Interaction between inulin supplementation and cyclophosphamide therapy in patients with breast cancer

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Cyclophosphamide is one of the major drugs used in the treatment of breast cancer, however it has adverse effects that influence the quality of life, the response to cancer therapy and disease prognosis. The family of enzymes "Glutathione S-transferase" (GST) is essential for carrying out detoxification reactions from cyclophosphamide chemotherapy, allowing proper excretion of the drug. For this reason these enzymes are essential in the occurrence and degree of adverse effects resulting from drug chemotherapy. However, little is known about chemotherapy adjuvants to reduce the appearance of side effects such as leukopenia, nausea, vomiting, diarrhea and anorexia. In particular, inulin, an indigestible carbohydrate, generates short-chain fatty acids (SCFA) through colonic fermentation. SCFA may decrease the progression of leukemia in vitro, diarrheal episodes and anorexia. They also increase life expectancy by 70% in animal models treated with cyclophosphamide and synergistically supplemented with inulin. It also has important benefits such as stimulating the growth of probiotics in the colon like Bifidobacterium and Lactobacillus, and decreasing pathogenic microorganisms like Clostridium coccoides. Moreover, inulin fermentation enhances mucus production, ion absorption, bicarbonate formation in HIV patients and decreased serum triglycerides in patients with hypercholesterolemia. Consequently, these substances modulate immune function, possibly by improving health, quality and life expectancy. The hypothesis of this study is that inulin supplementation after cyclophosphamide therapy in patients with breast cancer modulates GSTT1, GSTM1 and GSTP1 mRNA and reduces gastrointestinal adverse reactions. The aims of this study are: 1. To determine whether mRNA of GSTT1, GSTM1 and GSTP1 in lymphocytes from patients under cyclophosphamide therapy is modified upon inulin supplementation; 2. To determine whether inulin supplementation reduces gastrointestinal adverse effect of cyclophosphamide therapy. In order to prove that, we designed a randomized triple blind study where a group of female breast cancer patients from the ISSEMyM State Cancer Center will be supplemented with inulin (15g/day) for 21 days after cyclophosphamide administration. Simultaneously, a second group of patients will receive maltodextrine for the same period of time as a control. The results of this study will provide insights about the utilization of inulin as a potential prebiotic adjuvant during chemotherapy and the mechanistic role of GST in the detoxification process upon cyclophosphamide exposure in humans.