Integridade e amplificação do gene HER2 na biópsia líquida no câncer de mama

Abstract

Introduction: Breast cancer is probably the most feared among women, because of its high incidence and its psychological effects, which affect sexuality and personal image. It is considered serious public health problem worldwide, with approximately 2.1 million new cases and 627.000 deaths from the disease each year. Objective: To evaluate the integrity and quantification of the human epidermal growth factor 2 (HER2) receptor gene amplification in plasma free cell circulating DNA (cfDNA) in luminal breast cancers. Methodology: Plasma was collected for cfDNA analysis during core-biopsy (cancer diagnosis). Tumor size was obtained from ultrasound and mammography and immunohistochemistry was performed from core-biopsy samples. CfDNA levels of the Alu sequence, (Alu sequences can be considered genomic instability factors), and HER2 amplification levels were quantified by qPCR gene expression analysis. Results Paper 1: 19 patients and 14 controls were analyzed. Total and long (apoptosis) and short (necrosis) cfDNA amounts were significantly higher in patients than in controls, except for cfDNA integrity (ratio of long and short segments). There was a correlation between tumor size and the amount of long and short Alu fragments, as well as cfDNA integrity. No differences in Alu cfDNA levels were observed when compared to molecular subtypes. Results Paper 2: We analyzed 33 patients, 22 HER2- and 11 HER2 +,according to the mmunohistochemistry evaluated at the time of diagnosis. Tumor size had a positive correlation with cfDNA level, and this event was significant. HER2 amplification level in cfDNA was not associated with histological type or histological grade of tumors. An increase in HER2 amplification was observed in patients positive for immunohistochemical diagnosis of HER2 (p = 0.004). The ROC curve was significant (AUC = 0.76, p = 0.016). Discussion: The results indicate that cfDNA Alu quantification differentiates patients and controls, however, may not be useful in differentiating early diagnosis of breast cancer. Future studies using cfDNA are suggested in advanced cancer. Analysis of HER2 amplification in cfDNA appears to have potential for clinical use as it could prevent HER2 + tumors from being underdiagnosed by immunohistochemistry, probably due to histological heterogeneity, as well as to reveal other metastatic sites where HER2 amplification may occur.