BRAF V600E Confers Male Sex Disease-Specific Mortality Risk in Patients With Papillary Thyroid Cancer

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Wang, Fei
Zhao, Shihua
Shen, Xiaopei
Zhu, Guangwu
Liu, Rengyun
Viola, David
Elisei, Rossella
Puxeddu, Efisio
Fugazzola, Laura
Colombo, Carla
Jarzab, Barbara
Czarniecka, Agnieszka
Lam, Alfred K
Mian, Caterina
Vianello, Federica
Yip, Linwah
Riesco-Eizaguirre, Garcilaso
Santisteban, Pilar
O'Neill, Christine J
Sywak, Mark S
Clifton-Bligh, Roderick
Bendlova, Bela
Sykorova, Vlasta
Wang, Yangang
Xing, Mingzhao
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2018
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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 wild-type 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 in-significant 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.

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JOURNAL OF CLINICAL ONCOLOGY

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36

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27

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© 2018 American Society of Clinical Oncology. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.

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Clinical sciences

Oncology and carcinogenesis

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