To round up this year’s report from San Antonio, I want to tell you about some other studies that I felt had particularly interesting findings. Weight Loss to Reduce Risk of Recurrence Researchers reported updated findings from the Women’s Intervention Nutrition Study, a randomized study started in 1987 that looked at whether reducing dietary fat would reduce the risk of a breast cancer recurrence in postmenopausal women who had been treated with surgery and adjuvant therapy for invasive breast cancer. The study included 2,437 women between the ages of 48 and 79. For five years, half of the women maintained their regular diet and half maintained a strict low fat diet—with less than 15% of their calories coming from fat. The goal was not to reduce weight, but to reduce fat intake. (We now know though that weight loss probably matters more than dietary fat in reducing the risk of recurrence and improving long-term outcomes.) By year three, the women in the low-fat group had lost an average of about 6 pounds, decreasing their body-mass index (BMI) by 1. Although the study ended in 2004, the investigators continued to follow the women. After 20 years of follow up, the data show that 13.6% of the women in the low-fat group have died compared with 17% of the women who did not change their diet—a difference that was not statistically significant. However, when the researchers looked at the women by tumor type, they found that the low-fat diet increased survival by about two years in women who had hormone-receptor negative (ER- and/or PR-negative) or triple negative (ER-, PR- and HER2-negative) tumors. Even though the benefit was only statistically significant in that group, I would still recommend that women try to maintain or lose weight (if necessary) after a breast cancer diagnosis through diet and exercise for overall health—not only breast health. Watchful Waiting for DCIS? We know that there are many women who are diagnosed with ductal carcinoma in situ (DCIS) who will not go on to develop invasive breast cancer—but we don’t yet have a way to determine who those women are. Genomic Health developed the Oncotype DX test that is used to help determine if a woman with an early-stage breast cancer will do as well with hormone therapy alone as with hormone therapy and chemotherapy. Then, they developed a similar test for women with DCIS that could identify which women needed radiation after surgery. They first confirmed the test worked by studying tissue samples from a large prospective multi-center study that looked at recurrence rates in women with DCIS who did—or did not—receive radiation after surgery. Findings from a new study that looked at how well the test would predict recurrence in the real world were presented at San Antonio. To do the study, the researchers applied the Genomic Health DCIS test to tissue samples taken from 571women in Canada whose DCIS had been treated with a lumpectomy and removed with clean margins. These women were treated 10 years ago, and the researchers tracked down what had happened to them since their DCIS was removed. Overall, the recurrence rate after 10 years was 19.2%—in other words, 80% of the women were fine 10 years later. If a woman had a low score on the DCIS test, her risk of recurrence was 12.7%; if she had an intermediate score, her recurrence risk was 27.8%, and if she had a high score, her risk of recurrence was 33%. The Genomic Health test accurately predicted the 100 recurrences—57 invasive and 44 DCIS. For the women with the low recurrence score, we could probably do “watchful waiting”—as we do with some prostate cancers—rather than recommending immediate surgery. Right now, though, unlike with prostate cancer, we don’t have any markers to watch. At Dr. Susan Love Foundation for Breast Cancer Research, we are working on a project to map the extent of DCIS within a breast so that someday, we can consider eliminating surgery for DCIS altogether. Stay tuned! Tumor as OrganismDr.Joan Brugge, the chair of the department of cell biology at Harvard Medical School, was this year’s recipient of the Susan G. Komen Brinker Basic Science Award. She was described as a promiscuous collaborator, suggesting she will collaborate with any and all researchers with good ideas—a title I would like to have myself! At the meeting, the award winner always gives a talk, and Dr. Brugge’s was quite provocative, in that it explored the idea of a tumor as an organism. I found this to be the most interesting talk at the meeting. Why think of a tumor as an organism? Well, as Dr. Brugge noted, a tumor is comprised of an enormous variety of cancer cells as well as a large cast of supporting cells and tissues such as blood cells, nerves, lymphatics, immune cells, fibrous tissue, and fat cells. In other words, it is not just one large group of homogeneous cells. This means that the cells removed on a tumor biopsy may—or may not—be similar to most of the cells that make up the tumor. Targeted treatments are decided based on the mutations the tumor already has. But as we have learned at this conference, tumors are ever-changing organisms that are continually developing new mutations. And they have the ability to convert the supporting cells to their own use. The tumors really are like homegrown terrorists that are willing to co-opt whatever resources are available to enable them to accomplish their goals to take over a body. From a treatment perspective, we need to think about how to use chemotherapy and targeted therapies within the context of treating an ever-mutating tumor. Will we need to customize therapies for primary and recurrent, metastatic cancers based on specific genetic alterations that are present in the tumor at each point in time? And even if these were feasible, we also have to account for the fact that the cancer cells can switch their phenotype— or how they appear—depending on the microenvironment or neighborhood they are in. This is also an important element in how the cells behave. But Dr. Brugge suggested that this might not be enough. We need to understand the tumor ecosystem so that we can eliminate it and prevent the adaptation and expansion of resistant cells—while causing minimal harm to normal cells. The analogy is to destroy or convert a terrorist state rather than focus on individual terrorists one by one. She also noted that while the tumor ecosystem is robust and able to adapt to new therapies and environments, “there [also] is a limit to the number of insults that the tumor ecosystem can withstand.” This means we need to develop treatments that push the ecosystem to a point beyond its ability to adapt. Otherwise, it will become resistant. To do this, she said, “We need to stop trying to kill cells one by one and target the tumor ecosystem by identifying the optimal immunotherapies for different classes of breast cancer, establishing how to integrate them with standard of care and emerging therapies, and by targeting multiple cellular vulnerabilities in parallel to prevent adaptation.” Listening to Dr. Brugge made me think about how lifestyle (weight loss and exercise), inflammation, and hormones affect a tumor’s ecosystem, and how they help create an environment that will—or will not— support a tumor’s development. It also made me think about what we can do to create an environment that will not let a cancer develop in the first place! Liquid Biopsies: The Next Big Thing? If we are going to treat the tumor as an ecosystem, then we need to find ways to monitor new mutations that develop in metastases, since they may not match the primary tumor. The hot new approach is being termed “liquid biopsies”—which is really just a fancy term for a blood test that looks for either circulating tumors cells (CTC’s) or circulating free DNA. Under normal conditions, we often have free DNA circulating in our blood. Now, with what scientists call “next-generation sequencing,” we have a technology that allows individual cells and even strands of DNA to be captured and identified, allowing us to get a sense of what is being shed into the blood. We still have not confirmed that CTC’s or even free DNA will match metastases, but that is certainly the hope. If it can be shown to be true, then women with recurrences will be able to be monitored through a blood test and treated with therapies selected based on the mutations currently present in the tumor. This would be a wonderful development—but we are not there yet. Love Research Army I would be remiss if I did not tell you that one of my personal highlights of this year’s meeting was when our Love Research Army made it to the podium. The researcher, Andrea Pusic, presented her work on patient’s experiences after various breast reconstruction techniques. In her presentation, she mentioned Dunya Atisha’s published work, which recruited study participants through Dr. Susan Love Foundation for Breast Cancer Research Love Research Army. The study, published in the December 2014 Annals of Surgical Oncology, presented findings from a questionnaire about breast reconstruction completed by more than 7,619 women. The researchers found that the women who had reconstruction using their own tissue reported the highest breast satisfaction; women who had a mastectomy without reconstruction reported the lowest satisfaction. The Love Research Army was mentioned in both the paper and her slide. We are grateful to all our Love Research Army volunteers who register, participate, and share information about upcoming studies looking for participants. You are truly a valuable resource to the breast cancer research community!
