Clinical, histopathological, and molecular biomarkers in a multicentric cohort of Mexican women with triple-negative breast cancer.
Authors: Hernandez Hernandez Jesus Edgardo , Mohar Alejandro , Lara-Torres César Octavio , Aranda-Gutierrez Alejandro , Vazquez Juarez Daniela , Velazquez-Martinez Areli , Cabrera-Galeana Paula Anel , Gómez-Macías Gabriela Sofía , Porras Reyes Fany Iris , Pérez Sánchez Víctor Manuel , Villarreal-Garza Cynthia 
Published: June 2024

e13152

Background: Triple negative breast cancer (TNBC) is a heterogeneous entity with a marked variation in biological behavior, treatment responses, and patient outcomes. Thus, the investigation of clinical, histopathological, and molecular biomarkers is essential to understand this variability and potentially inform more effective management approaches across different patient profiles. Methods: We conducted a retrospective multicenter study of women >18 years diagnosed with TNBC between 2006 and 2021 in two Mexican centers. We systematically gathered clinical and histopathological data, including an assessment of H&E-stained slides for histopathological features and tumor-infiltrating lymphocytes (TILs), alongside immunohistochemistry analyses for androgen receptors (AR), CD8, and doublecortin-like kinase 1 (DCLK1). Statistical analyses were conducted using R version 4.3.2. Results: In our cohort, comprising 289 patients, the average age at diagnosis was 49.13 years, with a median overall survival (OS) of 63 months and a 5-year OS rate of 55%. The distribution of clinical stages at diagnosis was as follows: I (n=12, 4.2%), II (n=94, 32.5%), III (n=130, 45.0%), and IV (n=53, 18.3%). CD8 expression was higher in patients with no recurrence compared to patients with stage IV at diagnosis (p<0.001), and it decreased with advancing clinical stages. We also found statistically significant differences in OS between negative and positive CD8 expression, favoring the latter (5-year OS 51.8% vs. 72.2%, p=0.032). Disease-free survival (DFS) and OS also differed significantly between low (≤10%) and high (>10%) stromal TILs, favoring the high expression group (5-year DFS 51.9% vs. 70.8%, p=0.0066; 5-year OS 50.1% vs. 70.3%, p=0.0018). CD8 levels positively correlated with stromal and intratumoral TILs. Positive AR expression (>10%) was seen in 8.9% of cases, with no observed differences in DFS or OS according to negative or positive status (5-year DFS 56.0% vs. 72.2%, p=0.42; 5-year OS 55.0% vs. 60.3%, p=0.68). Finally, DCLK1 positivity (≥10%) was seen in 23% of cases, with no influence on survival (negative vs. positive status, 5-year DFS 58.5% vs. 53.8%, p=0.63; 5-year OS 54.6% vs. 58.1%, p=0.60). Conclusions: Our study underscores the prognostic significance of CD8 and TILs in predicting DFS and OS among TNBC patients. Notably, the expressions of AR and DCLK1 were not independently associated with survival, although their prognostic impact in combination with other biomarkers is still an area of active research. Overall, our findings advocate for a more detailed examination of the molecular characteristics of TNBC within our demographic, encompassing an expanded array of biomarkers and a thorough investigation of the tumor microenvironment.