BRAF V600E Confers Male Sex Disease-Specific Mortality Risk in Patients With Papillary Thyroid Cancer.
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2020
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Journal of Clinical Oncology
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Abstract
Purpose
To test whether the prognostic risk of male sex in papillary thyroid cancer (PTC) is determined by
BRAF V600E and can thus be stratified by BRAF status.
Patients and Methods
We retrospectively investigated the relationship between male sex and clinicopathologic outcomes
in PTC, particularly mortality, with respect to BRAF status in 2,638 patients (male, n = 623; female, n =
2,015) from 11 centers in six countries, with median age of 46 years (interquartile range, 35-58 years)
at diagnosis and median follow-up time of 58 months (interquartile range, 26-107 months).
Results
Distant metastasis rates in men and women were not different in wild-type BRAF PTC but were
different in BRAF V600E PTC: 8.9% (24 of 270) and 3.7% (30 of 817; P = .001), respectively. In wildtype BRAF PTC, mortality rates were 1.4% (five of 349) versus 0.9% (11 of 1175) in men versus
women (P = .384), with a hazard ratio (HR) of 1.59 (95% CI, 0.55 to 4.57), which remained insignificant at 0.70 (95% CI, 0.23 to 2.09) after clinicopathologic multivariable adjustment. In BRAF
V600E PTC, mortality rates were 6.6% (18 of 272) versus 2.9% (24 of 822) in men versus women
(P = .006), with an HR of 2.43 (95% CI, 1.30 to 4.53), which remained significant at 2.74 (95% CI,
1.38 to 5.43) after multivariable adjustment. In conventional-variant PTC, male sex similarly had no
effect in wild-type BRAF patients; mortality rates in BRAF V600E patients were 7.2% (16 of 221)
versus 2.9% (19 of 662) in men versus women (P = .004), with an HR of 2.86 (95% CI, 1.45 to 5.67),
which remained significant at 3.51 (95% CI, 1.62 to 7.63) after multivariable adjustment.
Conclusion
Male sex is a robust independent risk factor for PTC-specific mortality in BRAF V600E patients but
not in wild-type BRAF patients. The prognostic risk of male sex in PTC can thus be stratified by BRAF
status in clinical application.