Diet and exercise for breast cancer patients
A randomised phase II trial of intermittent energy restriction and resistance exercise in women receiving chemotherapy for advanced breast cancer (B-AHEAD3).
Funding
Why this trial
Research has shown that energy restriction and weight control protect normal cells from the effects of chemotherapy whilst increasing the sensitivity of cancer cells to treatment - the so-called ‘differential stress response’. Many breast cancer patients are above an ideal weight and many patients gain fat and lose muscle during chemotherapy.
Too much fat and reduced lean body mass (fat-free body mass) have increased chemotherapy toxicity and poorer outcome. Weight loss is therefore recommended in breast cancer patients who are overweight.
The benefits of losing weight by diet have not been fully investigated in women with advanced breast cancer. This study was designed to assess the value of dietary restriction with respect to the effectiveness of chemotherapy to halt progression of the disease and the reduction of side effects.
If successful, this approach could have been widely used to help women with advanced breast cancer and possibly other cancers in the future.
Why this intervention
The main aim of dietary intervention is to reduce energy intake. Studies in animals indicate that energy restriction, mainly achieved by reduced carbohydrate intake, is associated with reduced tumour growth and progression.
In the trial outlined here, the approach used is intermittent energy restriction (IER). Previous studies suggest this may be the best way to achieve weight loss. Previous randomised trials in women without breast cancer indicate that IER is associated with greater weight loss, preservation of fat-free mass and other benefits, compared with standard continuous energy restriction (CER). The researchers developed an IER diet that involves two consecutive days of severe energy restriction and five days of normal healthy eating.
Trial design
In this randomised trial, 134 overweight women receiving chemotherapy for advanced breast cancer were planned to be assigned to one of two treatment groups. The women were recruited by 10 centres in the UK.
The first group (control group) would consist of 67 patients. Patients in this group received chemotherapy and followed a regular diet while taking part in resistance training three times a week.
The second group (the intervention group) was also planned to consist of 67 patients. The patients in this group followed the 5/2 diet whilst receiving chemotherapy. During the 2 restricted diet days, these patients were allowed a maximum caloric intake of 800 to 1000 kcal and 50 g of carbohydrates per day. The other five days, they followed a Mediterranean diet. This includes eating lots of fruits and vegetables, nuts, fish, low-fat dairy products, white meat and limited quantities of red meat. Patients also participated in resistance training 3 times per week.
The trial tested whether an energy restricted diet adds to the anti-tumour effect and lessens chemotherapy toxicity compared to a resistance exercise-only intervention.
Results
The trial recruited patients from May 2015 until the study closed during the COVID pandemic in March 2020. In total, 68 participants were enrolled over the 2 groups.
Analysis of the study data showed potential benefits of the 5/2 diet on progression free survival. Though not reaching statistical significance, the cancer of women in the 5/2 diet group did not get worse, on average, for 42 weeks, compared to 26 weeks in the exercise-only group. The 5/2 diet did not have any effect on the toxicity of chemotherapy, which was relatively low in both groups. There was a good adherence to the 5/2 diet which was associated with modest reductions in weight and abdominal fat, alongside improvements in quality of life.
The results of the B-AHEAD 3 trial suggest that further research into the 5/2 diet in advanced breast cancer (ABC) is well worth pursuing. A larger future study involving around 350 to 375 patients would be needed to reliably show whether this approach can delay cancer progression, with strong statistical confidence. This study would need to address the recruitment issues encountered in the B-AHEAD 3 trial beyond the ones caused by the COVID19 pandemics.
Results were published July 2025.
Partners
Researchers:
- Dr. Michelle Harvie, Genesis Breast Cancer Prevention Centre, Manchester University NHS Foundation Trust, Manchester, UK (Principal Investigator)
- Dr. Sacha Howell, University of Manchester and The Department of Medical Oncology, Manchester, UK
Sponsor:
- Manchester University NHS Foundation Trust, Manchester, UK
Our role
Why we support this trial
Intervention has little or no commercial value
Expected survival benefit
No major hurdle for clinical implementation
Funding
References
More info on Cancer Reseach UK: B-AHEAD3
Chlebowski, R.T., et al. (2006). Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women's Intervention Nutrition Study. J Natl Cancer Inst, 98(24):1767-76. doi:10.1093/jnci/djj494
Del Fabbro, E., et al. (2012). The relationship between body composition and response to neoadjuvant chemotherapy in women with operable breast cancer. The Oncologist 17(10):1240-5. doi: 10.1634/theoncologist.2012-0169
De Lorenzo, M.S., et al. (2011). Caloric restriction reduces growth of mammary tumors and metastases. Carcinogenesis, 32(9):1381-7. doi: 10.1093/carcin/bgr107
Harvie, M., et al. (2013). The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. The British Journal of Nutrition, 110(8), 1534-47. doi:10.1017/S0007114513000792
Lee, C., et al. (2012). Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer Cell Types to Chemotherapy. Science Translational Medicine, 4(124), 124ra27. doi:10.1126/scitranslmed.3003293
Author: Kristine Beckers (Trial Manager)
Last updated: August 2025