A Randomised Study of Docosahexaenoic Acid (DHA) in Metastatic Breast Cancer

Local relapses and metastases make breast cancer a deadly disease. A major goal remains the improvement of treatment efficacy, meaning increasing toxicity to tumor tissue, without additional toxicity to non-tumor tissues.

The literature indicates that DHA sensitizes breast malignant tumors, but not non-tumor tissues, to chemotherapy and to radiotherapy through a variety of mechanisms. DHA enrichment of tissues can be achieved through a dietary supplementation of DHA-containing oils, such as fish oil, both in experimental animal models or in humans. Therefore, this represents an original nutritional approach to increase the activity of anticancer treatments through an enhanced specificity toward tumor tissues.

• Dietary supplementation with fish oil. (Dietary supplement): Patients randomized in this arm will take 3 cans/day with fish oil : DHA is 1.56 g/d and EPA is 2.64 g/d.
• Dietary supplementation with vegetable oil (Dietary supplement): Patients randomized in this arm will take 3 cans/day with vegetable oil : no DHA no EPA.

Primary outcomes

• Progression Free Survival (PFS) [4 months]: PFS is defined as time from randomization to disease progression or death.

Secondary outcomes

• Objective Response Rate (ORR) [The objective response is the best objective response observed from the start of treatment to progression.]: ORR will be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).
• Overall Survival (OS) [3 years after last chemotherapy in study]: OS is defined as time from randomization to death due to any cause.
• Time To Progression (TTP) [First progression]: TTP is defined as time from randomization to first documentation of objective tumor progression according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).
• Safety ans tolerance of dietary supplementation/chemotherapy association [4 months]: Incidence and severity of adverse events will be assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
• Dietary supplementation compliance [4 months]: Compliance will be assessed through patient's diary.
• Quality Of Life (QOL) [At C1, after 4 months of chemotherapy, and at the end of chemotherapy.]: QOL will be assessed by QLQ-C30 and BR23 questionnaires.
• Pain evaluation [4 months]: Pain will be assessed by a Visual Analog Scale (VAS) and analgesic consumption.
• DHA plasma level [Before dietary supplementation (at C1), and after 4 months of dietary supplementation.]: Plasma phospholipids DHA incorporation will be measured with a blood sample.
• Neuropathy evaluation [4 months]: Neuropathy will be assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.

Sex: Female, ages: 18 Years to 80 Years

Inclusion Criteria:

* Metastatic breast cancer requiring first-line taxanes or anthracyclines based chemotherapy
* HER2 negative, HR positive
* Life expectancy > 3 months
* ECOG Performance Status < or = 2 within 15 days before randomization
* Measurable and/or evaluable disease according to RECIST criteria 1.1
* Age > or = 18 years and < or = 80 years
* Body Mass Index (BMI)>17 for patients < 70 years and BMI>21 for patients > 70 years, within 15 days before randomization
* Hepatic parameters : total bilirubin strictly normal, AST and ALT < or = 3xULN (5 if liver metastases) within 15 days before randomization
* Signed written informed consent

Exclusion Criteria:

* Triple negative breast cancer or HER2 over expression
* Symptomatic central nervous system metastases
* Previous chemotherapy for metastatic breast cancer
* Obesity with BMI > 35 within 15 days before randomization
* Presence of another invasive cancer
* Uncontrolled Cardiac disease or uncontrolled hypertension
* Milk protein intolerance
* Known food allergy to fish
* Women of childbearing potential not using adequate contraceptive measures, pregnant or breast feeding.

• Philippe Bougnoux, MD, PhD, Principal investigator, University Hospital, Tours