person-years, yielding a hazard ratio (HR) of 1.82 (P < .001).
The hazard ratio remained significant in multivariate analyses adjusting for patient age and sex and stratification by medical center (HR = 1.63, 95% CI = 1.29–2.06) and after additional adjustment for tumor size, extrathyroidal invasion, lymph node metastasis, multifocality, and papillary thyroid cancer subtype (HR = 1.38, 95% CI = 1.07–1.80).
Conventional and Follicular-Variant Papillary Thyroid Cancer
The BRAF mutation was significantly associated with recurrence both among patients with common conventional papillary thyroid cancer and among those with follicular-variant papillary thyroid cancer. In those with conventional papillary thyroid cancer, mutation prevalence was 56.1%, recurrence was observed in 20.7% of mutation-positive patients (168/813) vs 12.4% of mutation-negative patients (79/635), and recurrence rates were 44.92 vs 25.63 per 1,000 person-years (HR = 1.75, 95% CI = 1.34–2.29); hazard ratios remained significant on multivariate analyses (1.48, 95% CI = 1.11–1.96; 1.46, 95% CI = 1.08–1.99).
In patients with follicular-variant papillary thyroid cancer, mutation prevalence was 20.6%, recurrence was observed in 21.3% of mutation-positive patients (19/89) vs 7.0% of mutation-negative patients (24/342), and recurrence rates were 53.84 vs 19.47 per 1,000 person-years (HR = 3.20, P < .001); hazard ratios remained significant on multivariate analyses (HR = 4.02, 95% CI = 1.95–8.28; HR = 3.20, 95% CI = 1.46–7.02).
Recurrence-Free Survival
Kaplan-Meier analysis showed that the presence of the BRAF V600E mutation was associated with significantly poorer recurrence-free survival in all patients, those with conventional papillary thyroid cancer, and those with follicular-variant papillary thyroid cancer (all P < .001). Compared with patients without the mutation and without lymph node metastases, extrathyroidal extension, or age < 60 years, recurrence-free survival was significantly reduced among patients with the mutation and without the clinicopathologic risk factor (ie, lymph node metastases, extrathyroidal extension, or age ≥ 60 years), among those without the mutation and with the clinicopathologic risk factor, and among those with both the mutation and the risk factor (P < .01 for all).
The investigators concluded: “This large multicenter study demonstrates an independent prognostic value of BRAFV600E mutation for [papillary thyroid cancer] recurrence in various clinicopathologic categories.”
Mingzhao Xing, MD, PhD, of Johns Hopkins University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by grants from the National Institutes of Health and by many others. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
