T. C. Olsen1, L. Pack2, G. Ashji2, M. DeMagistris1, M. Noble2, J. I. Leckenby1 1University Of Rochester Medical Center, Plastic And Reconstructive Surgery, Rochester, NY, USA 2University Of Rochester Medical Center, Biomedical Genetics, Rochester, NY, USA
Introduction:
Breast cancer poses a significant global health challenge, particularly with the aggressive triple-negative breast cancer (TNBC) subtype. To advance treatment outcomes and pathophysiologic understanding of TNBC, it is necessary to improve upon commonly used experimental tumor models, such as patient-derived xenografts (PDXs), which fall short in recapitulating tumor-immune interactions due to their reliance on immunosuppression. To overcome this limitation, our study sought to establish a standardized treatment protocol for the widely adopted immunocompetent E0771 TNBC murine model by evaluating the efficacy of various adjuvant and non-adjuvant chemotherapy regimens in this context.
Methods:
16-week-old female C57BL/6 mice received hormone-resistant syngeneic murine breast cancer cells (E0771, ATCC®) in the right mammary fat pad. Surgical excision and/or intraperitoneal (i.p.) injections of Paclitaxel (PTX), Cisplatin (CP), or Vincristine (VCT) began upon tumor detection. Mice were grouped into five treatment arms: 1) Control (saline, n=3), 2) VCT (1.5mg/kg, 2 days/week, n=3), 3) PTX/CP (7.5mg/kg PTX, 5 days/week; 2.5 mg/kg CP, 1 day/week, n=5), 4) Surgery+PTX/CP (tumor excision followed by PTX/CP, n=2), and 5) Surgery (tumor excision without chemotherapy, n=2). In vitro dose-response curves confirmed E0771 sensitivity to PTX, CP, and VCT. Tumor growth rates were modeled via linear regression. Survival time (inoculation to death) was assessed using Kaplan-Meier curves with Log-Rank comparisons. Metastatic disease was evaluated via Fisher’s Exact Test. P<.05 represents significance.
Results:
PTX/CP, VCT, and saline treatments exhibited 37.1, 18.0, and 32.5 mm3/day faster tumor growth than surgery alone, and 41.3, 22.2, and 36.7 mm3/day increases compared to surgery+PTX/CP, respectively (p=<.001, .002, .006, <.001, <.001, .002). VCT-treated mice showed 19.1 mm3/day slower tumor growth than PTX/CP (p=.016). Surgery+PTX/CP had a numerically lower tumor growth rate (4.2 mm3/day) than surgery alone (p=.237). Survival times were similar between surgery groups (p=.808), but surgical intervention correlated with prolonged survival compared to PTX/CP, VCT, and saline (p=.027, .036, .048). Overall, survival differed significantly among the five groups (p<.001, Figure 1), while metastatic disease did not (p=.820).
Conclusion:
Among the treatment arms, surgery before Paclitaxel and Cisplatin (surgery+PTX/CP) demonstrated the slowest tumor growth and significantly lengthened survival compared to non-adjuvant treatments, suggesting its potential for developing an adjuvant chemotherapy regimen for the E0771 model. Our findings warrant future investigation with larger samples and additional adjuvant treatments.
