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

Abstract

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.

N-3 Long-Chain Polyunsaturated Fatty Acids, Eicosapentaenoic and Docosahexaenoic Acid, and the Role of Supplementation during Cancer Treatment: A Scoping Review of Current Clinical Evidence

“…A spectrum of cancers including breast [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ], head and neck [ 15 , 17 , 18 , 19 ], gastrointestinal [ 14 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ], gastric [ 21 , 28 , 29 , 30 , 31 ], colorectal/rectal [ 21 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ], esophageal [ 15 , 19 , 21 , 46 , 47 ], leukemia/lymphoma [ 48 ], lung [ 14 , 15 , 21 , 40 , 49 ,...…”

“…Of the total supplementation, DHA concentrations ranged from 0 to 2 g, with 86% of the studies providing 1 g or less per day. When capsules were provided concomitant with chemotherapy the intervention length was 6–24 weeks and equivalent to the duration of chemotherapy [ 7 , 8 , 9 , 10 , 11 , 16 , 20 , 26 , 27 , 30 , 31 , 32 , 33 , 34 , 45 , 48 , 49 , 50 , 51 , 56 , 63 ]. In the absence of chemotherapy, supplementation was provided for 1–6 months [ 12 , 13 , 14 , 35 , 36 , 52 , 57 ].…”

“…A spectrum of cancers including breast [7][8][9][10][11][12][13][14][15][16], head and neck [15,[17][18][19], gastrointestinal [14,[20][21][22][23][24][25][26][27], gastric [21,[28][29][30][31], colorectal/rectal [21,[32][33][34][35][36][37][38][39][40][41][42][43][44][45], esophageal [15,19,21,46,47], leukemia/lymphoma [48], lung [14,15,...…”

Mechanistic Targets and Nutritionally Relevant Intervention Strategies to Break Obesity–Breast Cancer Links

“…Omega-3 fatty acids have been linked to protective roles in breast cancer progression, such as the inhibition of angiogenesis and metastasis ( Figure 1 ). Additionally, several studies have suggested an association between a higher omega-3 intake and a lower risk of breast cancer ( 129 , 130 ). Supplementation of omega-3 fatty acids in women undergoing surgery for locally advanced, invasive carcinoma resulted in decreased expression of both Ki-67 and VEGF compared to a control group ( 130 ).…”

“…Additionally, several studies have suggested an association between a higher omega-3 intake and a lower risk of breast cancer ( 129 , 130 ). Supplementation of omega-3 fatty acids in women undergoing surgery for locally advanced, invasive carcinoma resulted in decreased expression of both Ki-67 and VEGF compared to a control group ( 130 ). Furthermore, the omega-3 fatty acid supplementation group displayed a longer disease-free survival and overall survival ( 130 ).…”