Association Between BRAF V600E Mutation and Recurrence of Papillary Thyroid Cancer

• DOI: 10.1200/jco.2014.56.8253
• Publication Date: 2014-10-21T04:15:31Z
• Authors: Mingzhao Xing; Ali S. Alzahrani; Kathryn A. Carson; Young Kee Shong; Tae Yong Kim; David Viola; Rossella Elisei; Bela Bendlová; Linwah Yip; Caterina Mian; Federica Vianello; R. Michael Tuttle; Eyal Robenshtok; James A. Fagin; Efisio Puxeddu; Laura Fugazzola; Agnieszka Czarniecka; Barbara Jarzab; Christine J. O'Neill; Mark S. Sywak; Alfred K. Lam; Garcilaso Riesco-...; Pilar Santisteban; Hirotaka Nakayama; Roderick Clifton-...; Giovanni Tallini; Elizabeth H. Holt; Vlasta Sýkorová
• Keywords: Adult; Male; Proto-Oncogene Proteins B-raf; Adult; Carcinoma, Papillary; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Proto-Oncogene Proteins B-raf; Retrospective Studies; Risk Assessment; Risk Factors; Thyroid Neoplasms; Mutation, Missense; Oncology and carcinogenesis not elsewhere classified; Mutation, Missense; Clinical sciences; Kaplan-Meier Estimate; Risk Assessment; 03 medical and health sciences; 0302 clinical medicine; Risk Factors; Humans; Adult; Carcinoma, Papillary; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Proto-Oncogene Proteins B-raf; Retrospective Studies; Risk Assessment; Risk Factors; Thyroid Neoplasms; Mutation, Missense; Cancer Research; Oncology; Thyroid Neoplasms; Retrospective Studies; Oncology and carcinogenesis; Middle Aged; Prognosis; Carcinoma, Papillary; 3. Good health; Female; Neoplasm Recurrence, Local; Follow-Up Studies

Purpose To investigate the prognostic value of BRAF V600E mutation for the recurrence of papillary thyroid cancer (PTC). Patients and Methods This was a retrospective multicenter study of the relationship between BRAF V600E mutation and recurrence of PTC in 2,099 patients (1,615 women and 484 men), with a median age of 45 years (interquartile range [IQR], 34 to 58 years) and a median follow-up time of 36 months (IQR, 14 to 75 months). Results The overall BRAF V600E mutation prevalence was 48.5% (1,017 of 2,099). PTC recurrence occurred in 20.9% (213 of 1,017) of BRAF V600E mutation–positive and 11.6% (125 of 1,082) of BRAF V600E mutation–negative patients. Recurrence rates were 47.71 (95% CI, 41.72 to 54.57) versus 26.03 (95% CI, 21.85 to 31.02) per 1,000 person-years in BRAF mutation–positive versus –negative patients (P < .001), with a hazard ratio (HR) of 1.82 (95% CI, 1.46 to 2.28), which remained significant in a multivariable model adjusting for patient sex and age at diagnosis, medical center, and various conventional pathologic factors. Significant association between BRAF mutation and PTC recurrence was also found in patients with conventionally low-risk disease stage I or II and micro-PTC and within various subtypes of PTC. For example, in BRAF mutation–positive versus –negative follicular-variant PTC, recurrence occurred in 21.3% (19 of 89) and 7.0% (24 of 342) of patients, respectively, with recurrence rates of 53.84 (95% CI, 34.34 to 84.40) versus 19.47 (95% CI, 13.05 to 29.04) per 1,000 person-years (P < .001) and an HR of 3.20 (95% CI, 1.46 to 7.02) after adjustment for clinicopathologic factors. BRAF mutation was associated with poorer recurrence-free probability in Kaplan-Meier survival analyses in various clinicopathologic categories. Conclusion This large multicenter study demonstrates an independent prognostic value of BRAF V600E mutation for PTC recurrence in various clinicopathologic categories.