Men with BRAF-mutated papillary thyroid cancer may have worse survival outcomes

Male sex appeared to be an independent risk factor for poor clinical outcomes among patients with BRAF V600E-mutated papillary thyroid cancer, according to results from a retrospective analysis.

“This study helps reconcile previous controversial findings on the role of male sex in the prognosis of papillary thyroid cancer and supports its use as an independent risk factor in clinical risk staging, particularly mortality risk, for patients with BRAF V600E papillary thyroid cancer,” Mingzhao Xing, MD, PhD, professor of medicine in the department of oncology and pathology at Johns Hopkins University School of Medicine and co-director of the Johns Hopkins Thyroid Tumor Center, and colleagues wrote. “In contrast, male sex is not an independent prognostic risk in patients with wild-type BRAF papillary thyroid cancer.”

Papillary thyroid cancer accounts for 85% to 90% of all thyroid malignancies and, although generally indolent, can be aggressive in some cases. Individualized patient treatment of optimal benefit-harm balance — based on appropriate risk stratification — is essential for management.

Male sex has remained a controversial risk factor for papillary thyroid cancer, demonstrating an adverse effect in some, but not all, studies.

Xing and colleagues sought to determine whether BRAF V600E — which is associated with aggressive tumor behavior and occurs among up to 45% of papillary thyroid cancers — might constitute a genetic background conferring male sex mortality risk and, thus, whether BRAF status could differentiate the prognostic risk of male sex.

The analysis included 2,638 patients (76.4% women; median age at diagnosis, 46 years) with papillary thyroid cancer enrolled at 11 medical centers in six countries who received treatment with total or near-total thyroidectomy and therapeutic neck dissection.

Genomic DNA had previously been isolated from primary papillary thyroid tumors and sequenced at exon 15 of the BRAF gene to identify BRAF V600E mutation, which researchers retrospectively examined to determine mutation status.

Median clinical follow-up time was 58 months (interquartile range, 26-107).

The overall prevalence of BRAF V600E mutation was 41.8% and did not differ between men (43.8%) and women (41.2%).

Incidence of distant metastasis did not differ between men and women with wild-type BRAF papillary thyroid cancer. However, among patients with BRAF V600E disease, significantly more men than women had distant metastasis, a risk factor for mortality (8.9% vs. 3.7%; P = .001).

Mortality rates were significantly higher among men vs. women with BRAF V600E disease (6.6% vs. 2.9%; HR = 2.43; 95% CI, 1.3-4.53), an association that persisted after clinicopathologic multivariable adjustment (HR = 2.74; 95% CI, 1.38-5.43).

However, among those with wild-type BRAF papillary thyroid cancer, the mortality rate was 1.4% among men compared with 0.9% among women (HR = 1.59; 95% CI, 0.55-4.57). Men did not demonstrate a significantly increased mortality risk after clinicopathologic multivariable adjustment (HR = 0.7; 95% CI, 0.23-2.09).

In conventional-variant papillary thyroid cancer, male sex had no impact on patients with wild-type BRAF disease. However, among those with BRAF V600E disease, mortality rates were 7.2% among men compared with 2.9% among women (HR = 2.86; 95% CI, 1.45-5.67). This remained significant after multivariable adjustment (HR = 3.51; 95% CI, 1.62-7.63).

“Our study provides another example that BRAF V600E is a genetic background underpinning the mortality risk of some classic clinical factors of papillary thyroid cancer,” researchers wrote. – by Melinda Stevens

Disclosures: Xing reports royalties as coholder of a licensed U.S. patent related to BRAF V600E mutation in thyroid cancer. Please see the study for all other authors’ relevant financial disclosures.