Dietary Fat Reduction Improves Long-Term Survival in ER-negative Breast Cancers

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Reducing dietary fat intake appears to improve survival rates among women with certain types of breast cancer.
Reducing dietary fat intake appears to improve survival rates among women with certain types of breast cancer.

SAN ANTONIO—Despite disappointing results overall, reducing dietary fat intake appears to improve survival rates among women with certain types of breast cancer, according to a final, 20-year follow-up analysis of the randomized phase 3 multicenter Women's Intervention Nutrition Study (WINS) of dietary intervention as an adjuvant breast cancer therapy, presented at the 2014 San Antonio Breast Cancer Symposium.

“A lifestyle intervention targeting fat intake reduction associated with weight loss did not significantly increase overall survival of women with resected breast cancer receiving conventional cancer management,” concluded lead study author Rowan T. Chlebowski, MD, PhD, of the Los Angeles BioMedical Research Institute at the Harbor-UCLA Medical Center in Torrance, CA.

However, an exploratory analysis of study data suggested a “favorable lifestyle influence on survival in hormone receptor–negative subgroups and during active intervention,” Dr. Chlebowski noted. Dietary fat reduction interventions were associated with improved survival among women with ER-negative, and ER- and PR-negative, tumors.

Following preclinical and observational studies in the 1980s that suggested dietary fat intake may affect breast cancer treatment outcomes, such as differences in stage-specific breast cancer survival and diet between patients living in Japan and the United Kingdom, the WINS was initiated in 1994.

Eligibility criteria included dietary fat representing more than 20% of calories prior to the study.

Between 1994 and 2001, the researchers enrolled a total of 2,437 women diagnosed with early breast cancer at age 48 to 79 years. Participants were randomly assigned to receive primary surgery with or without radiotherapy, and systemic therapy (tamoxifen and chemotherapy for women with ER+ tumors; chemotherapy for women with ER-negative tumors), with (975 patients) or without (1,462 patients) dietary fat reduction.

The dietary fat intervention was designed to reduce fat intake while maintaining nutritional adequacy via eight biweekly individual counseling sessions by registered dieticians implementing a predetermined low-fat dietary plan, and subsequent follow-up discussions with the dieticians every 3 months.

At baseline, control-arm participants' mean fat consumption represented 29.2% of calories consumed, compared with 29.6% of calories from dietary fat among women in the intervention arm.

After 12 months of intervention, the mean fat intake among control-arm participants was unchanged (29.2% of calories), but the intervention-arm participants' dietary fat intake had dropped to 20.3% of calories (P<0.0001), Dr. Chlebowski reported.

That was accompanied by a net weight loss of 5 lbs (P<0.005; range 2.1 to 8 lbs lost). (Weight loss was calculated as mean weight lost by intervention-arm participants minus mean weight loss among control-arm participants.) A previous report had found that overall 5-year median relapse-free survival (RFS) was significantly longer among intervention-arm participants (P<0.0001).

However, at a median followup of 15 years, new mortality and survival rates were calculated using National Death Registry-confirmed mortality data. The death rate for control and dietary intervention-arm participants were 17% vs. 13.6% but that difference did not reach statistical significance (n=250 deaths vs. 133 deaths, respectively; overall survival [OS] hazard ratio [HR]: 0.94; 95% confidence interval [CI}: 0.76,1.2, not significant).

Importantly, however, among intervention-arm participants with ER-negative breast tumors (748 patients), survival rates diverged from control-group rates after year 5, such that cumulative HRs for death for this subgroup was significantly improved for years 1 through 10, 1 through 15 and 1 through 20 (P<0.046; cumulative 20-year HR: 0.64; 95% CI: 0.41,0.99).

Among women with ER- and PR-negative breast cancers (362 patients), dietary intervention was associated with significantly improved survival (median survival 14.0 years vs. 11.7 years; 20-year cumulative risk of death HR: 0.46; 95% CI: 0.27,0.78; P=0.006). For this subgroup, survival benefits were seen as soon as at the 3-year follow-up.

“Given emerging evidence, future lifestyle interventions should best target weight loss/maintenance and increased physical activity,” Dr. Chlebowski said.

The study was funded by the National Cancer Institute and the American Institute for Cancer Research.

References

  1. Chlebowski RT, Blackburn GL. S5-08. Presented at: San Antonio Breast Cancer Symposium 2014. Dec. 9-13, 2014; San Antonio, TX.
  2. Howlader N, Altekruse SF, Li CI, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014;106(5).
  3. Chlebowski RT, Blackburn GL, Thomson CA, et al. Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women's Intervention Nutrition Study. J Natl Cancer Inst. 2006;98:1767-1776.

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