publication date: Mar. 2, 2018
Trials and Tribulations
A phase III trial seeks to determine whether diet and exercise can cure breast cancer
By Jennifer A. Ligibel
Director of the Leonard P. Zakim Center for Integrative Therapies and Healthy Living, Senior physician at the Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School
Could diet and exercise really cure breast cancer?
For more than 50 years, studies have shown that women who are obese at the time of breast cancer diagnosis have an increased risk of cancer recurrence and mortality, as compared to women who are leaner at diagnosis.
Animal models have shown that caloric restriction and increased physical activity prevent breast tumor formation and slow cancer growth. Dietary intervention studies in women with early breast cancer suggest that reduction in dietary fat intake, combined with modest weight loss, leads to a reduction in the risk of breast cancer recurrence whereas dietary fat reduction without weight loss does not impact prognosis.
This research has contributed to the countless headlines promising patients that eating organic/vegan/paleo/keto/etc. will prevent their cancer from recurring, but the actual evidence that changes in diet and exercise after diagnosis could affect outcomes in women with breast cancer has been scant.
Now, a randomized trial will test the impact of a weight loss program, based on caloric restriction and increased exercise, on the risk of cancer recurrence and mortality in overweight and obese women with breast cancer.
The Breast Cancer Weight Loss (BWEL) trial is a phase III trial, sponsored by the Alliance for Clinical Trials in Oncology, that will enroll 3136 women with newly diagnosed breast cancer and a BMI of at least 27 kg/m2 and randomize them to a telephone-based weight loss intervention or health education control group. The trial is powered to detect a 20% improvement in invasive disease-free survival in the weight loss group versus controls. The weight loss program is based upon the Diabetes Prevention Program; however, unlike the DPP, which was delivered in person in small groups, we designed the BWEL weight loss program to be delivered through the telephone and web, making the program accessible to a diverse population of breast cancer survivors across the US and beyond.
The trial also includes a translational component to explore the mechanisms underlying the obesity-cancer link. Participants in both groups undergo serial collection of fasting blood throughout the intervention period to follow changes in metabolic, immune and inflammatory pathways. Tumor and benign tissue from participants’ breast surgery is also collected to explore predictive biomarkers for the effect of the weight loss program, providing critical information not only about whether the program works, but also in whom it is most successful in reducing the risk of recurrence and mortality.
It is always difficult to predict the adoption of a randomized trial, especially a trial like BWEL that tests an unconventional treatment program. In designing the trial, we had hoped to enroll patients in over about 4 years, recognizing that a recruitment rate of almost 800 patients per year was an ambitious goal for the first large scale lifestyle intervention study conducted by the Alliance. We were hopeful when the first patient was registered the day after the study opened in August of 2016 and have been incredibly gratified to continue to experience robust enrollment, with more than 1000 participants, representing 48 states and 2 Canadian provinces, randomized within the first 17 months after study activation. BWEL has also resonated outside the oncology community, attracting a number commercial partners not typically involved in oncology studies, including Fitbit and Nestlé Health Science, who have made in-kind product donations of activity trackers, wireless scales and protein meal replacements to support participants in achieving weight loss goals.
This in-kind support has been especially helpful given the complex funding considerations of the trial. Given that the study is being conducted through the Alliance and was approved by the Breast Cancer Steering Committee, funding for central administrative costs and per-patient reimbursement is supported by CTEP.
However, there is no funding for lifestyle interventions through this mechanism. Two other NCI divisions, DCP and DCCPS have supported most of the costs of administering the BWEL weight loss program, but the brisk rate of accrual and unanticipated costs associated with conducting a large-scale lifestyle intervention trial in multiple countries and languages has led to the need for other groups, such as the Susan G. Komen Foundation, the Breast Cancer Research Foundation, and the American Cancer Society to also provide financial support to ensure a consistent and robust weight loss intervention for study participants. Successful conduct of this trial has thus required extensive collaboration across the breast cancer community and beyond.
Over the next few years, the BWEL study will finally give us conclusive evidence of the impact of changes in diet and exercise on breast cancer recurrence and mortality. Early signs from the study suggest that patients are eager to incorporate lifestyle changes into their cancer treatment, allowing them to play a more active role in their care and hopefully to help establish a new standard of care for the generations of breast cancer patients who follow them.