BRAF V600E confers male sex disease-specific mortality risk in patients with papillary thyroid cancer

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

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)2787-2795
Number of pages9
JournalJournal of Clinical Oncology
Volume36
Issue number27
DOIs
StatePublished - Sep 20 2018

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Wang, F., Zhao, S., Shen, X., Zhu, G., Liu, R., Viola, D., Elisei, R., Puxeddu, E., Fugazzola, L., Colombo, C., Jarzab, B., Czarniecka, A., Lam, A. K., Mian, C., Vianello, F., Yip, L., Riesco-Eizaguirre, G., Santisteban, P., O’Neill, C. J., ... Xing, M. M. (2018). BRAF V600E confers male sex disease-specific mortality risk in patients with papillary thyroid cancer. Journal of Clinical Oncology, 36(27), 2787-2795. https://doi.org/10.1200/JCO.2018.78.5097