Dados do Trabalho

Título

CHEMOBIOGRAM: TESTE DE QUIMIORRESISTENCIA IN VITRO DO CANCER DE MAMA

Título em Inglês

IN VITRO BREAST CANCER CHEMORESISTANCE TEST

Introdução

Tumor resistance is the main cause of treatment failure leading to cancer progression and is classified into intrinsic and acquired resistance. The intrinsic resistance is related to a preexisting condition and the acquired resistance is induced by a drug. Some methods are already available worldwide to assess drug resistance, however, in Brazil no in vitro chemoresistance test for cancer is validated for use in the clinic.

Objetivos

The aim of our study is to validate the in vitro chemoresistance test Chemobiogram for the drugs used in breast cancer (BC) treatment. An incomplete response to neoadjuvant treatment was used to validate the results at a short-term follow-up and treatment after primary BC will be used to validate the test in a long-term follow-up.

Métodos

Patients with invasive breast cancer were included in this initial report. Fresh tumor samples were collected during surgery and subsequently dissociated to obtaining the tumor cells. The tumor cells were cultured in a 96 well plate with the several drugs used for BC treatment, including cytotoxic, hormonal, anti-HER2, and target therapies, and after 72h cell viability was evaluated. The test result is defined based on cell viability as low (< 40%), medium (40-60%), and high (> 60%) resistance. The test result is compared to the patient`s response to the treatment.

Resultados

To validate the dissociation and BC primary culture techniques we collected samples from 6 patients with in situ and invasive tumors. These samples were not tested in Chemobiogram. Samples from 5 BC patients undergoing neoadjuvant treatment and from 3 patients with primary BC were tested in the Chemobiogram. Of the 5 patients who underwent neoadjuvant treatment, 2 performed hormone therapy and 3 chemotherapy. Four patients presented incomplete response to the treatment and one patient who performed neoadjuvant chemotherapy presented disease progression during the treatment. The chemoresistance test was able to demonstrate medium to high resistance for the drugs used in the neoadjuvant treatments (acquired resistance).
The 3 patients with primary BC were diagnosed with Luminal tumors-HER2 negative. In the chemoresistance test all samples presented medium to high resistance to anti-HER2 drugs (intrinsic resistance) and low to medium resistance to cytotoxic drugs. These patients will be followed in the long-term to compare patient outcomes with the test result.

Conclusões

The primary culture of breast tumors was efficiently established and the preliminary result of the chemoresistance test was in agreement with the outcomes from 5 patients who underwent neoadjuvant treatment. This preliminary finding showed the capacity of the Chemobriogram to demonstrate drug resistance in accordance with the clinic and highlighted the importance of the in vitro chemoresistance test to avoid the use of inefficient drugs improving and personalizing breast cancer treatment.

Palavras Chave

Breast cancer
Drug resistance
Primary cell culture

Área

TUMOR CELL, MOLECULAR BIOLOGY, PREDICTIVE AND PROGNOSTIC FACTORS - Tumor cell, molecular biology, predictive and prognostic factors – other