Sandra Yin

September 23, 2011

September 23, 2011 (Washington, DC) — Stress is associated with the aggressiveness of breast cancer, according to a study presented here at the Fourth American Association for Cancer Research Conference on the Science of Cancer Health Disparities.

The cross-sectional study looked at the potential relation between stress and tumor aggressiveness in the human population. Researchers found that patients with greater levels of fear, anxiety, or social isolation were more likely to have aggressive tumors.

"What we found, very generally, was that there was an association," Garth Rauscher, PhD, associate professor of epidemiology at the School of Public Health at University of Illinois at Chicago, told Medscape Medical News. "Patients who reported greater levels of stress were more likely to have high-grade, more aggressive tumors. They were also more likely to have tumors that lack hormone receptors."

During an interview 2 to 3 months after diagnosis, black and Hispanic patients with breast cancer reported higher levels of stress than white patients, Dr. Rauscher said.

The study looked at 989 patients recently diagnosed breast cancer: 397 non-Hispanic whites, 411 non-Hispanic blacks, and 181 Hispanics.

The researchers used 3 different stress scales, combined into a single measure of psychosocial stress. They defined breast cancer aggressiveness in terms of hormone (estrogen and progesterone) receptor-negative tumors and tumors with high histologic grades.

Earlier studies looked at stress and the incidence of breast cancer on survival and recurrence, but this is the first population-based study to look at the potential role of stress in tumor aggressiveness, Dr. Rauscher said. He noted that studies have shown that the incidence of breast cancer rises among socially isolated rat mothers.

Anil Sood, MD, professor and director of the Blanton-Davis Ovarian Cancer Research Program in the Departments of Gynecologic Oncology and Cancer Biology at the University of Texas M.D. Anderson Cancer Center in Houston, told Medscape Medical News that he found the study interesting because it seems to support the concept that stress can influence cancer biology. However, he also noted that causality is difficult to determine, given the constraints of the study design.

"For causality, one would have to see a strong relationship that can be manipulated by an intervention that would reverse the harmful factor," he said. Because Dr. Rauscher's study is correlative, it is difficult to establish causality or directionality, Dr. Sood explained.

Dr. Rauscher acknowledged the study's limitations. "This is not in any way a definitive study," he said, noting that it is still a work in progress. "It's purely exploratory."

A major limitation of the study, he said, is that the stress levels are reported after diagnosis and during treatment. As a result, it is not clear what is driving the association between stress and tumor aggressiveness. It is completely conceivable that somebody with a more aggressive tumor might subsequently report higher levels of stress. A woman with a more aggressive tumor who is aware of the more worrisome diagnosis would likely feel more stress. The more aggressive treatment someone with an aggressive tumor faces might also influence the stress she feels.

It is possible the direction of the causal relation is the opposite of what one might assume, Dr. Rauscher said. Although the researchers were interested in the way stress influences tumor aggressiveness, it is possible they were measuring the way tumor aggression influences stress. "There is no way in this study to disentangle them," Dr. Rauscher said.

A major assumption of the analysis was that patients who reported greater psychosocial stress at an interview, which was 2 to 3 months after diagnosis, would have also reported relatively greater psychosocial stress had they been interviewed before diagnosis.

Dr. Rauscher noted that although the association between stress and tumor aggression shrank a bit after adjustment for variables such as stage of diagnosis and status of treatment at the time of the interview, such variables don't seem to account for the relations they saw.

According to Dr. Rauscher, the potential role of DNA methylation, as it relates to race and ethnicity and tumor aggression, is worth exploring.

He also said it would make sense to go back and revisit some of the earlier cohort studies that used a variety of stress measures, and look to see if they have medical records and pathology data on these tumors. It might help to see if researchers can identify which ones were more adverse and less aggressive and tease out the role of stress. "It's very hard to study," he said. "How do you even measure stress?"

Drs. Rauscher and Dr. Sood have disclosed no relevant financial relationships.

Fourth American Association for Cancer Research (AACR) Conference on the Science of Cancer Health Disparities (SCHD): Abstract A91. Presented September 19, 2011.

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