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© Copyright 2003 – 2008 Institute for Medical Education & Research, Inc. All Rights Reserved.

With advances in the understanding of cellular and molecular signaling transduction in breast cancer, novel biologic therapies that target a variety of signaling pathways have emerged within the last decade. More recently, therapies acting on targets involved in tumor angiogenesis and proliferation in breast cancer have demonstrated positive results, which will lead to changing paradigms in breast cancer treatment. Also, based on positive outcomes of recent clinical trials, targeted therapies are now being employed in the adjuvant setting.ighlighting current research in breast cancer, colorectal cancer, lung cancer, head and neck cancers, and oncology supportive cancer care topics.

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TARGETED THERAPIES IN BREAST CANCER: CHALLENGING QUESTIONS FROM ONCOLOGY NURSES

Program Overview

In recent years, paradigm shifts in the multimodal treatment of breast cancer have occurred based on the successful incorporation of targeted therapies. Since 2004, several educational initiatives on this topic have been held, and excellent oncology nurse questions worthy of detailed responses have been submitted, addressing such issues as targeted therapy mechanisms of action, current and expected future targeted therapy clinical applications, and nursing management strategies. During this interactive, 2-hour educational program, expert panelists will present these frequently asked questions. Attendees’ understanding of presented issues and their own practice patterns will be questioned via audience response technology. Finally, the program will conclude with a tribute to singer-songwriter Soraya, who lost her battle with breast cancer in 2006. Soraya was a national spokesperson for breast cancer causes and urged women everywhere to empower themselves and make educated treatment choices.

Learning Objectives

Upon completion of this program, participants should be better able to:

Explain the rationale for targeting cellular signaling pathways in the treatment of breast cancer
Describe current indications for and recent clinical trial data on targeted therapies in early invasive breast cancer
Describe current indications for and recent clinical trial data on targeted therapies in metastatic breast cancer
Identify administration guidelines for targeted therapies used in the treatment of breast cancer
Demonstrate proper management of common toxicities caused by targeted therapies used in the treatment of
breast cancer

Program Abstracts

BREAST CANCER TARGETED THERAPY MECHANISM OF ACTION

G. Lita Smith, RN ACNP

As we have learned more about the biology of breast cancer and the important components that drive breast cancer growth, it has become apparent that not all breast cancers are alike and that breast cancers require individualized treatment. It has also become clear that although chemotherapy may enhance outcomes for patients with early stage and recurrent metastatic disease, only a fraction of those who receive such treatment benefit from it. Chemotherapy alone in the metastatic setting has not been found to be curative. Chemotherapy also has substantial toxicities associated with its use. Over the years, researchers have discovered key receptors such as ER/PR and HER2 that are important in stimulating breast cancer cells and signaling cellular growth, proliferation, and survival (the signal transduction pathway). The signal transduction pathway is incredibly complex and we are only beginning to understand the whole system and identify important targets to manipulate as a means of killing cancer cells. Targeting the ER/PR and HER2 receptors, through the use of therapies such as tamoxifen and trastuzumab, has significantly improved the outcomes of many patients with both early and advanced stages of breast cancer. Vascular endothelial growth factor (VEGF), a key component in angiogenesis, is vital for cancer cell growth, metastasis, and survival. Bevacizumab is a monoclonal antibody that targets and inhibits VEGF, thereby suppressing angiogenesis. The epidermal growth factor receptor (EGFR) is another receptor important to cellular stimulation. Lapatinib, which targets and inhibits both EGFR (HER1) and HER2, has recently been shown to improve disease-free survival in combination with capecitabine in the treatment of metastatic breast cancer, and may provide benefit to patients who are refractory to trastuzumab therapy. What is quickly becoming a reality is the idea of identifying each individual’s “biologic blueprint” in terms of the factors that are driving and signaling the breast cancer to grow and the extent to which targeted therapies may be utilized either alone or in combination with other targeted therapies or chemotherapy to make a greater impact on treatment.

BREAST CANCER TARGETED THERAPY CLINICAL RESEARCH UPDATE

Hope S. Rugo, MD

The best way to utilize targeted agents in the management of patients with breast cancer can only be determined according to the results of carefully controlled clinical studies. This presentation will attempt to elucidate the optimal use of these new agents by addressing questions that oncology nurses eagerly want answered. The questions to be discussed will include:

Should trastuzumab be continued following disease progression?
Are there differences in clinical applications between trastuzumab and lapatinib?
Is incorporation of antiangiogenic agents standard in the treatment of metastatic breast cancer?
What new targeted agents are being evaluated in clinical trials?
Are certain chemotherapy regimens better than others in reducing cardiotoxicity when trastuzumab is used to treat early breast cancer?
In early breast cancer, does the schedule used for trastuzumab matter?
Is it worthwhile to recommend targeted therapy to those patients with early breast cancer who were treated only with chemotherapy?
Is there a role for lapatinib and bevacizumab in early stage breast cancer?
By using evidence-based data from carefully controlled clinical trials, these and other questions will be answered.

NURSING MANAGEMENT OF PATIENTS WITH BREAST CANCER RECEIVING TARGETED THERAPIES

Cheryl Casella-Rymer, ARNP, BC, MSN, OCN^®

As targeted therapies have become incorporated into the treatment paradigm for early stage and advanced breast cancer, nurses have become increasingly interested in their optimal use. Targeted therapies are associated with toxicities unique to specific agents. Recognition and timely management of these toxicities is critical in achieving optimal patient outcomes. This presentation will center on the discussion of answers to questions that have been submitted by oncology nurses during prior conferences. These questions pertain to procedures used to identify toxicities, administration guidelines, and what to do when toxicities are identified. The agents that will be discussed include trastuzumab, lapatinib, and bevacizumab.

Anti-HER2 agents have been associated with cardiotoxicity. Methods for early detection of cardiotoxicity will be discussed and recommendations based on algorithms will be made. The anti-vascular endothelial growth factor agent bevacizumab has been associated with the development of hypertension and proteinuria. The implications of these findings will be addressed. Toxicities associated with targeted agents may be disease specific. For example, the incidence of arterial thromboembolic events is significantly higher when bevacizumab is used in the treatment of colorectal cancer compared to breast cancer. Lapatinib, which has activity directed against epidermal growth factor receptor and HER2, is associated with rash and diarrhea. Some of these issues will be illustrated in the form of case presentations.