Dados do Trabalho

Título

DRUG RESISTANCE IN PRIMARY INVASIVE BREAST TUMORS: RESULTS OF A NOVEL IN VITRO BREAST CANCER CHEMORESISTANCE PLATFORM

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59609822.4.0000.5530

Introdução

The use of in vitro functional tests, such as chemoresistance assays, can be useful for predicting tumor response to chemotherapy drugs. Chemoresistance tests aim at identifying ineffective agents to which the tumor is resistant, and this approach allows a more efficient and less cytotoxic treatment for patients. However, in Brazil, no in vitro chemoresistance test for cancer is validated for use in the clinic.  

Justificativa

Chemotherapy is one of the main treatments for breast cancer, however, it also has limitations owing to toxicity and tumor resistance to the drugs used. Thus, individualized treatment based on personal tumor characteristics is essential for improving therapeutic outcomes and patient survival.

Objetivo

Our preliminary study aims to validate the efficacy of a novel in vitro chemoresistance platform to demonstrate tumor resistance in primary invasive breast cancer.

Métodos

Patients with invasive BC who underwent upfront surgery were included. Fresh tumor samples were collected during biopsy or surgery and dissociated to obtain the tumor cells. The tumor cells were cultured in the chemoresistance platform with doxorubicin, epirubicin, paclitaxel, docetaxel, cyclophosphamide, and cisplatin, 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.

Resultados

Samples from 20 primary tumors were tested in the chemoresistance platform. The majority of tumors collected during upfront surgery were Luminal A (50%), followed by Luminal B (30%), Luminal B/HER2+ (15%) and HER2+ (5%). None of the tumors was triple-negative breast cancer. The mean patient’s age was 57,2 years. Eighteen (90%) underwent breast conserving surgery and sixteen (80%) sentinel lymph node biopsy. Half of the patients received adjuvant chemotherapy. During a median follow-up of 6 months, no recurrence was observed. The chemoresistance platform revealed that the tumors exhibited more high resistance to taxanes compared to anthracyclines, cyclophosphamide, and cisplatin. Specifically, 77.7% of the samples presented high resistance to docetaxel, 70% to paclitaxel, 20% to doxorubicin, 15% to epirubicin, 53% to cisplatin and none of the tumors showed high resistance to cyclophosphamide. Interestingly, Luminal A tumors showed a higher rate of high resistance to docetaxel (90%) compared to paclitaxel (60%), while Luminal B tumors presented the opposite pattern, with 66.6% exhibiting high resistance to docetaxel and 83.3% to paclitaxel. This finding demonstrated that the platform might assist in selecting drugs when two similar options are available.

Conclusão

These preliminary findings highlighted the technique success of the in vitro chemoresistance platform in demonstrating a distinct pattern of drug response in primary tumors suggesting a role of intrinsic resistance in the differential response to treatments commonly used for breast cancer.