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Breast Cancer Journal Club

Vol. 5, No. 2
1 AMA PRA Category 1 Credit^™

Release date: May 6, 2008
Expiration date: May 6, 2009

Table of Contents

A Phase III Randomized Comparison of Lapatinib Plus Capecitabine Versus Capecitabine Alone in Women With Advanced Breast Cancer That Has Progressed on Trastuzumab: Updated Efficacy and Biomarker Analyses
Cameron D et al. Breast Cancer Res Treat; January 11, 2008 [e-pub ahead of print].

Cardiac Safety Analysis of Doxorubicin and Cyclophosphamide Followed by Paclitaxel With or Without Trastuzumab in the North Central Cancer Treatment Group N9831 Adjuvant Breast Cancer Trial
Perez EA et al. J Clin Oncol 2008; 26:1231-8.

Phase II Study of Predictive Biomarker Profiles for Response Targeting Human Epidermal Growth Factor Receptor 2
(HER2) in Advanced Inflammatory Breast Cancer With Lapatinib Monotherapy Therapy
Johnston S et al. J Clin Oncol 2008; 26:1066-72.

Combination of Trastuzumab and Tanespimycin (17-AAG, KOS-953) Is Safe and Active in Trastuzumab-Refractory HER2-Overexpressing Breast Cancer: A Phase I Dose-Escalation Study
Modi S et al. J Clin Oncol 2007; 25:5410-17.

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2. Study the educational activity.
3. Complete the CME test.
4. Answer the evaluation questions.
5. After successful completion of the CME test and evaluation, you will receive your certificate of credit online.

• The CME test and evaluation must be completed by May 6, 2009, in order to receive your certificate of credit.
• CME credit will be granted for only 1 form of participation, either online or via the printed publication.

Recent advances in breast cancer therapy are largely due to the development of targeted therapies, particularly agents targeting the ErbB2 receptor. ErbB2-targeted agents have demonstrated efficacy in both the adjuvant and metastatic settings, but risk of cardiac toxicity has been a concern. Longer follow-up in the adjuvant setting and the identification of cardiac toxicity risk factors allows better understanding of risk:benefit ratios. A majority of patients with ErbB2⁺ metastatic disease eventually develop resistance to current first-line ErbB2-targeted therapy, leading to investigation of alternative therapeutic strategies, such as small-molecule ErbB2 tyrosine kinase and heat shock protein (HSP)90 inhibitors that enhance the degradation of ErbB2 and other signaling molecules critical to tumor cell function. Research is focused on the identification of predictive biomarkers that aid in patient selection and investigation of regimens combining these agents with traditional cytotoxic or other targeted biologic agents. ErbB2-targeted agents are also being evaluated in the treatment of inflammatory breast cancer.

The purpose of this activity is to provide medical oncologists with the latest information on the use of targeted therapeutic strategies in ErbB2⁺ early-stage or metastatic breast cancer and inflammatory breast cancer as well as the identification of markers of benefit and risk for these therapies.

• Assess the utility of serum epidermal growth factor receptor and ErbB2 extracellular domain levels to predict benefit from
  therapy with small-molecule ErbB2 tyrosine kinase inhibitors in combination with oral fluoropyrimidines in the treatment of
  relapsed/refractory advanced breast cancer
• Evaluate the cardiac toxicity and cardiac risk factors associated with the addition of ErbB2-targeted therapy to chemotherapy in patients with ErbB2⁺ early-stage breast cancer
• Discuss the safety and efficacy of ErbB2-targeted therapy for recurrent/refractory inflammatory breast cancer
• Discuss the safety and efficacy of HSP90 inhibitors in combination with ErbB2-targeted agents in patients with relapsed/refractory ErbB2⁺ metastatic breast cancer

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