Report from the 34th Annual San Antonio Breast Cancer Symposium, December 6-10, 2011

The 34th San Antonio Breast Cancer Symposium (SABCS), the world's largest annual breast cancer meeting, attracted nearly 8,000 participants from more than 90 countries. This year's assembly centered on emerging treatments for challenging breast cancer subtypes and metastatic disease, as well as on new knowledge about prevention and risk. Findings from several important studies with potential impact for women with HER2+ breast cancer and metastatic disease were announced.

Following the tribute to Evelyn H. Lauder and her legacy in breast cancer research, SABCS proceedings began. Among the many highlights, several advances in clinical care for metastatic breast cancer were reported at this year's meeting. The limiting step of any cancer therapy is resistance. When a new therapy is applied, patients either do not respond from the very beginning or initially benefit from the therapy but eventually develop resistance. Based on earlier studies funded in part by BCRF, researchers have designed and developed clinical trials to see if various combinations of existing therapies would overcome resistance and improve results for patients. Results from two large-scale, international clinical trials on combinatorial therapy were reported.

Clinical Innovations

As harbinger for future success, several advances in clinical care for metastatic breast cancer were reported at this year's meeting. The limiting step of any cancer therapy is resistance. When a new therapy is applied, patients either do not respond from the very beginning or initially benefit from the therapy but eventually develop resistance. Based on earlier studies funded in part by BCRF, researchers have designed and developed clinical trials to see if various combinations of existing therapies would overcome resistance and improve results for patients. Results from two large-scale, international clinical trials were announced at SABCS and published in the New England Journal of Medicine.

BOLERO-II is a phase III randomized clinical trial of postmenopausal women diagnosed with metastatic hormone receptor positive (HR+) breast cancer from 195 sites worldwide. This trial examined the efficacy of combining exemestane (an aromatase inhibitor used to treat HR+ breast cancer) with everolimus (Affinitor®), which is a new kind of medicine that inhibits an intracellular signal called "mTOR" thought to be important in most HR+ breast cancers. Gabriel Hortobagyi, MD (University of Texas, MD Anderson Cancer Center), a member of BCRF Executive Board of Scientific Advisors, presented findings that suggest the addition of everolimus to exemestane more than doubled the length of time (from 3.2 months to 7.4 months) the patients' tumors responded to treatments. Because this drug is already FDA-approved for other diseases the combination provides an additional clinical option for these women.

Results from CLEOPATRA, another international phase III trial, were also reported. This trial looked at the benefit of combining trastuzumab and pertuzumab, both anti-HER2 antibodies. In a population of 808 patients with metastatic HER2+ breast cancer, José Baselga, MD, PhD (Massachusetts General Hospital), reported that women who received the combinatorial therapy experienced on average 18.5 months of progression-free survival, as compared with 12.4 months to those who received only one anti-HER2 drug. He also reported an improvement in the duration of overall survival. These findings, if they persist, are likely to change clinical practice for patients with advanced HER2+ breast cancer if and when this drug receives FDA approval.

Also, James Ingle, MD (Mayo Clinic, Rochester), provided a thoughtful analysis of studies on combinatorial therapies for metastatic HR+ breast cancer. Confirming earlier studies by Angela Hartley-Brodie, PhD, 2010 Jill Rose Award recipient, adding fulvestrant to anastrozole as first-line therapy prolonged both progression-free survival and overall survival for postmenopausal women, especially for those who had not been previously treated with aromatase inhibitors. In addition, the role of bisphosphonates, drugs designed to strengthen bones, in breast cancer recurrence prevention was explored in several studies. Results suggest that zoledronic acid and clodronates may reduce the incidence of metastasis in both pre- and post-menopausal women with HR+ breast cancer. These data provide encouragement for continued investigations.

Chairman of BCRF's Scientific Advisory Committee, Clifford Hudis, MD (MSKCC), led the discussion on posters on new chemotherapy clinical trials. Dividing the projects into two groups, adjuvant vs. neoadjuvant, Dr. Hudis insightfully assessed these studies examining the effectiveness of various combinations of existing drugs. Michael Press, MD, PhD (University of Southern California) reviewed the set of posters on current and developing treatments for HER2+ breast cancer. Drs. Hudis and Press raised important questions on toxicity and other considerations impacting both clinician choices and patient outcome.

In radiation oncology, Benjamin D. Smith, MD (University of Texas, MD Anderson Cancer Center) and colleagues assessed the health outcomes of 130,535 women aged 66 years and older with invasive breast cancer treated with brachytherapy, a form of radiotherapy where a radiation source is placed inside or next to the area requiring treatment. Dr. Smith and colleagues found that compared with women treated with whole-breast irradiation, women treated with brachytherapy experienced a twofold increased risk (4% vs. 2.2%) for subsequent mastectomy. These women were also more likely to experience radiation-related side effects, such as breast pain, fat necrosis, and rib fracture. Dr. Smith cautioned that additional data from randomized clinical trials are needed before widespread adoption of breast brachytherapy.

In survivorship studies, Patricia Ganz, MD (University of California, Los Angeles), member of BCRF's Scientific Advisory Board whose pioneering work has elucidated the unique needs of breast cancer survivors, discussed new data on presented at the meeting. Of interest were the reports from the clinical trial groups of National Cancer Institute of Canada on the use of exemestane for breast cancer prevention and impact on the quality of life. While exemestane did cause some negative side effects, it is mostly well-tolerated by study participants with under 6% drop-out rate after one year. Also, Dawn Hershman, MD, MS (Columbia University Medical Center), led the discussion of posters on survivorship, covering body image, cognitive and fatigue issues, and sexual functioning. At a later session, Dr. Hershman also presented findings from an original, retrospective study where she and colleagues found that only about one-third of women undergo immediate breast reconstruction after mastectomies. The availability of insurance coverage seemed to influence women's decisions. Also, Richard C. Zellars, MD (Johns Hopkins University) shared findings from his retrospective study of the rate of reconstruction surgery following radiation therapy.

SABCS also serves as an educational forum for researchers and practitioners. On the afternoon preceding the official opening of the sessions, several BCRF grantees served as panelists in educational sessions focused on treatment of metastatic breast cancer as chronic disease, laboratory models of PI3K-dependent and basal-like breast cancer, controversies in early breast cancer, and new technologies in biomarker discovery. Member of BCRF's Scientific Advisory Committee, Vered Stearns, MD (Johns Hopkins University) spoke about the management of triple negative breast cancer and discussed existing and developing therapeutic options. Angelo Di Leo, MD, PhD (Hospital of Prato, Instituto Toscani Tumori) presented four case studies of adjuvant therapy in patients with borderline HER2+ status and provided helpful suggestions for other clinicians should they encounter similar situations.

In addition, throughout the Symposium, several BCRF grantees conducted a mini-symposium on studies in the neoadjuvant, or pre-operative, setting, where the application of chemotherapy (either systemic or targeted) takes place prior to tumor removal. In the mini-symposium on neoadjuvant studies, Lisa A. Carey, MD (University of North Carolina, UNC), provided an overview of several ongoing projects that will elucidate the effectiveness of novel therapies, such as TDM1 and PARP inhibitors, in the treatment of HER2+ and triple negative disease. Ian Smith, MD (Royal Marsden Hospital), covered neoadjuvant endocrine therapy, while Carlos L. Arteaga, MD (Vanderbilt University School of Medicine), Co-Director of SABCS, focused on using neoadjuvant therapy to inform laboratory studies. These presentations pointed out the importance of these investigations in making progress in breast cancer care, as they tend to be smaller scale (and therefore faster to accrue) and could introduce laboratory advances more quickly to the clinical setting. Also, embedded in neoadjuvant research is the opportunity to develop biomarkers to predict patient response and/or disease progression, which will be the key to success in cancer care.

Laboratory Advances

There were also several presentations focused on basic science research. Gordon Mills, MD, PhD (University of Texas, MD Anderson Cancer Center), provided an energetic overview of the use of proteomics, the study of proteins, in breast cancer research. He illustrated how proteomics could produce insights into biomarker discovery and development and single-cell analysis, which are two of the main objectives of gene-based investigations in cancer. Geoffrey M. Wahl, PhD (Salk Institute for Biological Studies) also provided a look into the relationships among p53, which is a tumor suppressor protein, stem cells, and breast cancer. His work has elucidated the differences between cancer stem cells and certain adult cancer cells that have been converted into a stem cell-like state. In addition, Lajos Pusztai, MD, PhD (MDACC), member of BCRF's Scientific Advisory Committee, in a later presentation reported results from his investigations assessing the type and prevalence of mutations in cancer-related genes, which differed among the various breast cancer subtypes.

Rachel Schiff, PhD (Baylor College of Medicine) moderated the basic science session devoted to tumor heterogeneity and metastasis. Robert Benezra, PhD (MSKCC) focused his talk on tumor-entrained neutrophils, which are a form of white blood cells in our body's nature defense system. He spoke about his work studying metastasis of lung cancer cells and how it has been applied towards breast cancer studies. Matthew J. Ellis, MB, BChir, PhD (Washington University School of Medicine) focused his presentation on tumor heterogeneity and metastasis, analyses that resulted from his successful decoding the whole genomes of tumors from 50 breast cancer patients and comparing them to the matched DNA of the same patients' healthy cells to find mutations that only occurred in the cancer cells.

In a special session, Charles M. Perou, PhD (UNC) reported on the highly anticipated data from The Cancer Genome Atlas (TCGA) and International Genomics Consortium. On behalf of TCGA, Elaine R. Mardis, PhD (Washington University School of Medicine) shared results and interpretations on TCGA breast cancer sequencing efforts, which aim to identify the most frequent genomic changes in breast tumors, to determine which genomic changes are linked to better outcomes or may predict recurrence or metastasis or may predict response to different kinds of therapies. This special report was followed by a "year in review" led by BCRF grantees who covered the topics of advances in basic science research, translational research, and treatment for early and metastatic breast cancers.

The SABCS also provided a forum to recognize individuals in the breast cancer community who have made dramatic impact on breast cancer care and research. Joan S. Brugge, PhD (Harvard Medical School) delivered the AACR Distinguished Lectureship in Breast Cancer on protective adaptive responses to breast cancer therapies. Dr. Carlos Arteaga received the Susan G. Komen for the Cure Brinker Award for Scientific Distinction and delivered the lecture on oncogenes and estrogen receptor positive (ER+) breast cancer.

In sum, many of the investigations that were initiated with BCRF funding and reported at the San Antonio conference this year, announced results with clinical significance for women who have experienced, or are at risk of developing, breast cancer.