1. Trials of Adjuvant Trastuzumab in HER2+ Early-Stage Breast Cancer Trial Study Regimen No. of Patients Disease-Free Survival (%) Hazard Ratio P-Value Overall Survival Hazard Ratio (%) P- Value NSABP B-31 and NCCTG N-9831 Doxorubicin and cyclophosphamide, then paclitaxel 16796787 Doxorubicin and cyclophosphamide, then paclitaxel plus trastuzumab, then trastuzumab 1672850.48<.001910.67.02 NCCTG N-9831 Doxorubicin and cyclophosphamide, then paclitaxel 979 Doxorubicin and cyclophosphamide, then paclitaxel, then trastuzumab 9850.87.290.85.48 Doxorubicin and cyclophosphamide, then paclitaxel plus trastuzumab, then trastuzumab 840 0.64.48.01 <.01 0.74.27 HERAObservation16987490 Trastuzumab for 1 year 1703810.64<.001920.66.011 BCIRG 006 Doxorubicin and cyclophosphamide, then docetaxel 10737386 Doxorubicin and cyclophosphamide, then docetaxel plus trastuzumab, then trastuzumab 1074840.49.001920.59.004 Docetaxel, carboplatin, and trastuzumab 1075800.61<.01910.66.02 FinHerChemotherapy1167890 Chemotherapy plus trastuzumab 116890.42.01960.41.07 With permission from Hudis CA. N Engl J Med. 2007;357:39-51.

2. ALTTO Formerly Known as APHRODITE Randomize Trastuzumab x 1 year Lapatinib x 1 year + lapatinib x 1 year Trastuzumab x 1 year Inclusion Criteria HER2+ breast cancer ≥4 cycles anthracycline-based neoadjuvant chemotherapy LVEF ≥50% Clinicaltrials.gov. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00490139?term=A. Accessed on: September 15, 2009. ALLTOTRIALS.COM—Trial Overview. Available at: http://www.alttotrials.com/patients.php#5. Accessed on: September 15, 2009. Trastuzumab x 12 weeks Break 6 weeks Lapatanib x 34 weeks

3. Targeting HER2+ Tumors With permission from Burstein HJ. N Engl J Med. 2005;353:1652-1654. Inhibit Kinase Activity Inhibit Dimerization Moderate Receptor Expression Potentiate Downstream Effects Refine Antibodies

4. Mechanism of Cell Death from Inhibition of Polyadenosine Diphosphate-Ribose Polymerase 1 (PARP-1) With permission from Iglehart JD, et al. N Engl J Med. 2009;361:189-191.

5. Radiologic Evidence of Tumor Response to Olaparib With permission from Fong PC, et al. N Engl J Med. 2009;361:123-134. Patient 20 at Baseline Patient 41 at Baseline Patient 20 at 4 Months Patient 41 at 4 Months A

6. Bevacizumab Summary of Breast Cancer Studies Median Progression-Free Survival Study Chemotherapy Chemotherapy + BevacizumabP-Value Miller 1 (capecitabine ± bevacizumab) 4.17 months4.86 monthsP =.857 AVADO 2 (docetaxel ± bevacizumab) 8.0 months 9.0 months with 7.5 mg/kg bevacizumab 10.0 months with 15 mg/kg bevacizumab P =.0164 P =.0002 E2100 3 (paclitaxel ± bevacizumab) 5.9 months11.8 monthsP <.001 RIBBON-1 4 (taxane/anthracycline ± bevacizumab) 8.0 months9.2 monthsP <.0001 RIBBON-1 4 (capecitabine ± bevacizumab) 5.7 months8.6 monthsP =.0002 1. Miller KD, et al. J Clin Oncol. 2005;23:792-799. 2. Miles D, et al. 44th ASCO; May 30-June 3, 2008. Abstract LBA1011. 3. Miller K, et al. N Engl J Med. 2007;357:2666-2676. 4. Robert NJ, et al. 45th ASCO; May 29-June 2, 2009. Abstract 1005.

7. VEGF Signaling Pathway in Angiogenesis With permission from Kerbel RS. N Engl J Med. 2008;358:2039-2049.

8. NSABP B-20 Outcome by Recurrence Score With permission from Paik S, et al. J Clin Oncol. 2006;24:3726-3734. Overall Intermediate risk: 18–30 Low risk: <18 High risk: >30

9. Oncotype DX recurrence score tends to correlate with established breast cancer prognostic/ predictive factors Oncotype DX recurrence score tends to correlate with established breast cancer prognostic/ predictive factors –Age –Tumor grade –HER2 –Quantitative ER/PR levels –Tumor size The “poor man’s” Oncotype DX The “poor man’s” Oncotype DX –TN stage, grade, ER, PR, HER2 Oncotype DX, Breast Cancer Assay. Available at: www.oncotypedx.com. Accessed on: September 14, 2009. Oncotype DX Breast Cancer Assay

10. Multigene Arrays and Prediction of Relapse-Free Survival in Breast Cancer With permission from Fan C, et al. N Engl J Med. 2006;355:560-569.