Clinical relevance of telomerase polymorphism for breast cancer: A systematic review.

PURPOSE: To perform a systematic review to explore the clinical relevance of hTERT polymorphisms for breast cancer (BC). METHODS: Twenty-nine polymorphic regions were evaluated after comprehensive searching of 1236 articles, and selection of 9 publications (total of 12986 cases and 16758 controls). RESULTS: About the influence of hTERT variants in BC risk, 3 studies showed that the variant rs2736098 was associated with increasing risk. The variants rs10069690 and rs2853676 were also described as risk factors for BC. Only one variant rs2736100 presented as risk factor for BC. MNS16A genotype influenced the risk of BC in an Iranian, but not in the Greek and American populations. The associations of 5 hTERT variants with expression of hormone receptors were also evaluated in some studies. One study showed that the variant rs10069690 was associated to the estrogen receptor (ER)-negative and triple negative subtype, but other authors did not find the same results. In addition, the association of rs273618 with ER-/progesterone receptor (PR)+ cases, and rs10069690, rs2735940, rs4246742 and rs2736100 with both negative receptors were described. After data reanalyses, we found that the variant rs2735940 and rs2736100 were associated with ER-/PR- cases among patients with BC. Also, the variant rs2736100 was associated with ER+/PR+ cases and the variant rs2736118 was associated to ER+/PR+ and ER-/PR+ cases. CONCLUSIONS: The associations between hTERT variants and BC risk and outcomes could be useful since a polymorphism can be identified before the diagnosis, but the heterogeneity of data and analyses found in different studies lead to many controversies.

A neoadjuvant, randomized, open-label phase II trial of afatinib versus trastuzumab versus lapatinib in patients with locally advanced HER2-positive breast cancer.

BACKGROUND: Chemotherapy is standard neoadjuvant treatment of LA BC. Patients with HER2-positive BC require targeted therapy. Trastuzumab and pertuzumab, which target HER2, with chemotherapy are approved as neoadjuvant therapy, however, treatments with different mechanisms of action might provide a broader range of activity. In this study we evaluated the efficacy and safety of the irreversible ErbB family blocker afatinib, versus trastuzumab or lapatinib in the neoadjuvant treatment of HER2-positive, LA BC. PATIENTS AND METHODS: Treatment-naive, HER2-positive BC patients with stage IIIA, B, C or inflammatory disease were randomized 1:1:1 to daily afatinib (50 mg), lapatinib (1500 mg), or weekly trastuzumab (4 mg/kg loading dose, then 2 mg/kg/wk) for 6 weeks until surgery or follow-up neoadjuvant treatment. The primary end point was objective response rate according to Response Evaluation Criteria in Solid Tumors (version 1.0). RESULTS: Recruitment was stopped early because of slow patient enrollment; 29 patients were randomized to afatinib (n = 10), lapatinib (n = 8), or trastuzumab (n = 11). Objective response was seen in 8 afatinib-, 6 lapatinib-, and 4 trastuzumab-treated patients. Eleven patients had stable disease (best response); 1 lapatinib- and 1 trastuzumab-treated patient had progressive disease. All 10 afatinib-treated patients experienced drug-related adverse events (commonly diarrhea, dermatitis acneiform, and paronychia) versus 6 of 8 lapatinib- (diarrhea and rash) and 5 of 11 trastuzumab-treated patients (vomiting and arthralgia). CONCLUSION: Afatinib demonstrated clinical activity that compared favorably to trastuzumab and lapatinib for neoadjuvant treatment of HER2-positive BC, with a safety profile consistent with epidermal growth factor receptor tyrosine kinase inhibitors.