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

• Published in: Current oncology (Toronto) 2023-04, Vol.30 (4), p.4094-4109
• Main Authors: Delmonico, Lucas, Bines, José, Nascimento, Cristina Moreira do, Fernandes, Priscila Valverde, Barbosa, Isabel de Souza, Ribeiro, Gabriel Brito, de Paula, Bruno Henrique Rala, Silvestre, Rafaele Tavares, Ornellas, Maria Helena Faria, Alves, Gilda, Lage, Claudia
• Format: Article
• Language: English
• Subjects: Adjuvant treatment; Analysis; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer; Cell death; Development and progression; Ethylenediaminetetraacetic acid; Female; HER2-enriched; hTERT; Humans; Lymphocytes; Lymphocytes, Tumor-Infiltrating - metabolism; Lymphocytes, Tumor-Infiltrating - pathology; Neoadjuvant Therapy - methods; pathological complete response; Pertuzumab; Prognosis; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; telomere length; Telomeres
• ISSN: 1718-7729; 1198-0052; 1718-7729
• DOI: 10.3390/curroncol30040311

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.