Effects of Omega-3 Supplementation on Ki-67 and VEGF Expression Levels and Clinical Outcomes of Locally Advanced Breast Cancer Patients Treated with Neoadjuvant CAF Chemotherapy: A Randomized Controlled Trial Report

Background: Omega-3 is a polyunsaturated fatty acid with an ability to regulate cell proliferation and apoptosis through interaction with inflammatory mediators. The potential additional beneficial effects of Omega-3 on chemotherapy patients with breast cancer is not yet completely revealed. Methods: A double-blind randomized control trial (RCT) involving a total of 48 locally advanced breast cancer patients was conducted. Ki-67 and VEGF expressions, as well as overall survival of patients receiving neoadjuvant cyclophosphamide-doxorubicin-5’fluorouracyl (CAF) chemotherapy plus Omega-3 (intervention group) or placebo (control group), were compared. Kaplan-Meier curve and Cox-regression tests were used to assess conditional disease-free survival (DFS) and overall survival (OS) between the two groups. Results: Decreased Ki-67 expression was observed in the intervention group compared to control (42.4±4.8 versus 39.2±5.3; T-test p=0.032). Decreased Ki-67 expression was observed in intervention compared to control group (42.4±4.8 versus 39.2±5.3; T-test p=0.032). Decreased VEGF expression was also seen in the intervention group compared to control (32.7±5.2 versus 29.5±5.4; T-test p=0.041). VEGF expression positively correlated with Ki-67 expression (Spearman’s test p<0.001, R2=0.541). Overall survival in the intervention group was significantly longer in comparison to the control group (mean survival: 30.9 ± 3.71 versus 25.9 ± 3.6 weeks, Mantel-Cox test p=0.048; HR=0.411, 95%CI: 0.201-0.840). Disease-free survival was significantly longer in the intervention group compared to the control group (mean survival: 28.5 ± 3.3 versus 23.7 ± 3.6, respectively; Mantel-Cox test p=0.044, HR= 0.439, 95%CI: 0.222-0.869). Conclusion: Omega-3 fatty acid supplementation improved overall survival and progression-free survival of locally advanced breast cancer treated with CAF neoadjuvant chemotherapy and mastectomy.