The primary objective of the Fourth Annual Symposium on Personalized Therapies and Best Clinical Practices for Breast Cancer and its corresponding enduring materials is to help you develop subsequent improvements in your practice so that you can treat your patients with the optimal personalized approaches in order to improve patient outcomes and minimize drug-induced toxicities. These CME activities are especially designed to help you incorporate the extensive practice-changing clinical and scientific data on breast cancer presented at the 2010 annual ASCO meeting, and at other important meetings in 2010 including AACR in March, and also what we discovered from publications and interviews and focus groups with the attendees at the Third Annual Symposium on Personalized Therapies and Best Clinical Practices for Breast Cancer held this past February 6, 2010. The two new CME activities will also include updated information from the October 2010 Breast Cancer Symposium and the December 2010 San Antonio Breast Cancer Symposium as needed.

This symposium is "case-based" learning. The symposium format extensively utilizes adult learning principles. The learning design is one that is very highly interactive between the learners and the faculty. Each didactic presentation begins with a patient case study and the faculty uses the Audience Response System (ARS) for engaging you, the learner, at the outset of each segment of the program. This approach has been so successful that it is used for all of our live symposia to further facilitate adult learning. In addition, each of the symposium’s sessions will include one additional, dedicated, interactive clinical case studies session involving you and the faculty with ARS. The symposium will include a Point-CounterPoint debate in Session 1. You will vote on the Point-CounterPoint debate via ARS for additional interaction with the faculty. Each symposium session will include a 15-minute Roundtable Faculty Panel Discussion so that you can be prepared to apply the data presented and reviewed to improve your practice. And each symposium session will conclude with a 15-minute Q & A period for additional involvement with the faculty.

Many of the expert faculty of the 3rd Annual Symposium on Personalized Therapies and Best Clinical Practices, the expert faculty of this forthcoming 4th annual symposium to be held on January 22, 2011 in La Jolla, CA, and several additional key opinion leader breast cancer experts provided us with the IDEAL or “best practices” for treating breast cancer with personalized therapies. The previous symposium’s audience of learners, and numerous additional community-based, non-academic oncologists and hematologist/oncologists and allied healthcare professionals who treat patients with breast cancer helped to provide us with the BASELINE or “current practices.” From the differences between the IDEAL and BASELINE practices we developed the Practice Gaps for this Needs Assessment.
For these two CME activities (January 2011 live symposium and corresponding Internet-based enduring materials) numerous focus groups and personal interviews were conducted during the past several months, beginning in February 2010, in June 2010 during the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, IL, and subsequently with more than thirty academic experts and also with more than forty community-based, non-academic oncologists and hematologist/oncologists and allied healthcare professionals involved in the treatment, care and management of patients with breast cancer.

The community-based practitioners helped us identify a overal Practice Gap: There is simply too much new information now available for molecular testing of breast cancer patients, and for the new drugs and indications of existing drugs. Moreover, the rate at which this new information is becoming available is constantly increasing. Much of the important new scientific and clinical data for breast cancer includes clinical trials’ results that are helping facilitate the identification of and the improved treatment of three major breast cancer patient sub groups and personalized therapies for them. The academic experts pointed out that there were several abstracts and sessions at the 2010 ASCO meeting including new data on existing and emerging biomarker tests that can further help identify these breast cancer subtypes and the optimal use of corresponding personalized therapies.

The large amount of new testing information for HER2 breast cancer patients is critical for patients who either fail to respond or who have relapsed on current therapies, especially with the emergence of new and multiple therapies for treating this breast cancer subtype. The academic experts also mentioned that there were several abstracts and sessions at the 2010 ASCO meeting on the subjects of the existing and also of the new gene-based assays that help with the identification of hormone-receptor positive patients who might better respond to endocrine therapy and to chemotherapy. One 2010 ASCO abstract was actually designed to review the role of personalized therapy with a drug that is approximately 40 years old, tamoxifen.

New data regarding BRCA1 and BRCA2 testing was also revealed at the 2010 ASCO meeting. The academic experts indicated that this is important for developing optimal and personalized systemic regimens involving PARP inhibitors and also for identifying breast cancer patient subgroups who may better benefit from platinum-based therapies. And there were several abstracts and posters on the biomarker, SPARC (Secreted Protein acidic Rich in Cysteine) that were presented along with several clinical studies for which SPARC was used for nab paclitaxel for breast cancer therapy in various treatment settings. Subsequently, there have been data with circulating tumor cells, and the availability of a cytoplasmic PARP assay, and further usage of both the commercially available 70-gene DNA micro array-based in vitro test, and the 21-gene assay all help determine therapy selection and disease recurrence in some patients.

In addition, just prior to the June 2010 annual ASCO meeting, the College of American Pathologists and the American Society of Clinical Oncology issued “game-changing’ new joint guidelines (April 19, 2010) for immunohistochemistry (IHC) testing for the expression status of estrogen and progesterone receptors in breast cancer. The main goal of the new ASCO/CAP ER/PgR guidelines is to improve the accuracy of IHC test results and ensure that patients receive appropriate care with endocrine therapy, as it has the potential to improve survival and save more lives. Widespread access to accurate ER/PgR testing is critical. IHC is commonly used to measure the amount of ER and PgR proteins in breast cancer cells, which can help guide treatment with endocrine therapies, such as tamoxifen, that have shown to improve survival. However, between 10 and 20 percent of IHC test results may be inaccurate, yielding false-positive or false-negative results, according to an ASCO/CAP joint statement announcing the new published guidelines. Hormone-receptor positive is the most common breast cancer phenotype worldwide. Therefore, access to accurate and reliable ER/PgR testing and established and relatively affordable endocrine therapies could have a profound impact on breast cancer outcomes in high- and low-/middle-income countries around the globe. This new ASCO/CAP guideline information has an impact on the treatment of ER-positive disease but also, as the experts pointed out to us, it importantly, impacts the number of patients who are classified as, and consequently treated as having triple-negative breast cancer.

This increasing number of diagnostic tests and molecular classification data and biomarkers, prompted the experts to raise the following additional “questions in practice” that remain components of the overall key Practice Gap for biomarkers and testing of breast cancer patients: For which patients with breast cancer are these various tests such as tests for HER2 status, IHC, FISH, CYP2D6, and others most appropriate and useful? What are the appropriate clinical applications of gene-based testing? What are the clinical applications of the quantitative mRNA genetic test? What are the molecular predictors of response to adjuvant endocrine therapy? Is there a patient subtype, for whom we should test for cytoplasmic PARP? And perhaps, most importantly, how does each test help oncologists with improved decision making as they decide how to treat their patients with breast cancer?

The experts told us that there still exists a difference between the IDEAL and BASELINE practices for personalizing radiation and surgical therapies for local-regional control of breast cancer. The KOLs also reminded us that the primary goal of neoadjuvant breast cancer therapy is the conversion of inoperable disease to operable disease. There is also potential to downstage involved axillary nodes and reduce axillary surgery. Reducing the need for radiation therapy is another potential outcome of effective neoadjuvant therapy. Long-term benefits with increase local-regional control of the disease through neo-adjuvant therapy and radiation may result in better long-term outcome. The personalized use of neoadjuvant therapy is evolving and therefore there is a need to educate physicians on this topic to improve patient outcomes.

We were also informed by the experts that because of the large amount of new clinical data presented at the 2010 ASCO meeting and from other sources on the three major sub types of breast cancer, HER2 disease, ER-positive disease, and Triple Negative Disease (TND), the following approaches should be used for Practice Gap development and subsequent learning objectives and content development to help clinicians close their Practice Gaps with our two CME activities. Establish four distinct learning sessions: one session for reviewing the IDEAL therapies for each of the three breast cancer subtypes (ER-Positive Disease, HER2 Disease and Triple-Negative Disease) and then, also establish one separate session for presenting the IDEAL methods for treating patients with systemic and local-regional therapies used for all subtypes of breast cancers to ensure that all Practice Gaps are addressed. In this fourth session they told us to also include bone health and skeletal-related events. Key questions in practice that we identified in our various interviews, surveys and focus groups helping us with the development of Practice Gaps include the following:

• ER-Positive Disease: What is the role of combining targeted therapies with hormonal therapies? When do you switch from hormonal to chemotherapy? When do we add adjuvant chemotherapy to hormonal therapy and radiation therapy? What are the current thoughts on individualizing aromatase inhibitor therapy duration according to the risk of disease recurrence? Is there sufficient evidence to use the CYP2D6 test that measures the fast versus slow polymorphisms where the pro drug, 4-hyrdoxy tamoxifen, is metabolized to endoxifen in order to determine the optimal use of tamoxifen?

• HER2 Disease: Although this question has been “alive for a few years”, which chemotherapy should be used – anthracycline or non-anthracycline-based regimens? Which dosing schedule should be used – concurrent or sequential chemotherapy and trastuzumab? What is the duration of therapy, e.g., 3 or 6 months? 1 year? 2 years? Other? How do you manage patients with abnormal ejection fraction during therapy? Does HER2 status matter with adjuvant trastuzumab? What are the clinical roles of T-DM1, pertuzumab and neratinib? For initial therapy of metastatic disease, what regimen should be given in the front-line setting and what are the criteria for determining therapy – prior therapy, time to disease progression after adjuvant therapy, etc.? For HER2 failures or relapsed patients with metastatic disease, what regimen should be given and why, including the enrollment of patients in clinical trials? What newly FDA-approved therapies can we expect in late 2010 and early 2011? Should patients be treated beyond disease progression? What are the optimal anti-HER2 drug combinations – do any show a survival benefit?

• Triple-Negative Disease: What impact do the CAP/ASCO guidelines have on this patient subpopulation? Triple-negative breast cancer patients are a heterogeneous group of patients, not just one phenotype – how does this affect testing and drug selection, including existing and experimental therapies? What newly FDA-approved therapies can we expect in late 2010 and early 2011? For the adjuvant setting, which chemotherapy should be used? – anthracycline or non-anthracycline-based regimens AC? TC? TAC (TC plus bevacizumab)? For neoadjuvant triple-negative breast cancer, for which patients should platinum-based regimens be used?

This review with the experts permitted an integrated design for analyzing a large amount of data on existing drugs as well as investigational new agents including anti-HER2 therapies, dual anti-HER2 and anti-angiogenic inhibition, new targets such as PARP inhibition, multi-kinase inhibitors, other novel targeted therapies such as inhibitors of mTOR and novel chemotherapeutics such as microtubule-targeting agents and novel forms of taxanes, newer monoclonal antibodies and other intracellular pathways and targets for breast cancer, which in most cases are ideal for the development of personalized therapies.

The experts told us about the very important new data regarding the new agent, denosumab, which has been FDA-approved this past year for post-menopausal women at high risk for osteoporotic fractures. This agent has also demonstrated favorable efficacy in preventing skeletal-related events (SREs) in breast cancer patients with bone metastasis. And although denosumab has not yet received an indication for breast cancer it is being prescribed by many experts and thus, is an important new Practice Gap. In addition, the experts reminded us of the clinical evidence from 2 years ago which demonstrated that zoledronic acid is another option for SREs and that it also may provide an anticancer benefit in early-stage breast disease, supporting the potential use of early/concomitant intervention with zoledronic acid in the adjuvant setting. Overall, these data warrant further consideration of both zolendronic acid as well as denosumab in certain breast cancer patients. And there may likely soon be a role for a novel, first in class, radium 223 agent in breast cancer, as this agent is currently under evaluation for treating bone metastases in prostate cancer and expanding its clinical evaluation into the treatment of patients with breast cancer. The need to better understand how to use these bone-targeted agents for treating and managing SREs in breast cancer patients is also a Practice Gap.

The experts also told us that for the first time in years, new data has recently emerged for the topic of improved treatment for brain metastases. This new data will be reviewed in the literature and other data sources of this document and will be a topic addressing some questions in practice at our January 22, 2011 CME symposium.

Finally, we are aware that there are at least two major breast cancer meetings that will occur between the current development of this Needs Assessment and Practice Gap identification and the symposium on January 22, 2011, so we have structured the learning objectives of our two CME activities to be able to accommodate any new data and resulting Practice Gaps arising from the Breast Cancer Symposium in October 2010 in Washington, DC, and the December 2010 San Antonio Breast Cancer Symposium.

The more than forty community-based, non-academic medical oncologists, hematologist/oncologists and other allied health care professionals who treat, care for and manage patients with breast cancer that we interviewed or engaged in dialogues in focus groups unanimously corroborated the above-mentioned information that was identified by the experts in our direct measurements with them. Specifically, the community-based, non-academic target audience stated that they were still unclear in many areas regarding how to optimally personalize their therapies for both early and advanced/metastatic breast cancer patients, especially with the release this past year of a steadily increasing amount of new molecular biomarker testing data and also new data on the effectiveness of several existing and investigational agents. As stated above, and repeatedly to us throughout the past year’s discussions with them, there is simply too much new information for them to digest and apply in the clinic, and especially because they deal with information with multiple tumor types. They all agreed that Practice Gaps are expanding and look forward to both the live course on January 22, 2011 and the corresponding Internet-based enduring materials to help them close their Practice Gaps.

The community-based oncologists, hematologists/oncologists and allied healthcare professionals in a true sense, are generalists, who do not have the time and luxury of learning only one tumor type. They also repeatedly tell us that the regional one-day symposia and on demand Web-based CME such as what is planned as the basis of this grant is a most convenient way for them to digest and continually work to close the many Practice Gaps resulting from this new information, especially regarding newer and personalized drug therapies for breast cancer. The alternatives to our CME, they tell us, such as CME from ASCO, NCCN and other major society conferences are too big, lack the focus, practicality and case-based interaction that helps them learn.