Low-Fat Diet May Cut Risk of Breast Cancer Recurrence

Larry Schuster

May 24, 2005

May 24, 2005 (Orlando) — A low-fat diet may reduce breast cancer recurrence and increase relapse-free survival in postmenopausal women with early-stage breast cancer, researchers reported here at the American Society of Clinical Oncology 2005 Annual Meeting.

Overall, 9.8% of the women on the low-fat diet experienced tumor recurrence compared with 12.4% on a standard diet.

One patient subset that may derive particular benefit from a low-fat diet appears to be those with cancers that are estrogen-receptor (ER) negative, a marker for poorer prognosis, according to results of the prospective randomized phase 3 trial of about 2,500 women from 37 states. Researchers found the ER-negative women on a low-fat diet had a 42% lower risk of recurrence than women on a standard diet.

In his presentation, lead author Rowan T. Chlebowski, MD, PhD, at the Los Angeles Biomedical Research Institute, Torrance, California, at Harbor-University of California, Los Angeles, Medical Center, said analysis of ER status involved only a subset of 478 patients, was not preplanned, and therefore should be only considered hypothesis generating.

The results of the study, funded by the National Cancer Institute, were compiled after a five-year median follow-up period from the Women's Intervention Nutrition Study (WINS).

The eligible women were at least 48 to 79 years of age with histologically confirmed resected unilateral invasive breast cancer. Lymph node evaluation and acceptable adjuvant systemic treatment were required. Dietary fat intake had to exceed 20% of calories at baseline, and the woman had to be willing to accept either dietary plan at randomization.

Exclusion criteria included preoperative chemotherapy, previous neoplasm, and women with tumors less than 1 cm with negative nodes, tumors more than 5 cm with positive nodes, or those with 10 or more positive nodes.

The patients had baseline dietary fat intake of more than 20% of calories. They were randomized within 365 days from primary surgery to a dietary intervention designed to reduce fat intake or the controlled condition. Recruitment occurred between 1994 and January 2001.

The primary study endpoint was relapse-free survival defined as time from randomization to breast cancer recurrence, including local, regional, distant, and ipsilateral breast recurrence, as well as new contralateral breast tumor development. A secondary endpoint was overall survival.

Women with ER-positive disease received 20 mg of tamoxifen per day for five years with the option of receiving one of the WINS-approved chemotherapy regimens as well. Women with ER-negative disease were required to receive one of the approved chemotherapy regimens.

The dietary intervention goal was to reduce dietary fat intake, maintaining nutritional adequacy with a target of 15% calories from fat. Weight loss was not an intervention goal, and women were not counseled on weight reduction issues.

Dietary assessment was performed with unannounced, 24-hour telephone recalls by trained interviewers. These data were entered into the nutrition data system software at a nutrition-coordinating center. Three recalls were collected for two weeks for eligibility and then two recalls annually while enrolled in the study.

Women in the low-fat diet group were given a fat-gram goal by centrally trained, registered dieticians implementing a previously developed low-fat eating plan. Eight biweekly individual counseling sessions initiated the intervention, and subsequent nutritionist contacts were scheduled every three months.

Ultimately, 975 women were randomized to a dietary intervention, and 1,462 were in the control group. The two groups were balanced with regard to most baseline characteristics; age, time from surgery to study entry, nodal status, and histologic type were closely comparable.

In both groups, patients received similar systemic therapy. Slightly less than half the women received chemotherapy with anthracycline-containing regimens. Few patients received taxanes.

After one year, daily dietary fat-gram intake was slightly reduced in the control group but was reduced to a significantly greater extent in the dietary intervention group. A difference in daily fat-gram intake was maintained through five years and beyond, although study subjects did not achieve the 15% dietary fat-intake goal. Mean intake was reduced from 29% to 20%.

Although weight loss was not an intervention target, women assigned to the low-fat diet group had modest weight loss (mean, 2 kg). Women in the control group, however, gained weight. The weight differences were statistically significant and support dietary change having occurred in the low-fat diet group.

Dr. Chlebowski said, "Based on these findings, we conclude that dietary fat intake can be reduced in breast cancer patients participating in a multicenter clinical trial. A lifestyle intervention resulting in dietary fat reduction may increase relapse-free survival in a population of mostly postmenopausal breast cancer patients. Exploratory analysis suggests a greater dietary effect in breast cancer patients with ER-negative disease.

One of the key questions that emerged from the study is whether the result, if confirmed, was a result of dietary fat or modest weight loss.

Asked if a change in dietary fat could be responsible, independent of weight loss, Nagi Kumar, PhD, director of the Department of Nutrition at the Moffitt Cancer Center, University of South Florida, Tampa, told Medscape, "It could not be." Weight gain has a compelling scientific history and mechanism when it comes to cancer compared with dietary fat, Dr. Kumar said.

Weight gain is common in these patients and may be a result of hypothyroidism or subclinical hypothyrodism, Dr. Kumar questions in a recent article in which she reports a 25% incidence of hypothyroidism among 196 treated breast cancer patients compared with 4% to 6% in the general population. Based on these findings, Dr. Kumar speculates about whether the hypothyroidism might have an impact on future health of the breasts, as well as a possible relationship to weight gain and lethargy often seen in these patients.

Commenting on the study immediately following Dr. Chlebowski's talk, Eric Winer, MD, director of the Breast Oncology Center at Dana-Farber Cancer Institute, Boston, Massachusetts, noted there is extensive literature showing a statistically significant association between increased weight and tumor recurrence or death after a diagnosis of breast cancer.

Dr. Winer said, however, that "the relationship of dietary fat to breast cancer risk and prognosis is somewhat more complex and less clear cut. There is a well-known association between fat intake by geographic region and breast cancer risk." But, Dr. Winer said, "Cohort studies, however, had failed to demonstrate consistent relationships between dietary fat intake and breast cancer risk."

Dr. Winer said, "The bottom line is that the evidence is far less compelling for an association of dietary fat intake in breast cancer outcome than for either weight or body mass index.

Noting the 4 lbs (2 kg) or 3% mean body weight reduction in the study, Dr. Winer said, "This decrease in body weight confounds the ability to assess the primary objective, that is, the impact of dietary fat reduction. But, it may also be partially or entirely responsible for the treatment effect."

"I think these results are tantalizing. The magnitude of the effect that was seen here is similar to that observed with many widely accepted interventions. Despite the suggestion of benefit, the study is not definitive. Further follow-up will be needed, and given the borderline statistical significance witha P value that is hovering around .05 and the absence of a confirmatory trial, we cannot draw firm conclusions from this study."

In a telephone interview with Medscape, Dr. Chlebowski said he recognizes this is a preliminary trial, but is one more reason to consider the benefits of diet, especially for motivated patients who ask what they can do. In the course of the study, patients lost some weight and ate more fruits and vegetables.

In this trial, the results, according to Dr. Chlebowski, are still not yet strong enough to offer patients a "guilt statement" by telling them that they will benefit if they start a low-fat diet or will do worse if they do not.

Still, "It is a first signal in a specific cancer that there might be benefit from making some changes to one's diet."

ASCO 2005 Annual Meeting: Abstract 10. Presented May 16, 2005.

Reviewed by Jacqueline A. Hart

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