Nuclear and Cytoplasmic hTERT, Tumor-Infiltrating Lymphocytes, and Telomere Elongation Leukocytes Are Independent Factors in the Response to Neoadjuvant Treatment in HER2-Enriched Breast Cancer

核和细胞质 hTERT、肿瘤浸润淋巴细胞和端粒延长白细胞是 HER2 富集型乳腺癌新辅助治疗反应的独立因素

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作者:Lucas Delmonico, José Bines, Cristina Moreira do Nascimento, Priscila Valverde Fernandes, Isabel de Souza Barbosa, Gabriel Brito Ribeiro, Bruno Henrique Rala de Paula, Rafaele Tavares Silvestre, Maria Helena Faria Ornellas, Gilda Alves, Claudia Lage

Abstract

HER2-enriched tumors are responsible for 20% of breast tumors and have high rates of immune infiltrates in the tumor stroma that respond favorably to neoadjuvant chemotherapy. In the context of tumors, telomeres control cell death and prevent tumor cells from replicating discontinuously, leading to their immortalization. This study aimed to evaluate the presence of tumor-infiltrating lymphocytes, hTERT expression, hTERT promoter mutation, and leukocyte telomere length in HER2-enriched breast tumors. A total of 103 cases were evaluated, 19 with pathologic complete response. The TILs percentage was above ≥10 in 44 cases (43%) and significantly present in patients ≥50 years of age. hTERT staining positivity was mostly nuclear, significantly present in the non-pCR group, and associated with a lower survival rate. Leukocyte telomeres were elongated for HER2-enriched tumors, and in multivariate analysis, shortening was associated with an increased risk of death. Overall, our results show that the nuclear and cytoplasmic presence of hTERT may indicate a worse prognosis and that leukocyte telomere elongation is a protective factor.

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