1. Metastatic Breast Cancer: One Size Does Not Fit All Clifford Hudis, M.D. Chief, Breast Cancer Medicine Service MSKCC

2. Breast cancer is predictable but not absolutely.

3. Invasive Ductal Carcinoma

4. Message Pathways Inside Cancer Cells

5. We define invasive breast cancer on the basis of 2 genes: ER and HER2

6. ER Negative

7. HER2 Positive

8. HER2/neu FISH Test

9. Outcomes are widely variable.

10. We have to consider the genome of the tumor AND the patient.

12. Cytoskeleton genes (n=641) Apoptosis genes (n=641)

13. HER- 2+/ER- Luminal A Luminal B Normal Sorlie T et al, PNAS 2001 Basal-like Five Kinds Of Breast Cancer?

14. Challenges Molecular profiles are: –Variable by population studied –Poorly adapted for clinical use –Biology as yet not well characterized –Relationship to conventional chemotherapy response not well characterized –Ability to correctly identify molecular targets not yet proven

15. Unsupervised Cluster Analysis of 99 primary breast carcinomas from MSKCC tumor bank

16. Class AClass B ALCAM p=0.023 SPDEF p<0.0001 AR p=0.04 IHC for differentially expressed genes in ER(-) Class A p<0.0001 ALCAM p<0.0001 AR SPDEF p<0.0001 AB B B A A Class A Class B

17. Real World - Now Your doctor makes an educated guess about the pace of the disease and treats accordingly. You and your doctor regularly assess the benefits of specific treatments and adjust accordingly

18. Real World - Future Your doctor tests your cancer AND your normal cells. You and your doctor rationally select therapy predicted to control or cure the disease.

19. Breast Cancer Medicine Service, MSKCC: 2005