Abstract B147: The relationship between germline variants and clinicopathological characteristics in triple negative breast cancer patients from Colombia
Authors: Ordonez Yina Tatiana Zambrano , Vargas Laura Rey , Morales Paula Daniela , Serrano Silvia Juliana 
Published: December 2023

Introduction: Triple-negative breast cancer (TNBC) is the molecular subtype with the worst prognosis among breast tumors. It has been shown that the presence of germline variants can influence disease onset, progression, tumor biology, and other outcomes, however, to this date, the differences in clinical-pathological features according to germline variants in an admixed population like Colombian women, have not been yet explored. Therefore, the aim of this study was to explore the relationship between clinical-pathological characteristics and germline mutations in TNBC patients from Colombia. Methodology: This is a descriptive analysis that included 47 Colombian women with confirmed diagnosis of hereditary TNBC treated at the National Cancer Institute of Colombia, from 2008 to 2022. Germline mutations in 105 genes were assessed using the TruSigth multi-gene panel, and patients were divided according to the identified mutation into the following groups: BRCA1 carriers (n=18), BRCA2 carriers (n=13), homologous recombination (HR) gene carriers (n=13), and carriers of mutations in other genes (n=3). Fisher’s and Pearson’s chi-squared tests were used for categorical variables, and differences were considered statistically significant if p&lt;0.05. Results: Among our cohort, the identified mutation with the highest prevalence was the c.5123C&gt;A p. (Ala1708Glu) in the BRCA1 gene (36,9%). Regarding clinical-pathological features, we observed statistically significant differences in the distribution of germline mutations by age at diagnosis (p=0.042), body mass index (BMI) (p=0.04), and tumor differentiation (p=0.01). Women younger than 50 years at diagnosis had the highest frequency of BRCA1 (23,9%) mutations. Overweight (BMI: 25-30) and obese (BMI&gt;30) patients presented a higher proportion of mutations in the BRCA1 (15,2%) and BRCA2 (13,0%) genes, compared to patients with mutations in HR repair pathways (8,6%) and mutations in other genes (2,2%).  This is interesting as previous reports have shown an association between BRCA1/2 mutations with BMI and chronic inflammation, which could influence the development and progression of breast cancer. Poorly differentiated tumors (Bloom-Richardson: III) were more frequently observed in patients with BRCA1 mutations (32,6%), followed by patients with mutations in the HR genes (17,4%).  It is possible that this is related to the genetic changes that germline mutations induce within the tumor, which ultimately lead to a less differentiated disease. Conclusion: Our study confirms the greater proportion of mutations in BRCA1/2 genes in TNBCs among the Colombian population. The characterization of clinical-pathological characteristics of germline mutation-related tumors may help improve diagnosis, prognosis assessment, and targeted therapeutic approaches. Further studies with larger patient cohorts are needed to confirm our findings. Additionally, large-scale studies are also warranted to elucidate the landscape of germline mutations relevant to the Colombian population, along with its clinical implications.

Citation Format: Yina Tatiana Zambrano Ordonez, Laura Rey Vargas, Paula Daniela Morales, Silvia Juliana Serrano. The relationship between germline variants and clinicopathological characteristics in triple negative breast cancer patients from Colombia [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B147.