62. Analysis of Adjuvant and Non-Adjuvant Chemotherapy Regimens in an Immunocompetent Triple-Negative Breast Cancer Model: Implications for Treatment Optimization

PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options and a poor prognosis. Current preclinical models, primarily patient-derived xenografts (PDXs), are limited by their lack of a functional immune system, hindering insights into immune-tumor dynamics. This study aims to address this gap by evaluating standardized chemotherapy regimens using the immunocompetent E0771 TNBC murine model, assessing the effects of adjuvant and non-adjuvant therapies on tumor progression and survival. METHODS: Twenty-five female C57BL/6 mice were orthotopically implanted with E0771 cells into the right mammary fat pad. Upon tumor detection, mice were divided into treatment groups, including Saline, Vincristine (VIN), Paclitaxel/Cisplatin (PTX/CSP), Surgery Alone, Surgery + (PTX/CSP), and Surgery + (PTX/CSP/VIN). The efficacy of PTX, CSP, and VIN was confirmed in vitro, followed by in vivo assessments of tumor growth, survival, and metastatic incidence. Growth rates were analyzed using a Gaussian regression model and a linear regression model was applied to log-transformed tumor volume rates. Survival outcomes were assessed using the log-rank test for unadjusted comparisons of time-to-event data. The incidence of metastatic disease was evaluated using Fisher’s Exact Test (two-tailed). Statistical significance was set at P < 0.050. RESULTS: Surgical resection combined with adjuvant PTX/CSP or PTX/CSP/VIN significantly reduced tumor growth by 204.1 mm³·day⁻¹ (P = 0.041) and 162.9 mm³·day⁻¹ (P = 0.041), respectively, compared to the control. Linear regression analysis of log-transformed tumor volume rates showed reduced growth for surgical resection with adjuvant PTX/CSP (-3.4793 mm³·day⁻¹, P = 1.87e-9) and PTX/CSP/VIN (-2.8609 mm³·day⁻¹, P = 7.50e-10) compared to saline. Surgical resection alone extended median survival to 52.0 days (P = 0.002) while adding adjuvant PTX/CSP/VIN further increased survival to 68.0 days (P = 0.007) compared to 23.0 days for saline. No significant differences in metastatic incidence were observed across groups (P = 0.492). CONCLUSION: Surgical resection, particularly when combined with adjuvant chemotherapy, significantly reduced tumor growth and extended survival in this immunocompetent murine TNBC model. These findings underscore the role of surgery as a critical component of TNBC management when paired with effective adjuvant regimens. Although recurrence and metastasis were not entirely prevented, this study provides a foundation for optimizing adjuvant strategies to improve oncologic outcomes. Additionally, the implications for reconstructive surgery must be considered, as prior chemotherapy affects tissue quality, vascular integrity, and overall reconstructive options, directly influencing surgical decision-making. Future research should further enhance adjuvant therapies to maximize oncologic control and facilitate reconstructive planning, ultimately improving patient outcomes.