Abstract PO3-15-02: TP53 GENE POLYMORPHISM AT CODON 72 AS A RESPONSE PREDICTOR FOR NEOADJUVANT CHEMOTHERAPY
Authors: Jussane Vieira, Afonso Nazário, João Pesquero
Journal: Cancer Research (2024)

Abstract Introduction: Breast cancer is one of the most prevalent in women in the world and has shown extensive changes in treatment in recent decades. More patients are undergoing neoadjuvant chemotherapy in order to achieve pathological complete response (CPR) and perform less aggressive surgeries. CPR increases overall and disease-free survival and the decrease in tumor size increases the chances of conservative surgery. We have numerous studies that propose to discover CPR markers. Predictive factors of response to chemotherapy are important for treatment planning and the P53 gene, apoptosis-inducing gene, plays a role in inducing response to chemotherapy drugs that act by inducing apoptosis. The presence of mutations and genetic polymorphisms act by modulating this response. Among these, the codon 72 polymorphism is one of the most studied, as its polymorphic variants Arg/Arg, Arg/Pro and Pro/Pro encode a p53 with different functioning at the cell level. So, individuals with different polymorphisms will have different apoptotic action and different response to chemotherapy treatments. Objectives: Based on this knowledge, the study sought to correlate the polymorphism variants at codon 72 with the complete pathological response to neoadjuvant chemotherapy. Casuistic and Methods: The study was carried out at an oncology center in the state of Sergipe, in northeastern Brazil. A total of 206 patients with breast cancer who underwent neoadjuvant chemotherapy and core needle biopsy of the breast at the beginning of treatment were included in the stud,in the period from 2019 to 2022. From these patients, oral swab samples were collected for PCR evaluation of the P53 polymorphism at codon 72. The polymorphisms were studied using the Sanger technique at the Sao Paulo School of Medicine of the Federal University of São Paulo (UNIFESP). Patients were prospectively evaluated after surgery to verify the surgical pathological response after chemotherapy. Pathologic response was assessed using the RECIST criteria. The study was evaluated and approved by the ethics and research committee of UNIFESP and all patients signed an informed consent form. Results: Of the 206, 18.4% met the exclusion criteria (did not undergo surgery, interrupted chemotherapy treatment, insufficient genetic material in the swab, loss of follow-up). Of the 168 patients analyzed, 44.6% were Arg/Arg, 17.3% Pro/Pro and 38.0% Arg/Pro. Complete pathological response (PCR) was obtained in 21.4% of the patients, 10.1% had progressive disease (PD), 13.7% had stable disease (SD) and 54.2% had partial pathological response (PPR). Of the patients who achieved RPC, 47.2% were Arg/Arg, 38.9% Arg/Pro and 13.9% Pro/Pro without statistical significance, among the variants of polymorphisms. The only predictor of CPR in multivariate regression was immunohistochemistry (p&amp;lt; 0.001). The only predictor of CPR in multivariate regression was immunohistochemistry (p&amp;lt; 0.001) Conclusion: The P53 polymorphism at codon 72 is not a predictor of complete pathological response, but the Arg/Pro and Pro/Pro polymorphisms increase the chances of stable disease after neoadjuvant chemotherapy. Citation Format: Jussane Vieira, Afonso Nazário, João Pesquero. TP53 GENE POLYMORPHISM AT CODON 72 AS A RESPONSE PREDICTOR FOR NEOADJUVANT CHEMOTHERAPY [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-15-02.