Age-Associated Mortality Risk and BRAF V600E Status in Papillary Thyroid Cancer


Key Points

  • Age-associated mortality risk was observed in patients with BRAF V600E mutation.
  • No significant age-associated mortality risk was observed in patients with wild-type BRAF.

In a study reported in the Journal of Clinical Oncology, Shen et al found evidence that BRAF V600E mutation status explains the long-recognized increased mortality risk associated with age at diagnosis in patients with papillary thyroid cancer.

Study Details

The study involved data from 2,638 patients (623 men and 2,015 women) from 11 medical centers in 6 countries. Patients had a median age of 46 years at diagnosis (interquartile range = 35–58 years) and median follow-up of 58 months (interquartile range = 26–107 months).  A total of 1,094 patients (41%) had BRAF V600E mutation.

Median age was 48 years among patients with BRAF V600E mutation and 44 years among those with wild-type BRAF. Women accounted for 75% and 77% of the two groups.  

Age-Associated Risk

A linear association between patient age and mortality was observed among patients with BRAF V600E mutation but not in those with wild-type BRAF, with the mortality rate remaining low and flat with increasing age in the latter group. The correlation between age and mortality rate was strongly positive in BRAF V600E patients (r = 0.94, P = .002) but not in wild-type BRAF patients (r = 0.41, P = .36). Kaplan-Meier survival curves rapidly declined with increasing age in the BRAF V600E mutation group but not in the wild-type BRAF group, even among patients aged > 75 years.

In analysis adjusting for clinicopathologic characteristics, hazard ratios for mortality for age 50 years, 60 years, 70 years, and 80 years vs age 45 years were 1.47, 4.03, 12.92, and 42.35 among patients with BRAF V600E mutation and 1.56, 1.92, 1.64, and 1.38 among BRAF wild-type patients. Similar results were observed when analysis was limited to patients with the conventional variant of papillary thyroid cancer.

The investigators concluded, “The long-observed age-associated mortality risk in [papillary thyroid cancer] is dependent on BRAF status; age is a strong, continuous, and independent mortality risk factor in patients with BRAF V600E mutation but not in patients with wild-type BRAF. These results question the conventional general use of patient age as a high-risk factor in [papillary thyroid cancer] and call for differentiation between patients with BRAF V600E and wild-type BRAF when applying age to risk stratification and management.”  

The study was supported by grants from the US National Institutes of Health, Polish National Center of Research and Development, Menzies Health Institute, Griffith University, Queensland Cancer Council and Queensland Smart State Fellowship, and others.

Michael Mingzhao Xing, MD, PhD, of The Johns Hopkins University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article. 

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