Breast Cancer Advances

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1 Winter 2011 Breast Cancer Advances Page 2 Page 4 Page 5 Page 6 Page 7 Page 9 Advancement of Individualized, Personalized Surgery and Local Therapy for Breast Cancer to Minimize Treatment The Breast Surgical Services group specializes in minimally invasive surgical approaches, including nipple-sparing mastectomy, perforator flap reconstructive surgery and image-guided surgery, as well as novel pre-operative medical treatment. New Radiation Techniques Reduce Risk of Organ and Tissue Injury and Offer Shorter Treatment Courses Breast Oncology Center radiation oncologists are employing innovative techniques that reduce injury to vital organs and offer shorter radiation courses for patients with early-stage, low risk breast cancer. Clinic Provides Model for Risk Assessment and Personalized Advice for Breast Cancer Risk Reduction Specialists in the Cancer Genetics and Prevention Clinic provide expert, individualized genetic risk assessment and personalized plans for managing patients at high risk for developing breast cancer. Dedicated, Specialized Treatment for Triple-negative Breast Cancer The Breast Oncology Center provides expert consultation and care for difficult to manage breast cancer and research programs to better characterize the disease, identify biomarkers, and develop targeted drugs. Young Women s Program Provides Advanced, Specialized Breast Cancer Care Recognizing that young women with breast cancer face different concerns than older women, the Women s Cancers Program focuses care and research on unique issues for this population. Novel Biomarkers and New Treatments for Patients with Early-stage and Recurrent HER2-positive Breast Cancer Researchers in the Breast Oncology Center are seeking more effective and less toxic treatment approaches for women with HER2-positive breast cancer.

2 2 Breast Oncology Advances Advancement of Individualized, Personalized Surgery and Local Therapy for Breast Cancer to Minimize Treatment Surgical oncologists at Dana-Farber/ Brigham and Women s Cancer Center offer minimally invasive surgical approaches, including nipple-sparing mastectomy, perforator flap reconstructive surgery, image-guided surgery, as well as novel pre-operative medical treatment. Eric P. Winer, MD, Director, Breast Oncology Center, Dana-Farber/Brigham and Women s Cancer Center Jay R. Harris, MD, Chief, Radiation Oncology, Dana-Farber/Brigham and Women s Cancer Center Breast Cancer Highlights Comprised of subspecialty experts in surgical oncology, medical oncology, radiation oncology, pathology, and radiology, our multidisciplinary team: Provides innovative care to thousands of patients each year. In 2010, we cared for more than 7,200 patients with breast cancer; Offers an average of 60 clinical trials at a time, including trials that are expanding targeted therapies and changing the standard-of-care for many patients with breast cancer; Offers cutting-edge radiation therapies and planning techniques that maximize outcomes and minimize side effects; Pioneers basic science and translational research, supported by more than $15 million in funds each year, that is advancing the understanding of the risks, development, and prognosis in breast cancer. This issue of Breast Cancer Advances highlights a sampling of our latest activities including less invasive surgical procedures, innovative radiation techniques, genetics and breast cancer risk, research in triplenegative breast cancer, specialized breast cancer care for young women, and the latest treatments for HER2- positive breast cancer DFCI-BWH These advanced surgical techniques make it possible for a woman to have less invasive surgery, such as lumpectomy and skin-sparing or nipple-sparing mastectomies. Pre-surgical Individualized Therapy Mehra Golshan, MD, FACS, Clinical Director, Breast Center, Brigham and Women s Hospital, is collaborating with colleagues in medical oncology to study preoperative treatment, including targeted therapy such as Herceptin, chemotherapy, or a combination of drugs as a means of shrinking tumors and decreasing the need for more aggressive surgery. The benefits are two-fold: Minimal Surgery. If the patient responds to the medication, the tumor will shrink, thereby reducing the surgical intervention. Some patients may be able to undergo minimal surgical procedures; Improved Post-Operative Therapy. Identifying the drugs that are effective in shrinking an individual patient s tumor may help guide the use of postoperative therapy. Current trials of pre-operative therapy include: Paclitaxel With or Without Carboplatin and/or Bevacizumab Followed By Doxorubicin and Cyclophosphamide in Treating Patients With Breast Cancer That Can Be Removed by Surgery. In this Phase II trial, patients with triple-negative breast cancer are treated with standard chemotherapy or new chemotherapy regimens. This trial, led by Cancer and Leukemia Group B, will run through For more information regarding this trial, please contact Mehra Golshan, MD, FACS, at mgolshan@partners.org. Individualized Surgery for Metastatic Breast Cancer In the past, it was thought that patients with stage IV breast cancer that had spread to the lymph nodes, lung, liver, bone or brain did not benefit from surgery to remove the primary tumor. Recently, however, trials have begun to investigate the potential benefits of surgery for these patients, including: Early Surgery or Standard Palliative Therapy in Treating Patients With Stage IV Breast Cancer. This multi-center

3 Dana-Farber/Brigham and Women s Cancer Center 3 MRI image of a tumor before neoadjuvant treatment with chemotherapy or targeted drugs (left) and after (right). The tumor has shrunk, allowing surgeons to consider minimally invasive interventions such as focused ultrasound guided ablation rather than lumpectomy. Phase III trial of surgery for women with stage IV breast cancer will compare the surgical outcomes of patients to determine if surgery is beneficial in women with late-stage breast cancer. The study also will look to determine if there is a way to identify a subset of patients who will benefit from surgery. Also, it will assess the role of circulating tumor cells and other biomarkers to gauge the behavior of the cancer. The trial has not yet opened for patient enrollment. For more information regarding this trial, please contact Principal Investigator Mehra Golshan, MD, FACS, at mgolshan@partners.org. Skin- and Nipple-sparing Mastectomy The number of women electing to have mastectomies has increased in the last five years due in part to prophylactic surgery after identification of increased genetic risk. For women electing to have a mastectomy, they may opt for skin-sparing or nipple-sparing approaches to breast reconstruction. The reconstructive plastic surgeons in the Breast Oncology Center are leading trials of different surgical approaches, including: Nipple-sparing mastectomy for women undergoing mastectomy with reconstruction for risk reduction or early stage breast cancer (Stage 0-II). Imaging and clinical exam will be used to evaluate extent of disease and proximity to nipple to ensure that potential for nipple involvement is acceptably low. This also will be assessed on surgical pathology. The study will compare patient satisfaction with this procedure as compared to patients undergoing skin-sparing mastectomy and will include cosmetic outcome evaluations by plastic surgeons. Visit us online at dfbwcc.org to access our physician directory and learn more about our specialists and researchers. There have been quite a few studies that assess the mechanics of the procedure and outcomes, and the data suggests that the approach is safe, said Dana-Farber/ Brigham and Women s Cancer Center surgical oncologist Laura Dominici, MD. If it also improves the patient s overall quality of life, it would make this procedure very worthwhile. For more information regarding this trial, please contact Principal Investigator Laura Dominici, MD, at (617) or ldominici@partners.org. Image-guided Surgery The new Brigham and Women s surgical arena, opening in Spring, 2011, called the Advanced Multimodality Image- Guided Operating Room (AMIGO) will allow Dana-Farber/ Brigham and Women s Cancer Center surgeons to image the breast during surgery with MRI and PET scans to more clearly identify the edges of a tumor. Both MRI and PET scans allow surgeons to look for tissues with certain biological markers. Together, these imaging tools will help surgeons better determine if they have completely removed the tumor and should significantly reduce the frequency of repeat surgeries. Mehra Golshan, MD, FACS Clinical Director, Breast Center Brigham and Women s Hospital; Surgical Oncologist, Dana-Farber/Brigham and Women s Cancer Center Laura Dominici, MD Surgical Oncologist, Breast Oncology Center

4 4 Breast Oncology Advances New Radiation Techniques Reduce Risk of Organ and Tissue Injury and Offer Shorter Treatment Courses Radiation oncologists in the Breast Oncology Center are employing innovative techniques that reduce the risk of injury to the heart, lungs, and normal surrounding tissues during treatment and offer shorter radiation courses for patients with early-stage, low-risk breast cancer. In addition to providing the most advanced treatment options, we are dedicated to promoting the best quality-of-life possible for our patients, said radiation oncologist Jennifer R. Bellon, MD. Techniques provided by radiation oncologists in the Breast Oncology Center include: Deep inspiration breath hold delivers radiation treatment only during the deepest part of inspiration when the heart moves away from the chest wall. Radiation oncologists in the Center are among few in the nation to offer this technique, which helps to reduce the risk of injury to the heart and nearby organs; Canadian fractionation delivers a higher dose of radiation during each treatment in order to reduce the overall treatment course. Many breast cancer patients are eligible for Canadian fractionation, which involves 16 treatments compared with the standard six weeks of daily radiation therapy. Evaluation of patients 10 years post-treatment has shown excellent cosmetic results and local control that is comparable to longer radiation courses; Accelerated partial-breast irradiation offers another alternative to the standard six weeks of radiation therapy for patients with early-stage, low-risk breast cancer. External beam radiation is guided by cone-beam CT imaging to localize the lumpectomy cavity and deliver treatment using multiple conformal fields. Jay R. Harris, MD, Chief, Radiation Oncology, Dana-Farber/Brigham and Women s Cancer Center, is the lead author of a consensus statement from the American Society for Radiation Oncology outlining guidelines for appropriate patient selection for accelerated partial-breast irradiation (J Am Coll Surg Aug;209(2): Epub 2009 Apr 24.); Comparison of patient s anatomy with free-breathing (FB) and deep-inspiration breath-hold (DIBH) technique. The heart can be spared by using DIBH. Prone immobilization technique uses patient positioning to move the breast away from the chest. The technique helps to minimize skin toxicity and dose to underlying normal tissue, while protecting the heart and lungs from exposure. Evaluating Surgical and Radiation Outcomes Radiation oncologist Julia Wong, MD, is leading a new study that is evaluating the surgical complications and cosmetic outcomes in women who undergo immediate reconstruction followed by radiation. The reconstruction is combined with an acellular dermal matrix placed in the operting room to preserve continued on back cover This image illustrates how extent of DIBH is monitored by comparing patient s surface at the time of treatment with the reference surface from the CT sim.

5 Dana-Farber/Brigham and Women s Cancer Center 5 Clinic Provides Model for Risk Assessment and Personalized Advice for Breast Cancer Risk Reduction The Cancer Genetics and Prevention Clinic at Dana-Farber/ Brigham and Women s Cancer Center provides a model for individualized risk assessment and personalized advice for breast cancer risk reduction. For patients considering genetic testing for breast cancer, and for those who have already been tested elsewhere, we have outstanding genetic counselors, state-of-the-art technology, and many novel procedures and treatments, said Judy Garber, MD, MPH, Director, Center for Cancer Genetics and Prevention, Dana-Farber/Brigham and Women s Cancer Center. In addition to risk assessment, the Clinic offers expert genetic risk management and risk assessment for patients with elevated risks due to factors other than genetic inheritance. State-of-the-Art Management of Breast Cancer Risk Women who carry the BRCA1/2 mutations often opt to undergo surgery to reduce their risk of breast cancer and ovarian cancer. Procedures include elective oophorectomy, performed by dedicated gynecologic oncologists, and risk-reducing double mastectomy, performed by surgical oncologists such as Laura Dominici, MD, who is developing novel procedures for nipple-sparing mastectomy surgery. A reconstructive surgeon usually performs the reconstructions as part of the same procedure. In addition to prophylactic surgery, the Clinic is investigating novel preventive therapeutics, including: Evaluation of a PARP Inhibitor for Breast Cancer Prevention in BRCA Mutation Carriers. The Clinic received a Prevention Promise grant from the Susan G. Komen Foundation in 2009 to evaluate the use of PARP inhibitors to prevent breast cancer in BRCA1/2 carriers. This multicenter study, which will open for enrollment in early 2011, will be conducted for healthy women who have BRCA mutations and are planning prophylactic mastectomy. Women will be asked to take a PARP inhibitor, a new medication showing promise for its efficacy in treatment of breast and ovarian cancers in women with BRCA1/2 mutations, for four weeks leading up to their planned surgery. The goal of the study is to determine if PARP inhibitors have a future as prevention drugs, said Dr. Garber. These are very powerful agents, so we need to learn more about them to see if they have promise for the next generation. For more information, contact Principal Investigator Judy Garber, MD, MPH, at (617) or jegarber@partners.org. Neoadjuvant Trial of Lapatinib for the Treatment of Women with DCIS Breast Cancer. The goal of this work is to develop novel ways to help prevent HER2 positive breast cancer. The trial tests this possibility with Lapatinib, an oral medication used in the treatments of HER2-positive breast cancer, given to women for the brief period between the diagnosis of HER2-positive ductal carcinoma in situ and definitive surgery. For more information, contact Principal Investigator Judy Garber, MD, MPH, at (617) , jegarber@partners.org. Identification and Management of Non-genetic Breast Cancer Risk Factors Some patients may suspect they have an elevated risk of breast cancer, but they are not BRCA1/2 carriers. These patients may have concerns about their family history of breast cancer, may have pre-malignant lesions in a biopsy, or may have had radiation therapy that may put them at higher risk. Trials to find biomarkers of non-genetic breast cancer risk include: Statins and Breast Cancer Biomarkers. This multi-center study, done in collaboration with the University of Vermont, aims to determine if taking Atorvastatin (Lipitor) has an effect on breast density, a known risk factor for developing breast cancer. This study is currently recruiting patients. Vitamin D and Breast Cancer Biomarkers. This Cancer and Leukemia Group B study will evaluate the role of vitamin D in breast cancer risk. This study will be launched in early For more information on these biomarker studies, contact Principal Investigator Judy Garber, MD, MPH, at (617) or jegarber@partners.org. Access with One Call For more information or to set up a consult with a member of our team, please call to speak with one of our experienced referral coordinators. Judy Garber, MD, MPH Director, Center for Cancer Genetics and Prevention

6 6 Breast Oncology Advances Dedicated, Specialized Treatment for Triple-negative Breast Cancer The Breast Oncology Center at Dana-Farber/Brigham and Women s Cancer Center has a team of five dedicated breast pathologists who provide expert consultation for breast cancer cases that are difficult to manage. It s important for any triple-negative diagnosis to be unequivocal because there is no current targeted therapy for that subgroup. We want to make sure that these patients aren t really ER or HER2 positive, said Brigham and Women s and Dana-Farber/Brigham and Women s Cancer Center pathologist Andrea Richardson, MD, PhD. To better characterize triple-negative breast cancer, research programs at the Breast Oncology Center include efforts to better characterize the disease, identify biomarkers, and develop targeted drugs. An MRI scan showing a large triple-negative tumor (first image) and resolution of the cancer after completing cisplatin trial. Characterizing Triple-negative Breast Cancer Directed by Dr. Richardson, the Breast Tissue Bank, part of the Dana-Farber/Harvard Cancer Center Specialized Program of Research Excellence (SPORE), was established in It contains approximately 2,400 frozen breast tumor specimens. This tissue bank has contributed to the ongoing genetic characterization of breast cancer subtypes, such as work identifying the chromosomal changes involved in triple-negative breast cancer, published in Cancer Research (Cancer Research. Jan 2004;64:64-71), and work showing that BRCA1-mutant tumors and triple-negative tumors show similar phenotypes and gene expression signatures possibly related to defects in DNA repair mechanisms, published in Breast Cancer Research and Treatment (Breast Cancer Res Treat May;91(2):179-86). Dr. Richardson is now collaborating with the Broad Institute of Massachusetts Institute of Technology and the Sanger Genome Center, located in the United Kingdom, to involve this tissue bank in whole tumor genome sequencing studies. We are involved in global efforts to conduct sequencing of the tissue we have banked to try to identify the mutations in the genes that may be driving these tumors, said Dr. Richardson. Triple-negative Breast Cancer Biomarker Discovery Judy Garber, MD, MPH, Director, Center for Cancer Genetics and Prevention at Dana-Farber/Brigham and Women s Cancer Center, recently completed a clinical trial testing the use of cisplatin for patients with triple-negative breast cancer. Dr. Garber collaborated with Dr. Richardson in the analysis of tumor tissue collected before and after cisplatin treatment. The results of that trial, reported in the Journal of Clinical Oncology (J Clin Oncol Mar 1;28(7): ), showed that 22 percent of patients had a complete pathologic response, suggesting that a certain subtype of triple-negative breast cancers may be very responsive to cisplatin. Dr. Richardson and colleagues are now examining breast tissue banked from participants in this trial to find biomarkers that may help identify patients who will respond to cisplatin. We think that certain levels of chromosomal changes will predict who will be most sensitive to cisplatin, said Dr. Richardson, who presented preliminary results at the 2009 San Antonio Breast Cancer Symposium (abstract 111). The Search for a Targeted Drug for Triple-negative Breast Cancer Because there is no current targeted drug therapy for triplenegative breast cancer, Drs. Richardson and Garber are pur-

7 7 Young Women s Program Provides Advanced, Specialized Breast Cancer Care The molecular detail of triple-negative breast cancer. suing translational research into promising targets, including: PARP-inhibiting drugs. A PARP-inhibitor is currently in trial for tumors with BRCA mutations. Since PARP inhibitors have shown a lot of promise in the BRCA-mutant tumors, we hope they will be effective in sporadic triple-negative tumors, too, said Dr. Richardson. A PARP-inhibitor trial for triple-negative breast cancer is under development. The PARP-inhibitor trial for BRCA tumors, titled Evaluation of a PARP Inhibitor for Breast Cancer Prevention in BRCA Mutation Carriers, is underway at Dana-Farber/Brigham and Women s Cancer Center. For more information, contact Principal Investigator Judy Garber, MD, PhD, (617) , jegarber@partners.org. Judy Garber, MD, MPH Director, Center for Cancer Genetics and Prevention Andrea Richardson, MD, PhD Pathologist, Breast Oncology Center Dirk Iglehart, MD Director, Women s Cancers Program Young women diagnosed with breast cancer not only face decisions about treatment and fear of cancer recurrence, but often contend with issues unique to their young age. In particular, young women are more likely to have genetic predisposition to breast cancer and be concerned about how treatment will affect their fertility. Recognizing that young women face different issues than older women upon receiving a breast cancer diagnosis, Ann Partridge, MD, MPH, Clinical Director, Breast Disease Center, Dana-Farber/Brigham and Women s Cancer Center, and Eric Winer, MD, Director, Breast Oncology Center, Dana-Farber/Brigham and Women s Cancer Center, began to focus research on this population. In one of their first studies, they examined fertility concerns in a national sample of young women with a history of breast cancer. They conducted an internet-based survey of 1,700 young breast cancer survivors. The work, reported in the Journal of Clinical Oncology (J Clin Oncol Oct 15;22(20): ), identified a need for better communication with young patients about fertility issues, as well as a need for research into treatments that preserve fertility among young breast cancer survivors. This, and other studies identifying areas for improvement in care, led Drs. Partridge and Winer to establish the Program for Young Women with Breast Cancer in This Program, directed by Dr. Partridge, aims to: Support young women through their treatment; Educate both young women and their providers about the unique concerns of young women with breast cancer; Provide a model of comprehensive care intended to be adapted outside of the Dana-Farber/Brigham and Women s Cancer Center; Conduct research aimed to improve our understanding of breast cancer in young women including biology of the disease, response to therapy, and psychosocial and survivorship concerns. The Program brings together clinical researchers as well as basic and translational scientists from many fields including, pathology, medical oncology, radiation oncology and surgery as well as genetics, reproductive endocrinology, medical decision making, and more, making care highly multi-disciplinary, and research extraordinarily collaborative and translational, said Dr. Partridge.

8 Dana-Farber/Brigham and Women s Cancer Center 8 The Young and Strong website will be a password protected site for research participants. geared towards patients, such as booklets, videos, Questions for the Doctor, and resource links, and materials for oncologists such as checklists, book chapters, and clinical expert access. For the clinical care of patients in the Program, we help organize resources, such as fertility services, genetic screening, and psychological counseling, for young women to address their unique concerns. We want to be certain there are no missing pieces in care, said Dr. Winer. Patients also receive support from a social worker and access to telephone and drop-in support groups. The Program also reaches out to patients with a regular newsletter and hosts community-building events such as Survivor Evenings and an annual regional conference for patients. Young women definitely feel more comfortable here and appreciate the extra services, said Dr. Partridge. Expanding Care for Young Women The success of the Program has inspired expansion of clinical care and research beyond the local model program. The Virtual Young Women s Initiative Dr. Partridge received a three-year $1.35 million American Society of Clinical Oncology (ASCO) Cancer Foundation Improving Cancer Care Grant, funded by Susan G. Komen for the Cure. The grant supports her efforts to expand the domain of the Young Women with Breast Cancer Program into a virtual program, called the Young and Strong Program, that will reach women around the country. The virtual program will pilot and study exportable and sustainable educational and support materials for young women with breast cancer and their caregivers. Materials and interventions will include a community website that is geared to help patients and their doctors understand and address the concerns of young women. It will offer materials Visit us online at dfbwcc.org to access our physician directory and learn more about our specialists and researchers. Dr. Partridge is working with Co-principal Investigator Karen Emmons, PhD, Associate Dean, Research, in the Department of Society, Human Development, and Health, at the Harvard School of Public Health and a behavioral scientist with expertise in community-based research, to design the program and conduct the research. The team plans to export the model of care in the local Program for Young Women with Breast Cancer to community cancer settings and then study the effect of the expanded program on fertility issues and other measures of quality of care, satisfaction, and quality of life. They will evaluate the impact of their program versus an exercise-based intervention in a randomized clinical trial. Helping Ourselves, Helping Others In 2006, Dr. Partridge launched the first multi-institutional cohort study of young women diagnosed with breast cancer. The Helping Ourselves, Helping Others study has already enrolled more than 500 young women. The researchers will follow these women for 10 years, banking blood and tissue for biological analyses to better understand the unique biology of breast cancer in young women, as well as tracking the medical and psychosocial issues these women face at diagnosis and throughout treatment. For more information on all of these programs and studies, please contact Principal Investigator Ann Partridge, MD, MPH, at (617) , ahpartridge@partners.org. Ann Partridge, MD, MPH Clinical Director, Breast Oncology Center; Director, Program for Young Women with Breast Cancer Eric P. Winer, MD Director, Breast Oncology Center Dana-Farber/Brigham and Women s Cancer Center

9 9 Breast Oncology Advances Novel Biomarkers and New Treatments for Patients with Early-stage and Recurrent HER2-positive Breast Cancer HER2-positive breast cancer research at the Breast Oncology Center is focused on finding less toxic drug combinations for patients with early-stage breast cancer, novel biomarkers to help identify subtypes of HER2-positive cancer that guide treatment, and effective drug combinations for the treatment of more advanced metastatic breast cancer. Less Toxic Drug Regimens for Patients with Advanced Breast Cancer For women with HER2-positive breast cancer, standard treatment involves a combination of chemotherapy and trastuzumab (Herceptin), the same treatment women in later stages of the disease receive. We do not have a lot of data for what to give patients with smaller, earlier stage tumors, said Dana-Farber/Brigham and Women s Cancer Center medical oncologist Nancy Lin, MD. Clinical trials typically look at Stage II or higher breast cancer, so they have tested very intensive chemotherapy agents. This leads to a gap for oncologists in practice. As a result, researchers in the Breast Oncology Center tested a less toxic drug regimen for women with small tumors and negative lymph nodes. Adjuvant Paclitaxel and Trastuzumab for Node-negative HER2-positive Breast Cancer. This Phase II clinical trial tested a combination of trastuzumab and paclitaxel, given for 12 weeks, followed by trastuzumab alone for nine months. This drug combination is shorter and is thought to be better tolerated than the standard regimens used in patients with lymph node-positive breast cancer. This Phase II trial sought to test the effectiveness of this drug combination is when used in women with early stage breast cancer and to better define the side effects. Researchers are currently evaluating the results of this trial, which recruited 400 patients and recently concluded. For more information, please contact Principal Investigator Eric Winer, MD, (617) , ewiner@partners.org. For women with more advanced cancer, less toxic and more effective treatments are also under evaluation. Novel Antibody-guided Treatment with T-DM1 for Earlystage Breast Cancer. A recently completed Phase II study, led by Dana-Farber/Brigham and Women s Cancer Center medical oncologist Ian Krop, MD, PhD, involved 110 patients with HER2-positive metastatic breast cancer. Patients received T-DM1, an antibody-drug conjugate that selectively delivers the potent and toxic drug DM1 directly into HER2-positive tumor cells. The drug does not cause the side-effects such as hair loss, cardiac damage, and gastrointestinal side effects, that DM1 causes when it is delivered systemically. The study found that about 40 to 45 percent had clinical benefit from the treatment. Dr. Krop, who also led a Phase I study of T-DM1 and published the results in the Journal of Clinical Oncology (JCO June 1, 2010 vol. 28 no ), presented these preliminary Phase II results at the San Antonio Breast Cancer Symposium in 2009 (Abstract 5090). Using Circulating Tumor Cells to Guide Treatment of Metastatic Breast Cancer While counting tumor cells that circulate in the blood has prognostic value, Dr. Krop has expanded on this capability by molecularly characterizing CTCs collected from breast cancer patients. Krop found that about 30 percent of women with HER2-negative breast cancer based on their primary tumor biopsy have clinically significant levels of HER2-positive CTCs. This work appeared in the British Journal of Cancer (Br J Cancer 2010 May 11;102(10): ). It isn t clear yet if this finding indicates that these women have heterogeneous tumors or if their tumors have simply evolved to take on a HER2-positive status, said Dr. Lin. It is potentially clinically significant, however, because we have drugs like trastazumab which may provide benefits to this subset of patients. Dr. Krop is launching a study to determine if trastuzumab is effective in treating these women with discordant tumor and CTC HER2 status. A Phase II, Open Label Study to Evaluate the Efficacy and Safety of Trastuzumab and Vinorelbine in Advanced Breast Cancer Patients with HER2 Non-Amplified Primary Tumors and HER2 Amplified Circulating Tumor Cells. This study will recruit 35 women who have HER2-negative breast cancer. These women will have their CTCs analyzed continued on back cover Ian Krop, MD, PhD Medical Oncologist, Breast Oncology Center Nancy Lin, MD Medical Oncologist, Breast Oncology Center Harold J. Burstein, MD, PhD Medical Oncologist, Breast Oncology Center

10 New Radiation Techniques Reduce Risk of Organ and Tissue Injury and Offer Shorter Treatment Courses continued from page 4 the normal breast contour, enhancing the cosmetic result. This study is currently enrolling patients. Please contact Principal Investigator Julia Wong, MD, at (617) for more information. Weighing Treatment Options for DCIS Radiation oncologist Rinaa Punglia, MD, MPH, is the scientific Principal Investigator of a grant from the Agency for Healthcare Research and Quality (AHRQ) within the U.S. Department of Health and Human Services to study the comparative effectiveness of treatment strategies for ductal carcinoma in situ (DCIS). The study aims to provide a decision aid that physicians may use with their patients to better inform and individualize decision-making for DCIS. Investigators will analyze two multi-institutional datasets to delineate long-term outcomes of treatment choices for DCIS, including lumpectomy with or without radiation therapy and mastectomy. The results will be incorporated into a model which will provide individualized estimates for each treatment strategy. A web-based decision aid will be created using the results of the model to display the benefits and drawbacks associated with each strategy. Comparison of patient s anatomy in supine and prone setup. The heart can be avoided by using prone technique. Jay R. Harris, MD Chief, Radiation Oncology Dana-Farber/Brigham and Women s Cancer Center Jennifer R. Bellon, MD Radiation Oncologist, Breast Oncology Center Rinaa Punglia, MD, MPH Radiation Oncologist, Breast Oncology Center Julia Wong, MD Radiation Oncologist, Breast Oncology Center Novel Biomarkers and New Treatments for Patients with Early-stage and Recurrent HER2-positive Breast Cancer continued from page 9 and, if they have a clinically significant level of HER2-positive CTCs, they will be given a Herceptin and chemotherapy regimen. For more information on this study, please contact Principal Investigator Ian Krop, MD, PhD, (617) , ikrop@partners.org. Dr. Lin and medical oncologist Harold J. Burstein, MD, PhD, have conducted other trials in patients with HER2-positive advanced breast cancer. Dr. Lin s work has focused on the treatment of HER2-positive breast cancer when it has spread to the central nervous system. Unfortunately, this is a common problem and there is an urgent need for more effective treatments. Dr. Burstein has conducted a wide range of clinical trials in women with HER2-positive breast cancer. He has studied combinations of drugs in the preoperative setting and has evaluated several new compounds in women with advanced HER2-positive disease. In particular, he was the lead investigator on a trial that studied the drug neratinib in women with refractory breast cancer. This agent may well gain approval for women with HER2-positive breast cancer in the next one to three years. Dana-Farber Cancer Institute Brigham and Women s Hospital 450 Brookline Avenue 75 Francis Street Boston, MA Boston, MA DFCI-BWH