Our patients often ask whether lifestyle changes can help reduce their risk of breast cancer recurrence. While there is no shortage of opinion as to what to eat (or not eat), which exercise program is optimum, and how much alcohol is too much, hard evidence can be more difficult to find.

Many investigators are addressing these issues, and interesting data were presented at the most recent San Antonio Breast Cancer Symposium. The studies to date do not provide the definitive answers that many women seek – indeed, in some cases, they raise more questions – but they can help inform these discussions that are so important to our patients.

Soy and Breast Cancer

A number of recent publications, as well as a study presented in San Antonio by Dr. Masakazu Toi of Kyoto University, suggest that early-age intake of soy protein and isoflavones may contribute to lower breast cancer risk in Asian women. In addition, a recent publication from the Shanghai Breast Cancer Survival Study found that soy food intake was associated with a significant decrease in risk of death and recurrence in a cohort of 5,033 surgically treated breast cancer patients (JAMA 2009;302:2437-43).

Consequently, it is relatively perplexing that a biomarker study presented in San Antonio by Dr. Seema A. Khan of Northwestern University, Chicago, and colleagues failed to show a difference in Ki-67, a measure of breast epithelial cell proliferation that reflects cancer risk, following 6 months of soy isoflavone supplementation. There are several important considerations that might explain this. First, the Asian patients consume a variety of soy products as part of their normal diet, and not as a separately constructed soy isoflavone supplement. Second, intake occurs in the diet over years, rather than months. Lastly, it may be that the effect of soy is not well assessed by Ki-67 testing performed on random fine-needle aspirations that assess a small volume of cells.

So, what have we learned? Soy in the diet appears to reduce breast cancer risk in the long term, as well as the risk of recurrence and death. We don’t understand how this effect is mediated, and standard markers of proliferation may not be appropriate as measures. Supplements may have very different effects than does the daily dietary pattern. And, from this and additional data, it does not appear that dietary soy has any negative effects on breast cancer outcome.

Alcohol and Breast Cancer Recurrence

The data from an interesting prospective study by Marilyn L. Kwan, Ph.D., and her colleagues at Kaiser Permanente in Oakland, California, suggest that moderate alcohol intake is dangerous, and contributes to risk of relapse in women with early-stage breast cancer. The most curious finding was that the impact on breast cancer–specific survival and recurrence was seen in women who drank as little as one-half drink per day, but there was no impact on death from all causes, even in women who were moderate to heavy drinkers.

In addition, the negative effect of moderate alcohol intake on breast cancer recurrence was limited to postmenopausal and overweight women. It may be that outcome from cancers in younger women is more strongly affected by tumor biology than by lifestyle factors, and that lifelong drinking patterns also affect breast cancer recurrence risk. Underreporting of alcohol intake could have contributed to the effects seen with relatively low daily use.

In any case, a large, prospective study would help to define more clearly specific, modifiable lifestyle factors that affect risk of recurrence and survival after a breast cancer diagnosis, but may not be practical. At present, it is reasonable to counsel patients with a history of breast cancer to limit alcohol intake, maintain a healthy weight, and limit fat intake.

Distant Metastases and Obesity

A Danish registry trial confirmed an adverse effect of obesity on breast cancer mortality, concordant with data demonstrating an increased risk in breast cancer diagnosis as well as adverse cancer biology in women with significant postmenopausal weight gain. Indeed, this study also correlated obesity with adverse tumor biology and higher stage at diagnosis. In other studies, metabolic syndrome, obesity, and insulin resistance have been associated with poorer tumor biology, and the use of the antidiabetic agent metformin has been associated with decreased breast cancer incidence and perhaps improved outcome following diagnosis.

Although Dr. Martine Ewertz and her coauthors from the Danish Breast Cancer Cooperative Group suggested in San Antonio that inadequate dosing may account at least in part for their results, it is far more likely that biological factors are the critical component. The LISA (Lifestyle Intervention Study in Adjuvant Treatment of Early Breast Cancer) trial has enrolled more than 2,000 postmenopausal women with hormone receptor–positive, early-stage breast cancer in a program to evaluate the impact on recurrence of a 2-year, individualized, telephone-based lifestyle intervention focusing on weight management, compared with a mailed educational intervention. Follow-up is ongoing and results are expected in the near future. Metformin is also being tested as adjuvant therapy for breast cancer in MA.32, a large, phase III clinical trial from the National Cancer Institute of Canada (NCIC) in collaboration with the U.S. Breast Intergroup. NCIC MA.32 will randomize more than 3,500 women with early-stage breast cancer to receive 5 years of metformin or placebo, with a primary end point of disease-free survival.

What is the take-home message? As oncologists, we need to provide information to our patients about modifiable risk factors, and the encouragement to make improvements. This should include counseling regarding weight loss, along with standard adjuvant therapy.

For practitioners who care for women with breast cancer, advising patients about modifiable risk factors that may affect outcome should now be a routine part of survivorship planning.

Dr. Rugo is director of the breast oncology clinical trials program at the Helen Diller Family Comprehensive Cancer Center of the University of California, San Francisco. She has no disclosures to report related to these topics.

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