Características clínico-patológicas e prognósticas do câncer de mama em mulheres na pré-menopausa e pesquisa da variante R337H no gene TP53 em um sub-grupo dessas pacientes : um estudo piloto

Abstract

Breast cancer is the most prevalent type of cancer in Brazil and worldwide, except for non-melanoma skin cancer. Studies demonstrate that patients diagnosed with breast cancer before the age of 50 have a worse prognosis when compared to those diagnosed after menopause. In Brazil, few studies investigating the clinical-pathological characteristics and patterns of survival stratified by age groups of premenopausal women with breast cancer were found in the literature. Furthermore, the presence of the R337H variant in the TP53 gene has also been associated with the development of early breast cancer in Brazil, however the frequency of this variant in the Central region of the country is not known. The aim of this study was to investigate the R337H variant in the TP53 gene in a group of premenopausal women with breast cancer and its possible associations with clinical, pathological and prognostic aspects. The research comprises a retrospective study of 206 patients with breast carcinomas diagnosed before the age of 50, between 2001 and 2013, selected from the records of the Laboratory of Immunohistochemistry of the Department of Pathological Anatomy, Hospital Araújo Jorge, in Goiânia (GO). For the detection of the R337H variant in the TP53 gene, the PCR-RFLP method using the restriction enzyme Hha I was performed. Pearson's chi-square was performed to verify significant differences between age groups. Kaplan-Maier and Long-Rank were performed to generate survival curves and to verify significant differences between them. The age of the patients at diagnosis ranged from 21 to 49 years and the mean age was 34 years (± 4.3). The five-year overall survival for the group was 61.8%. Younger patients, diagnosed before 32 years old, had a worse prognosis (52.3%) when compared to other age groups (p = 0.049). The younger patients also had a higher percentage of T4 tumors (33.3%) (p = 0.045) and advanced stage of the disease (III-IV) (79.1%) (p = 0.007). Among 36 samples of breast cancer diagnosed in premenopausal women, three had the R337H variant in the TP53 gene, corresponding to a frequency of 8.3%. We concluded that the clinicopathological and molecular (immunohistochemical) characteristics of patients diagnosed with breast cancer before the age of 50 years were associated with low overall survival. In addition, patients diagnosed before 32 years of age had more aggressive tumor characteristics and worse prognosis when compared to other age groups. Our results suggest that patients diagnosed with premenopausal breast cancer in the Central-Western region of Brazil should be screened for the R337H variant.