Dietary fat reduction in postmenopausal women with primary breast cancer: Phase III Women's Intervention Nutrition Study (WINS)
Reviewer: Christopher Dolinsky, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 18, 2005
Presenter: R.T. Chlebowski
Presenter's Affiliation: The WINS Investigators
Type of Session: Plenary
- Laboratory and retrospective research has suggested that dietary fat intake may be related to outcomes in breast cancer patients.
- The feasibility of interventions that decrease dietary fat intake in women has been demonstrated.
- Multiple studies have shown that overweight women have higher rates of breast cancer and poorer outcomes after treatment.
- The results of this trial have been heavily reported by the lay press.
Materials and Methods
- A multi-institution, phase III prospective trial randomized 2437 women with early stage resected breast cancer to two arms.
- Women were selected for this study if they reported that at least 20% of their daily calories were consumed from dietary fats.
- The experimental arm involved a series of interventions designed to decrease the patients dietary fat intake to less than 15% of their daily calories.
- This was accomplished through a series of 8 bi-weekly meetings with centrally trained nutritionists who counseled patients on lowering dietary fat intake.
- Compliance with the dietary modifications and measurement of dietary fat intake was assessed by a series of unsolicited phone calls (recalls) by trained personnel.
- 3 recalls were required for eligibility, and 2 recalls were performed each year during the study.
- Patients were encouraged to self monitor dietary fat, and group support session were available but not mandatory.
- The control arm saw nutritionists as well, but they were not counseled about dietary fat reduction.
- 40% of patients were randomized to the experimental arm, and 60% to the control arm.
- Primary endpoint was relapse free survival, and overall survival and disease free survival were secondary endpoints.
- Patients ranged in age from 48-79 years, and had histologically confirmed, resected breast cancers.
- Patients were not eligible with node negative tumors less than 1 cm, node positive tumors greater than 5 cm, or >10 positive nodes.
- Patients with ER + tumors received 5 years of tamoxifen and were allowed to receive chemotherapy, while patients with ER tumors were required to receive chemotherapy.
- Patients were stratified by nodal status, systemic adjuvant therapy, and sentinel node status.
- The trial was ended prematurely, during the 5th interim analysis, because of funding issues; however, the review board approved the current data analysis and presentation.
- Patients were well balanced in both arms according to most disease and demographic variables including: age, time from surgery, histologic subtype, nodal status, and hormone receptor status.
- The control arm contained more patients who received breast conservation therapy (p=0.004).
- Median follow-up was 60 months.
- The experimental arm was calculated to have a lower dietary fat intake than the control arm (20.3% of calories vs 29.2% of calories).
- The experimental arm had improved relapse free survival compared to the control arm (9.8% relapse vs 12.4% relapse, hazard ratio 0.76, p=0.034).
- The experimental arm had improved disease free survival compared to the control arm (hazard ratio 0.81, p=0.042)
- In an unplanned analysis, ER negative patients appeared to have a benefit to dietary fat reduction (hazard ratio 0.58, p=0.018) while ER positive patients did not (hazard ratio 0.85, p=NS).
- Overall survival was not significantly different between the 2 arms.
- The experimental arm had a significant decrease in weight compared to the control arm.
- By using an intensive program of multiple interventions, dietary fat intake can be decreased in a clinical trial setting.
- Life-style intervention involving dietary fat reduction may improve relapse free survival in breast cancer patients.
- There may be a bigger benefit to dietary fat reduction in patients with ER negative tumors.
- Further research in this area is warranted.
The authors present an interesting, large, multi-institution randomized trial. It appears that the intervention supplied in this investigation may improve outcomes for breast cancer patients. However, it is difficult to know exactly what aspect of the intervention produced these findings. The current literature shows a more robust relationship between body weight (as BMI) and breast cancer outcomes than dietary fat intake. Because the patients in the experimental arm had significantly decreased weights from the control arm, weight loss is a confounding variable in the analysis. It would be interesting to see a matched pair analysis of outcomes with patients in the experimental arm who had decreased dietary fat intake without significant weight loss compared to controls. One may also wonder if the substitution of other foods for dietary fats may have produced the benefits seen in this trial. Regardless, little debate exists in the medical community about the importance of low fat diets for preventing a variety of medical conditions. It is unlikely to become controversial to recommend low fat diets to overweight patients with breast cancer, even if this data is not the driving force behind that recommendation. Importantly, these data may help empower women with breast cancer diagnoses by suggesting that there are personal measures they can take to improve their outcomes after treatment.