A specific diet has been developed that does not only pursue weight loss but also encompasses metabolic changes such as insulin sensitivity, blood pressure, cholesterol, etc." /> advanced breast cancer, overweight women, diet, dietary pattern | Anticancer Fund

B-AHEAD-3: a randomized phase-2 trial to determine the effect of a 2 day/week calorie/energy restricted diet and resistance exercise in women receiving chemotherapy for advanced breast cancer

Info

Location: Genesis Breast Cancer Prevention Centre University Hospital of South Manchester, United Kingdom
Collaboration: Michelle Harvie, PhD, researcher / dietitian ; Dr. Sacha Howell, Medical Oncologist, University of Manchester (UK) ; Professor Tony Howell, Medical Oncologist, University of Manchester (UK)µ

 

Being overweight or gaining weight due to cancer treatment may have a negative impact on the survival and quality of life of women with breast cancer. Weight loss is therefore recommended in breast cancer patients who are overweight.

 

M. Harvie and Prof Howell developed a diet that does not only pursue weight loss but also brings about beneficial metabolic changes such as improvements in insulin sensitivity, reduced blood pressure, cholesterol, etc. The diet involves a short period of caloric restriction. Such diets have been reported in animal studies to both lower tumour growth and progression as well as lowering the toxicity from chemotherapy. Yet this diet had to be feasible and motivate patients to see it through! This is how the 5/2 diet came to life. This diet prescribes 2 consecutive days of caloric restriction and five days of Mediterranean diet. During the 2 restricted days 2 days a maximum caloric intake of 800 to 1000 kcal and 50 g of carbohydrates per day is allowed.

The team of M. Harvie and Prof T. Howell had previously studied this diet in overweight women with a family history of breast cancer. In the first study 115 women participated. The group of women who followed the 5/2 diet showed the most weight loss and loss of body fat. In addition, they were also examined for other health factors such as improved insulin sensitivity, and other factors. Again, the results were better in the group following the 5/2 diet than standard conventional daily dieting.

Because of the positive results of this study, the team (M. Harvie, Prof. T. Howell and Dr S. Howell) decided to also study the diet in women with breast cancer at an early stage during treatment with chemotherapy, in their B-AHEAD-2 study (Breast Activity and Healthy Eating After Diagnosis 2). This study, which included 169 patients, was recently completed, and examined whether the 5/2 diet is feasible and effective to prevent chemotherapy-induced weight gain. It also examined the effects of the diet on chemotherapy toxicity. The results of the study are currently being analyzed and publication will follow early in 2017.

This team of researchers thought about taking it even further and to study the diet also in overweight women with advanced breast cancer who are receiving chemotherapy. This study is called the B-AHEAD 3 trial and is testing the effect of the 5/2 diet and resistance exercise on response to chemotherapy, chemotherapy toxicity and quality of life.

In this multicenter study (9 centers) 134 patients with advanced breast cancer are recruited and divided into 2 groups.
- The first group (control group) consists of 67 patients. Patients in this group receive chemotherapy and follow a regular diet. They also take part in resistance training 3 times a week. Resistance exercise is also known as strength training, and it is performed to increase the strength and mass of muscles, bone strength and help to maintain metabolic rate.
- The second group (the intervention group) also consists of 67 patients and follows the 5/2 diet whilst receiving chemotherapy. During these two days, these patients are only allowed a maximum caloric intake of 800 to 1000 kcal and 50 g of carbohydrates per day. The other five days they follow a Mediterranean diet. This includes eating lots of fruits and vegetables, nuts, fish, low fat dairy products, white meat and limited red meat. They also participate in resistance training 3 times per week.

This study will take three years and will examine the difference between the two groups concerning progression-free survival, toxicity due to chemotherapy, quality of life, fatigue, change in weight, waist circumference, and fat and muscle mass. All these factors will be assessed with the same CT scans used to assess tumour responses. Currently (February 2017) 20 patients are included in this study. 

 

For more information about the 5:2 day diet click here.

More details about this study at http://www.isrctn.com/search?q=bahead+3

Professional info

Location: Genesis Breast Cancer Prevention Centre University Hospital of South Manchester, United Kingdom
Collaboration: Michelle Harvie, PhD, researcher / dietitian ; Dr. Sacha Howell, Medical Oncologist, University of Manchester (UK) ; Professor Tony Howell, Medical Oncologist, University of Manchester (UK)

 

Being overweight or gaining weight due to cancer treatment may have a negative impact on the survival and quality of life of women with breast cancer. Weight loss is therefore recommended in breast cancer patients who are overweight.

However the benefits of such an approach have not been fully investigated in women who have the misfortune to have recurrent advanced breast cancer. This study is designed to assess the value of dietary restriction with respect to the effectiveness of chemotherapy to halt progression of the disease and reduction in side effects.

 

Michelle Harvie and Prof Anthony Howell developed a diet, the 5/2 diet, that is effective for weight loss but also produces greater potentially beneficial improvements in insulin sensitivity. The diet involves 2 days of caloric/energy restriction. Energy restriction and weight control have been shown in preclinical models to protect normal cells from the effects of chemotherapy and radiotherapy whilst increasing sensitivity in malignant cells via increased oxidative stress, apoptosis and DNA damage – the so-called ‘differential stress response’.

This is mediated by well characterized metabolic and signaling changes which affect both the supporting stroma and the tumor cells. Energy restriction reduces levels of host factors including insulin, insulin-like growth factor-1, leptin, adiponectin, steroid hormones, cytokines, vascular regulators, and inflammation related molecules, as well as the cellular and structural components of the tumour microenvironment including reduced hypoxia inducible factor-1 (HIF-1) and downstream gene expression [i.e. reduced haem oxygenase-1 (HO-1), vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS)], reduced reductive oxygen species and hydrogen peroxide. These secreted and structural host factors are extrinsic to, and interact with, the intrinsic molecular characteristics of breast cancer cells (including breast cancer stem cells). All these markers will be assessed to indicate the mechanism whereby energy restriction may reduce chemotherapy associated toxicity and increase the effectiveness of treatment.

The team of M. Harvie, Prof. T. Howell and Dr. S. Howell, want to study the diet in overweight women with advanced breast cancer who are receiving chemotherapy. In this study, B-AHEAD-3 (B-AHEAD-3: Breast-Activity and Healthy Eating After Diagnosis-3), they want to verify the effect of the 5/2 diet on survival and quality of life. The likely benefits of energy restriction in metastatic patients are suggested by beneficial effects of mTOR inhibitors. mTOR inhibitors are highly effective in increasing time to progression in advanced breast cancer, although with some toxicity. The working hypothesis of M. Harvie and her team is that weight loss and energy restriction in advanced disease will act in a similar manner to mTOR inhibitors and extend time to progression and, in contrast to mTOR inhibition, reduce toxicity and improve quality of life.

The 5/2 diet prescribes 2 consecutive days of caloric restriction and five days of Mediterranean diet. During those 2 days a maximum caloric intake of 800 to 1000 kcal and 50 g of carbohydrates per day is allowed.

In this multicenter study (9 centers) 134 patients with advanced breast cancer are recruited and divided into 2 groups:
- The first group (control group) consists of 67 patients . Patients in this group receive chemotherapy and follow a regular diet. They also take part in resistance training 3 times a week. Resistance exercise is also known as strength training, and it is performed to increase the strength and mass of muscles, bone strength and metabolic rate .
- The second group (the intervention group) also consists of 67 patients who will follow the 5/2 diet whilst receiving chemotherapy. During restricted diet days, these patients are only allowed a maximum caloric intake of 800 to 1000 kcal and 50 g of carbohydrates per day. The other five days they follow a Mediterranean diet. This includes eating lots of fruits and vegetables, nuts, fish, low fat dairy products, white meat and limited red meat. They also participate in resistance training 3 times per week.

This study will take three years and will examine the difference between the two groups in terms of progression-free survival, toxicity due to chemotherapy, quality of life, fatigue, change in weight, waist circumference, and fat and muscle mass. All these factors will be assessed with the same CT scans used to assess tumour responses. Recruitment of the patients started in May 2015. If successful this approach may be widely used to help women with advanced breast cancer and possibly other cancers. Currently (February 2017), 20 patients are included in this study.

 

For more information about the 5/2 day diet click here.

More details about this study at http://www.isrctn.com/search?q=bahead+3