ProBE-TDR
Research type
Research Study
Full title
Prevention of breast and endometrial cancer using total diet replacement
IRAS ID
274621
Contact name
Sacha Howell
Contact email
ISRCTN Number
ISRCTN15358157
Duration of Study in the UK
3 years, 3 months, 1 days
Research summary
Summary of Research:
There are strong positive associations between adult body mass index (BMI) and both breast cancer (BC) and endometrial cancer (EC). However, the mechanisms by which obesity increases and dietary intervention reduces risk are not clear. Total diet replacement (TDR) has been shown to reduce cell division in the colon, potentially reducing cancer risk, and to reverse type 2 diabetes. Here we test whether a similar approach may reduce the risk of Breast Cancer and Endometrial Cancer.
Women at increased risk of breast and endometrial cancer by virtue of obesity (BMI >30kg/m2) +/- family history will be eligible. Participants will be randomised 2:1 to an immediate intervention group with 12 +/- 4 weeks of TDR with Optifast shakes (n=31) or a delayed intervention control group (n=16) with 12+/- 4 weeks of normal diet followed by 12 weeks of TDR. TDR will be followed by a 4 week food reintroduction and 8 month weight loss/maintenance phase. Vacuum assisted biopsy (VAB) of the breast and endometrial biopsy will be performed at baseline and during the final 4 weeks of TDR or normal diet. Tissue biopsies will be assessed for markers of cell division (Ki67) and other cancer risk biomarkers. Weight, body fat, fat free mass, waist and hip circumference will be measured every 3 months along with blood and urine tests, for markers of metabolism and cancer risk, and patient reported outcome measures. Mammograms will be performed at baseline and at the end of the study to assess changes in mammographic density.
The study will thus evaluate the feasibility of TDR in the prevention of breast and endometrial cancer and will inform the design of a larger randomised controlled trial, potentially against standard of care.Summary of results:
After 12-weeks on the low calorie diet replacement diet, the average weight loss was 9.9kg (9.6%) compared to the control group who had an average weight gain of 1.4kg (1.4%). The weight loss with the low-calorie diet was maintained until 9-months of the study. At this point, a small gain in weight was observed. At the end of the 12-month programme, the average weight loss was -8.4kg (-5.2%) compared to the starting weight. In the blood samples, levels of total cholesterol, blood fats, the hormone insulin and inflammation were reduced with weight loss. In women who lost at least 10% of their body weight, we saw lower stem cell activity in the breast, which could be a pathway that leads to cancer risk reduction.
This is the first study to assess the changes following weight loss from low calorie diet in both breast and womb tissues. The weight loss may lead to a reduction in breast cancer risk in women living with obesity, but larger studies are needed to understand the longer-term impact of the changes seen within this clinical trial. This study has shown researchers that the use of total diet replacement is acceptable to patients and with specialist dietitian support, can achieve significant weight loss. It has furthered our learning on the delivery of weight loss trials and is informing the design of future trials evaluating the use of weight loss for cancer prevention and treatment.
Summary of Results:
Thank you to study participants for your contribution to the Prevention of Breast and Endometrial Cancer using Total Diet Replacement (PROBE-TDR) study.The study was performed by researchers from the University of Manchester, sponsored by Manchester University NHS Foundation Trust.
The study was funded by a biomedical research council (BRC) grant [ref BRC-1215-20007].
The research proposal was reviewed by a group of women with lived experience of breast cancer, who gave their opinion on the nature of the study plan.
The study took place between September 2020 and February 2023.
Why was the research needed?
Breast cancer is the most common cancer in women and womb cancer is the fourth. Living with excess body weight is known to increase the risk of developing both of these cancers. Compared with a healthy weight woman, those who are three stone (20 kg) above a healthy weight have a 20% greater chance of developing breast cancer and three times the risk of developing womb cancer. Dietitian-supported low calorie diet replacement weight loss programmes can lead to weight loss and can help to manage Type-2 Diabetes. We wanted to see if a low calorie diet-replacement weight loss programme (850 kcal per day for 12 weeks) could be used to reduce breast and womb cancer risk markers in women after 12 weeks on the diet ultimately helping to reduce the risk of these cancers developing.What were the main questions studied?
The study explored the effects of weight loss after low calorie total diet replacement. The study looked at changes in the amount of body fat and muscle, blood markers and tissue markers in the breast and womb tissue in biopsies from women on the diet compared to a control group after 12 weeks on the diet. Also, how well women could maintain the weight loss over the rest of the year while trying to follow a healthy eating and physical activity weight control programme.What medical problems (adverse reactions) did the participants have?
The most common side effect following the breast biopsy was bruising. One participant had to return to hospital with bleeding after her breast biopsy. Following the womb biopsy, three participants reported pain which had stopped within three days. During the low calorie total diet replacement, the most common side effects were headache (65%), constipation (55%) and dizziness (48%). These symptoms were also present in the control group when following their usual diet and lifestyle, but at lower levels (headache (31%), constipation (19%) and dizziness (31%).What happened during the study?
Forty-seven women joined the study. Thirty were allocated to the immediate diet group and 17 to the delayed diet group. 29 women had completed 12 weeks of the low-calorie diet replacement and 16 completed the 12 week normal -diet control phase. A total of 37 participants (78%) completed the full 12 month weight loss programme.What were the results of the study?
After 12-weeks on the low calorie diet replacement diet, the average weight loss was 9.9kg (9.6%) compared to the control group who had an average weight gain of 1.4kg (1.4%). The weight loss with the low-calorie diet was maintained until 9-months of the study. At this point, a small gain in weight was observed. At the end of the 12-month programme, the average weight loss was -8.4kg (-5.2%) compared to the starting weight. In the blood samples, levels of total cholesterol, blood fats, the hormone insulin and inflammation were reduced with weight loss. In women who lost at least 10% of their body weight, we saw lower stem cell activity in the breast, which could be a pathway that leads to cancer risk reduction.This is the first study to assess the changes following weight loss from low calorie diet in both breast and womb tissues. The weight loss may lead to a reduction in breast cancer risk in women living with obesity, but larger studies are needed to understand the longer-term impact of the changes seen within this clinical trial. This study has shown researchers that the use of total diet replacement is acceptable to patients and with specialist dietitian support, can achieve significant weight loss. It has furthered our learning on the delivery of weight loss trials and is informing the design of future trials evaluating the use of weight loss for cancer prevention and treatment.
Where can I learn more about this study?
The results have been presented at Prevent Breast Cancer Conference, Manchester, October 2024. Further results are due to be published in 2025.REC name
North West - Preston Research Ethics Committee
REC reference
20/NW/0095
Date of REC Opinion
22 Apr 2020
REC opinion
Further Information Favourable Opinion