1. www.OncologyEducation.ca Five Year Update of Cardiac Dysfunction in NSABP B-31 A Randomized Trial of AC  Paclitaxel vs. AC  Paclitaxel with Trastuzumab in HER2- Postive, Node Positive, Operable Breast Cancer Authors: Rastogi et al. Reviewer: Dr Sunil Verma Date posted: June 21, 2007

2. www.OncologyEducation.ca R Treatment A: AC q3wk x 4 Paclitaxel q3wk x 4* or Paclitaxel qwk x 12* Treatment B: AC q3wk x 4 Paclitaxel q3wk x 4* Or Paclitaxel qwk x 12* + Trastuzumab qwk x 52 Operable breast\ cancer Her-2Positive tumour Pathological Positive Axillary nodes

3. www.OncologyEducation.ca RESULTS About 6.5% of patients randomized to the Herceptin containing arm did not receive Herceptin related to cardiac dysfunction with four cycles of AC 3 year data (previously reported) on Cardiac Events No herceptin0.8% Herceptin4.1% 5 year update (current presentation at ASCO 2007) No herceptin0.9% Herceptin3.8% The following factors were found to be predictive for cardiac toxicity Age Use of Hypertension medications LVEF

4. www.OncologyEducation.ca STUDY COMMENTARY This was a 5 year update on cardiac toxicity associated with Herceptin as per the NSABP B-31 Trial There doesn’t seem to be increased cardiac toxicity with longer follow-up There was a predictive model presented to better predict the risk of cardiac toxicity

5. www.OncologyEducation.ca BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS It is important to address modifiable cardiac risk factors prior to initiating therapy The risk of cardiac toxicity is dependent of many patient related factors It is prudent to review these factors in the context of tumor profile and make the decision on the need for Herceptin on an individual basis Long term follow up is still needed as most of these cardiac events may occur later We still don’t know the long term effect of asymptomatic LV dysfunction