Abstract P3-13-08: Modification of the response to chemotherapy of HER2 negative metastatic breast cancer by lipids of marine origin: A controlled, randomized, double blind dietary supplementation trial
Authors: Bougnoux Philippe , Bonneterre Jacques , Mercier-Blas Anne , Soulié Patrick , Simon Hélène , Priou Franck , Piprot-Choffat Christine , Levy Christelle , Goupille Caroline , Berger Virginie 
Published: May 2015

Abstract
Background: Long chain n-3 Polyunsaturated Fatty Acids (n-3 PUFA) of marine origin (docosahexaenoic acid, DHA and eicosapentaenoic acid, EPA) have been shown to increase sensitivity of cell lines to anthracyclins or taxanes. Preclinical studies and a phase II clinical trial have shown that increasing DHA level in the body tissues through a dietary supplementation improves chemotherapy efficacy. We have set up a phase III controlled, double blind study to determine whether a dietary supplementation with n-3 PUFA would increase PFS in patients receiving chemotherapy for metastatic breast cancer (MBC).
Methods: Inclusion criteria were patients with a ductal or lobular breast carcinoma, positive hormone receptors, Her2 (-), who have developed visceral metastasis, and were due to receive a 1st or 2d line chemotherapy. Dietary intervention was carried out during chemotherapy. Patients had to take daily at each meal a can* (medical food) containing either fish oil (1.56 g/d of DHA and 2.64 g/d EPA, experimental arm) or coprah oil (short chains fatty acids, control arm). Principal endpoint was PFS, secondary were objective response, overall survival, dietary tolerance to cans, lipids plasma levels of n-3 PUFA.
Results: Sixty five patients with MBC have been prospectively enrolled in the DHALYA trial (NTC01548534). The first 45 patients who completed chemotherapy along with dietary supplementation are evaluable. Plasma fatty acid level was measured at baseline, at C1 after 10 days loading dose, at C3, and at C6 or at withdrawal. Level of EPA and DHA increased in half of the patients, thus allowing a putative allocation into either arm: arm A with induced elevation of PUFA levels (N=22), and arm B without any change in PUFA levels (N=23). No difference was observed in the quality of the dietary intervention (number of cans, duration) among arms. Distribution of patients according to demographics (age, menopausal status, histology, SBR grade), or type or quality of chemotherapy received (anthracycline- or taxane-based, number of cycles, length) was similar between arms. However a significantly greater proportion of patients with poor prognosis at staging (larger tumor size and greater axillary lymph nodes involvement) were observed in arm A. There was no difference in side effects (grade ≥2) between arms. In terms of efficacy, median PFS was 14.3 (arm A) and 12.5 (arm B) months, not statistically different yet.
Conclusion: A dietary intervention targeted on marine-derived PUFA during systemic chemotherapy for MBC is safe and feasible. A longer follow-up is required in order to know whether chemotherapy efficacy can be increased.
This study was supported by a grant from the French Ministry of Health, PHRC-11-153. *Cans were graciously provided by Nutrialys Medical Nutrition, Saint Grégoire, France.
Citation Format: Philippe Bougnoux, Jacques Bonneterre, Anne Mercier-Blas, Patrick Soulié, Hélène Simon, Franck Priou, Christine Piprot-Choffat, Christelle Levy, Caroline Goupille, Virginie Berger. Modification of the response to chemotherapy of HER2 negative metastatic breast cancer by lipids of marine origin: A controlled, randomized, double blind dietary supplementation trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-13-08.