Other highlights from the March 21 JNCI

Increased Breast Cancer Risk Associated with Greater Fat Intake

Eating a high-fat diet may lead to an increased risk of invasive breast cancer in postmenopausal women.

Although environmental and animal studies have suggested that greater fat consumption may increase the likelihood of developing breast cancer, the results of epidemiologic studies have been inconclusive.

Anne Thiébaut, Ph.D., of the National Cancer Institute in Bethesda, Md., and colleagues asked 188,736 postmenopausal women how much and how often they ate certain foods to determine how fat intake affects breast cancer risk. Of the women surveyed, 3,501 developed invasive breast cancer.

The researchers found that doubling fat intake, from 20 percent to 40 percent, was associated with a 15 percent increase in breast cancer risk. The increase in risk was similar for all types of fat—saturated, monounsaturated and polyunsaturated.

"Meanwhile, results from this large prospective cohort with a wide intake range should contribute to the ongoing debate about the association between dietary fat and the risk of the breast cancer," the authors write.

In an accompanying editorial, Stephanie Smith-Warner, Ph.D., and Meir Stampfer, M.D., Dr.P.H., of the Harvard School of Public Health in Boston, propose that interventions that focus on controlling the amount of body fat, rather than fat intake, would be more effective in preventing breast cancer. "The modest associations that have been observed for dietary fat and breast cancer risk in observational studies and clinical trials stand in sharp contrast to the robust evidence for a strong link between [body fat] and the risk of postmenopausal breast cancer," the authors write.

Contact:

• Article: NCI Office of Media Relations, (301) 496-6641, ncipressofficers@mail.nih.gov
• Editorial: Meir Stampfer, Harvard School of Public Health, mstamphe@hsph.harvard.edu

Plant Compound in Diet Associated with Decreased Risk of Postmenopausal Breast Cancer

Postmenopausal women whose diet contains high amounts of lignans, estrogen-like chemical compounds found in plants, may have a reduced risk of breast cancer.

Lignans, which are found in flaxseed and a variety of fruits, vegetables and whole grains, belong to a family of compounds called phytoestrogens. Because of their hormone-like properties, phytoestrogens can bind to estrogen receptors, and some have suggested they may play a role in preventing breast cancer. Studies of Asian populations have found that women whose diets contain many foods made of soy, which are rich in another type of phytoestrogen, have a lower breast cancer risk.

Marina Touillaud, Ph.D. of the National Institute of Health and Medical Research in France, and colleagues administered a diet history questionnaire to 58,049 postmenopausal French women to examine the association between the consumption of four types of plant lignans and the risk of invasive breast cancer.

After a median follow-up of 7.7 years, 1,469 of the women were diagnosed with breast cancer. Among women with the highest total lignan intake, there were 376 cases of breast cancer per 100,000 person-years compared with 411 cases among women with the lowest intake—corresponding to a 17 percent relative decrease in the risk of breast cancer. The association was limited to breast cancers positive for estrogen and progesterone receptors.

"Although the possible role of plant foods in breast cancer prevention is still debated, increasing dietary lignan intake may be an interesting potential preventative approach. …In view of the epidemiologic results of this study, the recommendation that women should consume diets that consist largely of fruits, vegetables, and cereals—all foods rich in lignans—should continue," the authors write.

Contact: Dr.Francoise Clavel-Chapelon, National Institute of Health and Medical Research, +33 142114148, clavel@igr.fr

Outcome of Progression-Free Survival May Result in Biased Trial Results

Measurement of progression-free survival, a widely used endpoint in cancer clinical trials, has methodological flaws that can lead to biased estimates.

Katherine Panageas, Dr.P.H., of Memorial Sloan-Kettering Cancer Center in New York, and colleagues examined the use of progression-free survival (PFS) as an endpoint measurement in clinical trials.

PFS is measured as the time from start of treatment to the first measurement of cancer growth. Disease progression is typically measured by radiologic tests, such as x-rays, at scheduled intervals. Most often, researchers do not know when progression actually occurs, so they can only estimate that it happened sometime between the test that showed progression and the previous one.

Methodological problems can arise when researchers define the date of progression as the date on which it was first detected, even though progression most likely occurred prior to that day. The researchers compared a variety of surveillance intervals using a simulated population to demonstrate how the evaluation schedule can affect the estimation of PFS.

The researchers found that the outcome of the trial can be heavily influenced by the surveillance interval and that comparing the PFS times of two studies with different evaluation schedules can lead to erroneous conclusions.

"The decision to use PFS as a primary endpoint should be considered carefully in the design phase of the trial. It is our intention to make researchers aware that estimates of PFS are highly dependent on when they look for progression. The clinical research community can address this concern by adopting consistent strategies for interval evaluations in the design phase," the authors write.

Contact: Katherine Panageas, Memorial Sloan-Kettering Cancer Center, panageak@mskcc.org

Mutation to Mismatch Repair Gene Associated with Colorectal Cancer

Patients with a variant of a DNA repair gene, known as MLH1, may have an increased risk of a subtype of colorectal cancer.

Mismatch repair genes fix problems that arise during DNA replication when bases are incorrectly paired. Mutations in these repair genes are associated with increased risks of cancer.

Stavroula Raptis and Miralem Mrkonjic, graduate students at the University of Toronto, and colleagues analyzed two DNA mismatch repair genes, MLH1 and MSH2, in 1,359 colorectal cancer patients and 1,373 controls from Ontario and Newfoundland.

One particular variant in the MLH1 gene, -93G>A, was strongly associated with colorectal cancer. Patients with two copies of this version of the gene had a greater risk of colorectal cancer than patients with only one.

"Decreased levels of MLH1 expression associated with [MLH1 -93G>A] may lead to impaired cell cycle control, allowing cells to proceed with cell division before proper DNA repair can be accomplished. This impaired control would overwhelm the mismatch repair mechanism, leading to the accumulation of mutations," the authors write.

Contact: Nikki Luscombe, Mount Sinai Hospital, (416) 586-4800 ext. 2046, luscombe@mshri.ca

EMBARGOED FOR RELEASE: 20 MARCH 16:00 EST

Also in the March 21 JNCI:

• http://www.eurekalert.org/emb_releases/2007-03/jotn-ne031507.php
• http://www.eurekalert.org/emb_releases/2007-03/jotn-rp031507.php

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jnci.oxfordjournals.org/.