R5洪逸平 SUPERVISOR 趙大中醫師 Breast Cancer The most prevalent cancer in female Mortality 4th 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 Circulating soluble-tumor–associated protein biomarkers Circulation tumor cells Circulating tumor DNA Radiologic image Expensive Time consuming Inconvenient Inconclusive May not informative in several months Reasonably sensitive, not always reflect tumor response or progression Standard serologic test Such as AST and ALT, LDH Inaccurate 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. Circulation tumor cells In 2004, pts with fewer CTC lived longer than with N Engl J Med 351(8):781–791. more CTC 177 Pts with metastatic breast cancer Annals of Oncology 22: 86–92, 2011 CTCs and tumor markers in Breast Cancer IC 2006-04 enrolled prospectively 267 metastatic breast cancer pts. Breast Cancer Research 2012, 14:R29 Circulation tumor DNA 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 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. 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 3kinase, catalytic subunit alpha protein) and TP53 (encoding tumor protein p53) or paired-end wholegenome sequencing p53 mutations are found in 50–75% of breast carcinoma patients Science (Wash. DC), 253: 49–53, 1991. Serial blood samples(30ml) every 3 or more weeks Identification of Genome Alteration Tagged-amplicon deep sequencing Paired-end whole-genome sequencing mutation 22 3 SV 5 CA 15-3 vs ctDNA CTCs and ctDNA Result Result Result Quartiles of ctDNA and OS ctDNA, CTCs and Relative Hazard 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… Future Target like BCR/ABL may be found and develop new target therapy!! Thanks for Your Attention!!