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

Document Type: Research Articles

Authors

1 Department of Surgery, Dr. Kariadi Hospital, Faculty of Medicine, University Diponegoro, Semarang, Indonesia.

2 Division of Surgical Oncology, Department of Surgery, Dr. Sardjito Hospital, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.

3 Graduate School in Medicine and Health, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia.

4 Department of Surgery, Dr. Moewardi Hospital, Universitas Sebelas Maret, Surakarta, Indonesia.

5 Department of Anatomical Pathology, Dr. Sardjito Hospital, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.

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.

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