MBCC: What Affects Long-Term Breast Cancer Recurrence Risk?

Reasons for recurrence after treatment for early breast cancer are still not well understood. Lifestyle and other longer-term factors are likely at play, but the subject is difficult to study. The best advice for cancer patients is exercise and a healthy diet, for which there are currently guidelines from both the American Society of Clinical Oncology and the American Cancer Society.

Debu Tripathy, MD

On the last day of the 29th Annual Miami Breast Cancer Conference, Debu Tripathy, MD, USC Norris Comprehensive Cancer Center and Hospital in Los Angeles, California provided his perspective on the factors that may affect the long-term risk of breast cancer recurrence.

Dr. Tripathy pointed out that although complicated, there is a relationship between inflammation, metabolism, and growth pathways whereby levels of metabolic factors can influence the growth pathways that are involved in breast cancer. Diabetes, hypertension, and obesity are connected to a higher rate of recurrence and decreased survival in women with breast cancer.

"There is a connection between the growth factor pathways and estrogen pathways and metabolic pathways. We see that inflammation or high insulin levels (metabolic syndrome) can affect growth," he said.

Dr. Tripathy cited research that has shown that hyperinsulin signaling is associated with worse outcomes for breast cancer patients. The connection may be that the insulin receptor is related to the HER2/HER1 receptor-signaling through the insulin receptor can activate the downstream components of the HER2 pathway, Dr. Tripathy stated.

Higher levels of the insulin-like growth factor 1 (IGF-1), involved in metabolism, has been shown to be a risk factor for breast cancer through a pooled analysis of 17 prospective studies. IGF-1 stimulates mitosis and inhibits apoptosis, likely contributing to the proliferation of breast tumor cells.

People with a higher body-mass index tend to have higher insulin, which is related to higher breast cancer recurrence rates and higher estrogen levels, said Dr. Tripathy.

On the flip side, patients with a healthy lifestyle who engage in moderate exercise and eat high levels of fruits and vegetables and have a lower fat intake tend to have lower recurrence rates. This has been shown in several studies including one that shows reduced recurrence for both obese and non-obese women that followed the healthy regimen.

Dr. Tripathy mentioned that there is evidence that the oral antidiabetic drug metformin may reduce recurrence in diabetic women, and may also affect the outcomes of nondiabetic women. The ongoing trial, "A Phase III Randomized Trial of Metformin versus Placebo on Recurrence and Survival in Early  Breast Cancer," is currently addressing the effect of metformin on breast cancer recurrence. "This will be a very informative trial," said Dr. Tripathy.

Inflammation is also associated with lower risk of recurrence, as shown in studies of patients taking regular aspirin or a Cyclooxygenase (COX)-2 inhibitor. However, Dr. Tripathy highlighted that the data are from retrospective studies.

"Retrospective analysis now shows that beta-blockers are associated with lower risk of breast cancer recurrence," said Dr. Tripathy. The data so far is only in triple-negative breast cancer patients. Thus far, no prospective trials to study this effect are planned.

Dr. Tripathy believes that the link of body metabolism to breast cancer is the most compelling. "I routinely recommend that my patients embark on some form of physical activity and a heart-healthy diet."

A healthy lifestyle is important not only for breast cancer patients, but also can help to prevent other types of cancers as well as cardiovascular disease.