An update on your support of the Kaplan Cancer Research Fund Swedish Cancer Institute

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1 An update on your support of the Swedish Cancer Institute At Swedish, we re committed to offering our patients the newest, most innovative cancer treatment available. Through your support of the at the Swedish Cancer Institute, you re helping us make this vision a reality. Last year alone, supporters like you gave more than $1.3 million to research to SCI to help us prevent, treat and ultimately eliminate cancer. I m pleased to share this update on the pioneering research your support helps make possible. Over the past year, the Kaplan Fund sponsored several exciting research projects with the potential to yield better, more effective treatments for cancer. Together, we re bringing hope to our patients and their families, thank you. Developing treatments for patients with rare nerve sheath tumors In 2013, we first described the treatment of a patient with a malignant peripheral nerve sheath tumor (MPSNT), a rare form of cancer in the cells that cover nerves. This particular patient had a mutation in the BRAF gene (a gene that makes a protein called B-Raf) that s commonly associated with melanoma. We treated this patient with a BRAF inhibitor drug (a therapy that blocks cancer cells from growing) commonly used to treat melanoma, and the results were very encouraging. Henry G. Kaplan, M.D., medical oncologist and head of Kaplan Cancer Research Fund at the Swedish Cancer Institute Over the past year, our team has continued to work with Boston-based Foundation Medicine, a prominent genome evolution company, on a study to measure the incidence of BRAF mutations in patients with MPSNTs. To do this, we combined data from patients receiving their care at SCI with those evaluated at Foundation Medicine. We believe this will be the largest series of such patients ever reported, and we re hoping our work leads to clinical trials focused on inhibitor drugs for patients with MPSNTs. As part of this research we also described for the first time a new unique BRAF mutation that we ve found in a number of different tumor types. What excites us about this is that there are now drugs available that could inhibit the activity of this mutation, and one patient has shown a response already.

2 Swedish Cancer Institute Studies to treat breast cancer and prevent its recurrence We continue to be very active in studies related to breast cancer. Our success in this area is largely due to the Swedish Breast Registry. This robust database tracks detailed information on breast cancer patients spanning diagnosis and treatment, collecting 80 more data points per patient than a standard, nationally-mandated registry. This data is also longitudinal, meaning that it follows patients over the course of their lifetime, not just during their treatment. Thanks to supporters like you, we re able to maintain this invaluable resource by ensuring qualified staff are available to input new data and extract information designed to improve patient care and outcomes. The Swedish Breast Registry plays a central role in many of our research efforts, such as our ongoing project to compare the impact of early detection by mammography versus improvements in treatment. This is an extremely important issue, as there s a continuing international debate on who should have mammograms and how often they should have them. Over the past two decades there s been a considerable decrease in the breast cancer mortality rate, and it s difficult to determine what s played a larger role in this success mammography or better treatments. For some time now we ve explored the impact of mammography on the decreasing mortality rate. Now we re devoting considerable effort to examining how much new breast cancer treatments improve the health and outcomes for women with this disease. Over the past two years we ve published a number of studies on this topic, some of which looked at the general population and others that focused specifically on the elderly. We were recently approached by the Breast Cancer Research Foundation to study the course of metastatic breast cancer in our patients here at Swedish. Metastatic cancer is a cancer that s spread from the part of the body where it started (the primary site) to other parts of the body. Most breast cancer databases contain little information about this connection, but we re hopeful that the Swedish Breast Registry will allow us to explore it in greater depth. We also continue to participate in various clinical trials for breast cancer, including the highly innovative I-SPY 2 trial. This national research study brings new drug therapies to patients with breast cancer who urgently need them. Each participant is prescribed a series of medications before undergoing surgery. Their results are then analyzed throughout the course of the study, and advanced statistical methods are used to determine the likelihood that a given drug will help a particular patient. Results from early trial participants guide treatment for later participants, so researchers can determine quickly on whether a treatment is worth pursuing or not. When evidence indicates a high

3 Swedish Cancer Institute probability of success, the drug graduates to final-phase testing. So far, two of the drugs we ve introduced, veliparib and neratinib, have shown very promising results for patients. These results were published in the July 7, 2016 issue of The New England Journal of Medicine. We also continue to be very active in trials for vaccines that could prevent recurrence for breast cancer survivors. Kristine J. Rinn, M.D., medical oncologist at SCI, and I are still participating in trials related to NeuVax, a peptide vaccine aimed at preventing or delaying the recurrence of breast cancer in survivors who achieve remission after standard cancer treatment (e.g., surgery, radiation and chemotherapy). Our first study in this area, called Present, is complete and those results will soon be published. The data from the Present study has not shown NeuVax to be significantly beneficial for patients. However, our follow-up study to explore the effectiveness of NeuVax combined with Herceptin (also known as trastuzumab) is going well and enrolling many patients here and nationwide. Even though the Present study had limited success, there are reasons to believe that NeuVax may be synergistic with Herceptin, so we re hopeful that this study will yield more promising results. This past year, our in-house research group broadened to include the efforts of Erin D. Ellis, Donations to the help sustain vital research to improve patient care and outcomes. M.D., from medical oncology and Astrid D. Morris, M.D., from radiation oncology. Together, we ve explored the appropriate indications for performing radiation on the lymph nodes under the arm (called the axillary nodes) after breast surgery. With improvements in medical treatments for breast cancer, many physicians are now questioning how aggressively the axillary nodes should be treated with radiation and/or surgery. We ll be presenting two papers on this topic at the San Antonio Breast Cancer Symposium in December. Using stem cells to fight breast cancer Our team continues to work with Charles Cobbs, M.D., Parvinder Hothi, Ph.D., and the research group at the Swedish Neuroscience

4 Swedish Cancer Institute Institute (SNI) to study malignant stem cells in breast cancer. Stem cells are the cells from which all other cells eventually grow and differentiate into the various organs of our bodies. It s well understood that there are malignant stem cells, the mother cells that feed the continued growth of cancers. Some theories suggest that our inability to cure most cancers is the result of their stem cells continuing to thrive and becoming resistant to the drugs that kill their offspring. Dr. Cobbs group has been successful in growing the stem cells that feed a particularly virulent and deadly form of brain tumor, and are testing these cells to determine what kinds of therapies may eliminate them. This year your generous donations helped to advance our collaboration with SNI. We re excited to report that this project is now up and running, and we ve successfully grown breast cancer stem cells using samples from three patients. Many of our breast cancer surgeons at Swedish, particularly Karen J. Hendershott, M.D., have shown a great interest in this work, as it has the potential to dramatically improve how breast cancer is treated. This is a long-term project, but we re excited about the progress we ve made so far. Our ultimate goal is to develop treatments to attack the original malignant cells rather than their offspring, as this could help eradicate drug-resistant clones of cancer. Researching innovative therapies for blood cancers In the area of blood cancers, our team continues to study the development of leukemia and other bone marrow disorders in patients who have received chemotherapy and radiation. Unfortunately, certain cancer treatments can cause some patients to develop leukemia or bone marrow disorders in addition to their primary cancer. This past August we published a paper on this topic in Leukemia Research, an esteemed medical journal read by health care professionals worldwide. Thank you! Thank you for your thoughtful support of the at SCI. Your generosity allows us to remain at the forefront of cancer research and to bring treatments with the best possible outcomes to our patients. We re honored to count you as a partner in this important work, thank you! You can learn more about Dr. Kaplan s research publications at Swedishfoundation.org/kaplan. Thank you for your extraordinary caring.

5 Swedish Cancer Institute Research Initiatives Expand the Frontiers of Cancer Research Evaluating Scientific Wellness in breast cancer survivors Each year, approximately 250,000 women in the United States are diagnosed with invasive breast cancer, while an additional 60,000 women are diagnosed with noninvasive breast cancer. While these numbers are daunting, improvements in breast cancer detection and treatment are helping more women survive this disease. As the number of breast cancer survivors continues to grow, the quality of survivorship for women cured of cancer and for those whose disease remains active is increasingly important. Thanks to projects like The Cancer Genome Atlas and The Human Genome Project, we have a much better understanding of human biology overall and how cancer can affect each person differently. This increase in knowledge and understanding has led physicians and researchers at SCI and our partners at the Institute for Systems Biology (an affiliate of Providence Health & Services, as is Swedish) to develop an approach called Scientific Wellness. This new methodology uses molecular biology to develop expert medical tools to assess and improve wellness among breast cancer survivors. Dr. Kaplan is part of a team that will use Scientific Wellness to explore, and ultimately improve, quality of life for breast cancer survivors. SCI will recruit 100 women with newly diagnosed breast cancer and monitor them with scientific wellness tools before, during and for at least two years following treatment. This monitoring will track various aspects of each woman s unique biologic structure (known as biomarkers), including their hormonal levels, organ and physiologic systems and an analysis of gene mutations related to their cancer. We ll also study the common side effects of treatment including neuro-cognition issues, fatigue, joint pain and gastrointestinal inflammation. Through this study, SCI researchers hope to identify biomarkers that help us better understand how different women react to their cancer and to specific treatments. Similarly, the research team hopes to develop a clearer picture of how specific cancers will react to specific treatments. Both of these points are especially important in the context of increased survivor ship, as they have the potential to help women live healthier lives past treatment.

6 Swedish Cancer Institute Research Initiatives Expand the Frontiers of Cancer Research continued... New Clinical Trials Unit at Swedish First Hill opened in March 2016 Your support of the Kaplan Fund helps advance critical research to improve the health and well-being of patients with cancer. Thanks to you, SCI has one of the most established clinical cancer research programs in the region. In addition to Dr. Kaplan s research activities, SCI is currently participating in 170 clinical trials of new cancer therapies, including many personalized therapy trials. This past March, our research program expanded with the opening of the Robert and Jean Reid Family Innovative Therapeutics & Research Unit (ITU), which was generously funded in part by philanthropic contributions. The Reid ITU is an early-phase clinical trials unit focused on investigational therapies that are driven by SCI s Personalized Medicine Program, which helps match our patients with therapies and investigate key questions about personalized treatment. This state-of-the-art center contains a specialized pharmacy, a supportive care space for our patients and their families, and new treatment rooms that allow our patients to participate in any available clinical trial. SCI s unique model delivers the best of both worlds, bringing together the patient care of a top-ranked medical center and the lifesaving research often found in large university-affiliated hospitals. Because of supporters like you, patients have access to the latest clinical trials and research to help find the best treatments for their cancer. To learn more about these initiatives or to continue your investment in the, please contact: Lauren Moore, CFRE Philanthropy Director, Swedish Cancer Institute or Lauren.Moore@swedish.org 747 Broadway Seattle, WA Foundation@swedish.org Swedishfoundation.org