TERT promoter hotspot mutations in breast cancer

BACKGROUND: Telomerase reverse transcriptase (TERT) promoter mutations have been discovered in solid and hematological malignancies, where they reflect TERT activation and cell-cycle progression. In melanoma, glioma, and thyroid cancers, TERT promoter mutations are associated with a poor prognosis. However, no studies have evaluated the prevalence and prognostic significance of TERT promoter mutations in breast cancer. METHODS: We analyzed TERT promoter hotspot mutations (C228T and C250T) using direct sequencing of DNA from 319 tumor tissues. We also collected clinical data from cases that were positive for TERT promoter mutations. RESULTS: We detected TERT promoter mutations in three (0.9%) of the 319 cases. Two patients had hormone receptor-positive and human epidermal growth factor receptor 2-negative cancer, while the third patient had triple-negative cancer. All three patients had initially been diagnosed with operable breast cancer and undergone surgical treatment. The relapse-free survivals of these patients were 83, 226, and 270 months, respectively. The mutations were C250T in the triple-negative cancer case and C228T in the remaining two cases. CONCLUSION: Given the rarity of TERT promoter mutations, further studies are needed to confirm their prognostic significance in breast cancer cases.