Published June 6, 2014 By Dr. Susan Love

Over the past few years, we’ve seen a number of studies that have suggested a link between weight and postmenopausal cancer.  So, intriguing findings from one study presented at ASCO took many of us by surprise. The general consensus has been that weight increases breast cancer risk, particularly in postmenopausal women, because fat uses the aromatase enzyme to make estrogen. To explore this idea further, Hongchao Pan used information about body-mass index (BMI) that was collected from 80,000 women who had taken part in 70 clinical trials conducted by the Early Breast Cancer Trialists’ Collaborative Group to look at the relationship between weight and breast cancer prognosis. Pan’s study found that obesity specifically increased the risk of death among women who are diagnosed with ER-positive breast cancer before menopause. He found no relationship between obesity and outcome in pre- or postmenopausal women with ER-negative breast cancer or in postmenopausal women with ER-positive tumors. Specifically, the study found that among the 20,000 premenopausal women with ER-positive breast cancer who had taken part in the clinical trials, those who were obese (defined as having a BMI greater than 30) were 34% more likely to die of breast cancer than were those who were normal weight. Another way to put it: After 10 years, premenopausal women who were ER positive and obese had a 21.5% risk of dying of breast cancer compared to the 16.6% risk of those who were normal weight. This disturbing news was accompanied by two studies that looked at weight loss in breast cancer survivors showing benefits in intermediate markers such as sex hormone levels and decreased inflammatory markers. In one of the studies, called SHAPE-2,the researchers found that postmenopausal women who were active were 10% to 25% less likely to get breast cancer than were inactive women. In the second study, called LEAN the researchers found that women who lost weight while taking part in a 6-month, 11-session counseling program were more likely to have inflammatory and metabolic biomarkers that have been associated with breast cancer survival. This year, we also learned more about how the immune system responds to a tumor.  I don’t mean immunotherapies, the new drugs that I discussed after the AACR meeting.This research is about whether indicators that the body’s immune system is responding to the tumor can predict whether a tumor will respond to a specific type of treatment, and what the prognosis might be. Traditionally, breast cancer has not been thought to be a tumor, like melanoma, that is responsive to immune changes. But Edith Perez presented data from a study that identified some measures of the body’s immune response that may be linked to outcomes in women with HER2-positive or triple negative tumors. In this study, Perez and her colleagues identified the women who been enrolled in a previous Mayo Clinic trial and had had the best response to the HER2-targeted therapy trastuzumab (Herceptin). They then analyzed samples of these women’s tumors. This analysis identified 14 genes in the tumor that correlated with a good response to Herceptin. Women whose tumors had at least nine of these 14 genes responded well to Herceptin. Women whose tumors had less than nine did not. These findings need to be validated in larger studies before a test that looks for these genes is used to help select treatment options. But what I find intriguing is that most of the genes were related to the immune system. This is only one of the studies that suggested that the immune system plays an important role in how a tumor responds to Herceptin. Another randomized clinical trial of Herceptin (FinHER) showed that tumors that had a lot of associated lymphocytes (immune white blood cells) responded better to chemotherapy and Herceptin than chemotherapy alone. And yet another, which looked at whether tumor infiltrating lymphocytes (TILs) could predict benefit from carboplatin in triple negative breast cancer, found that  immune inhibitors were linked to remission rates. Carsten Denkert, who presented the findings about the TILs, suggested this probably reflects that the immune system has been activated. In addition, similar studies were presented in the final breast cancer session regarding triple negative breast cancer, with indications that tumors that show an immune response to treatment do better. I may have left ASCO exhausted but I also left convinced—as I was after the AACR meeting—that the immune response and drugs that can tweak it are going to be the wave of the future in breast cancer and other cancer treatments.

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