RESUMO
DNA repair is a key determinant in the cellular response to therapy and tumor repair status could play an important role in tailoring patient therapy. Our goal was to evaluate the mRNA of 13 genes involved in different DNA repair pathways (base excision, nucleotide excision, homologous recombination, and Fanconi anemia) in paraffin embedded samples of triple negative breast cancer (TNBC) compared to luminal A breast cancer (LABC). Most of the genes involved in nucleotide excision repair and Fanconi Anemia pathways, and CHK1 gene were significantly less expressed in TNBC than in LABC. PARP1 levels were higher in TNBC than in LABC. In univariate analysis high level of FANCA correlated with an increased overall survival and event free survival in TNBC; however multivariate analyses using Cox regression did not confirm FANCA as independent prognostic factor. These data support the evidence that TNBCs compared to LABCs harbour DNA repair defects.
Assuntos
Reparo do DNA/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia de Fanconi/genética , Feminino , Recombinação Homóloga/genética , Humanos , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Estrogênio/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Breast cancer is a heterogeneous disease. Predictive molecular markers are crucial in patient management, but the only recommended predictive biomarkers are estrogen and progesterone receptors and HER2. There are many new targeted therapies, and although the target pathway expression is readily analyzed on conventional pathology, the dynamic response cannot be assessed and pathway expression is no guarantee it has a major driver role, even if mutated. Selecting therapies requires considering the patient, the molecular characteristics of the tumor, and the microenvironment of the tumor. Thus, the integration of molecular pathology, imaging, and early tumor biological response to therapy may provide evidence of drug activity and allow more rapid changes of therapy. The adaptive response of the tumor is a key resistance mechanism that can be assessed readily in the neoadjuvant setting. Although there are no markers that meet all surrogacy criteria, their use could provide crucial information on mechanisms of drug sensitivity/resistance. Validation of such markers requires a major emphasis on neoadjuvant trials to relate early-biomarker response to outcome.