1. The 70-Gene Profile and Chemotherapy Benefit in 1,600 Breast Cancer Patients Bender RA et al. ASCO 2009; Abstract 512. (Oral Presentation)

2. Source: Bender RA et al. ASCO 2009; Abstract 512. Introduction Gene expression profiling has enabled assignment of risk profiles for patients with early-stage breast cancer (BC) not easily achieved using clinicopathologic variables 70-gene signature predicts 10-yr distant metastases-free survival (DMFS) [J Natl Cancer Inst 2006;98(17):1183] –Low risk: 90%; High risk 71% 70-gene signature predicts pathologic complete response to neoadjuvant chemotherapy (Breast Cancer Res Treat 2009 Feb 13 Epub ahead of print) –Low risk: 0%; High risk: 20% Current study objectives: –Pooled meta-analysis including patients from 7 large data sets at multiple institutions across Europe (N = 1,696) –Analyzed 541 patients with 0-3 involved lymph nodes who received endocrine therapy (ET) or ET plus chemotherapy (ET + CT)

3. Patients Treated with Adjuvant ET or ET + CT 7 Clinical Studies in the Meta-Analysis No. of Patients (n = 1,696) 0-3 Lymph Nodes Involved (n = 541) * Van de Vijver 200229530 Buyse 20063020 Bueno-de-Mesquita 2007427182 Bueno-de-Mesquita 200812329 Mook 2008a241154 Mook 2008b14827 Kok 2009160119 Source: Bender RA. ASCO 2009; Abstract 512. *Abstract included 575 patients, including all lymph node positive disease; here patients with >3 nodes excluded

4. 100 0 80 60 40 20 0 12345 Distant Disease-Free Survival (DDFS) of Treated Patients as a Function of 70-Gene Risk Profile (MammaPrint) Source: With permission from Bender RA. ASCO 2009; Abstract 512. Low risk (n=252, 47%) High risk (n=289, 53%) HR 3.88 (1.99-7.58) P<0.01 95% 82% Percent Survival Time in years

5. 100 0 80 60 40 20 0 12345 DDFS in Patients Receiving ET vs ET + CT MammaPrint Low Risk (n = 252) ET (n=174, 69%) ET+CT (n=78, 31%) HR 0.26 (0.03-2.02) P=0.20 Time in years 99% 93% Source: With permission from Bender RA. ASCO 2009; Abstract 512. Percent Survival

6. 100 0 80 60 40 20 0 12345 DDFS in Patients Receiving ET vs ET + CT MammaPrint High Risk (n = 289) Time in years ET (n=141, 49%) ET+CT (n=148, 51%) 88% 76% HR 0.35 (0.17-0.71) P<0.01 Source: With permission from Bender RA. ASCO 2009; Abstract 512. Percent Survival

7. Summary and Conclusions Patients with a “low risk” 70-gene profile are at sufficiently low risk of developing distant metastases that adjuvant CT appears to add no benefit to ET alone Patients with a “high risk” profile are at high risk of developing distant metastases and are likely to benefit from the addition of CT to ET MINDACT, the ongoing prospective randomized clinical trial in Europe, is assessing the benefit of treatment assignment, based on gene expression profiling instead of conventional clinicopathologic risk assessment Source: Bender RA et al. ASCO 2009; Abstract 512.

8. Eligibility: T1, T2 or operable T3 invasive breast cancer; 0-3 positive nodes; unilateral tumor Target accrual: 6,000 Evaluate for clinical-pathological risk (using Adjuvant! Online) AND 70-gene signature risk (using MammaPrint ® ) Clinical high risk, genomic high risk Discordant risk between standard clinical- pathological and 70-gene signature criteria Clinical low risk, genomic low risk Chemotherapy No chemotherapy Use clinical- pathological risk results to determine chemotherapy or not Use 70-gene risk results to determine chemotherapy or not Source: Cardoso F et al. J Clin Oncol 2008;26(5):729-735. MINDACT: Comparison of 70-Gene Signature with Clinical Assessment in Selecting Patients with Node-Negative Breast Cancer for Adjuvant Chemotherapy R