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R5 洪逸平 SUPERVISOR 趙大中醫師

R5 洪逸平 SUPERVISOR 趙大中醫師. Breast Cancer. The most prevalent cancer in female Mortality 4 th in Taiwan. Treatment of Breast Cancer. Breast Cancer. When to change regimen? Unacceptable toxicity Progression disease. Current Tools for Follow-up. Radiologic image Standard serologic test

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R5 洪逸平 SUPERVISOR 趙大中醫師

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  1. R5洪逸平SUPERVISOR 趙大中醫師

  2. Breast Cancer • The most prevalent cancer in female • Mortality 4th 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 ClinOncol 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-amplicondeep 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-amplicondeep sequencing • Paired-end whole-genome sequencing

  16. mutation SV 22 3 5

  17. CA 15-3 vsctDNA

  18. CTCs and ctDNA

  19. Result

  20. Result

  21. Result

  22. Quartiles of ctDNA and OS

  23. ctDNA, CTCs and Relative Hazard

  24. 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, exomesequencing, BEAMing, Safe-SeqS…

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

  26. Thanks for Your Attention!!

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