1. R5 洪逸平 SUPERVISOR 趙大中醫師

2. Breast Cancer  The most prevalent cancer in female  Mortality 4 th in Taiwan

3. Treatment of Breast Cancer

4. Breast Cancer  When to change regimen?  Unacceptable toxicity  Progression disease

5. Current Tools for Follow-up  Radiologic image  Standard serologic test  Circulating soluble-tumor–associated protein biomarkers  Circulation tumor cells  Circulating tumor DNA

6. Radiologic image  Expensive  Time consuming  Inconvenient  Inconclusive  May not informative in several months  Reasonably sensitive, not always reflect tumor response or progression

7. Standard serologic test  Such as AST and ALT, LDH  Inaccurate

8. Circulating soluble-tumor–associated protein biomarkers  CEA, CA 15-3  CA 15-3, soluble forms of MUC(cell surface associated )-1 protein J Clin Oncol 2007 25:5287-5312.

9. Circulation tumor cells  In 2004, pts with fewer CTC lived longer than with more CTC N Engl J Med 351(8):781–791. 177 Pts with metastatic breast cancer Annals of Oncology 22: 86–92, 2011

10. CTCs and tumor markers in Breast Cancer  IC 2006-04 enrolled prospectively 267 metastatic breast cancer pts. Breast Cancer Research 2012, 14:R29

11. Circulation tumor DNA

12. Circulating tumor DNA  In a study in China, 46 of 126 primary breast cancer pts have p53 mutation in the peripheral blood Clin Cancer Res 2001;7:2222-2227

13. Circulating tumor DNA  Specific mutation and structural variation in primary tumor cell  142 breast cancer pts ( not disseminated) was analyzed at diagnosis Clin Cancer Res 2002;8:3761-3766.

14. Method  Prospective, single-center study  Compare circulating tumor DNA, CA 15-3, circulating tumor cell  Tagged-amplicon deep sequencing for PIK3CA (encoding the phosphatidylinositol-4,5-bisphosphate 3- kinase, catalytic subunit alpha protein) and TP53 (encoding tumor protein p53) or paired-end whole- genome sequencing  p53 mutations are found in 50–75% of breast carcinoma patients  Serial blood samples(30ml) every 3 or more weeks Science (Wash. DC), 253: 49–53, 1991.

15. Identification of Genome Alteration  Tagged-amplicon deep sequencing  Paired-end whole-genome sequencing

16. 22 35 mutationSV

17. CA 15-3 vs ctDNA

18. CTCs and ctDNA

19. Result

23. Quartiles of ctDNA and OS

24. ctDNA, CTCs and Relative Hazard

25. Conclusion  Circulating tumor DNA shows superior sensitivity and has a greater dynamic range that correlates with tumor burden  Circulating tumor DNA provide earliest measure of treatment response  Identification of somatic alteration is needed  Target sequencing could be expanded in addition to PIK3CA and TP53 when the cost reduced  There are many ways to identify tumor DNA : digital PCR assay, targeted deep sequencing, exome sequencing, BEAMing, Safe-SeqS…

26. Future  Target like BCR/ABL may be found and develop new target therapy!!

27. Thanks for Your Attention!!