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551 Background: Neoadjuvant chemotherapy (NCT) is the standard treatment for patients with locally advanced breast cancer (LABC). Liquid biopsy, including circulating tumor cells (CTCs) and cell free DNA (cfDNA) represent an important paradigm shift in precision medicine. The aim of this study was to estimate the value of CTCs and cfDNA in efficacy prediction of the response to NCT in patients with LABC. Methods: Patients with LABC received EC4-T4 regimen NCT. CTCs and cfDNA obtained at time of biopsy, after first course of NCT and after the last course of NCT. All patients were divided into two groups according to pathological reactivity. A novel SE-iFISH strategy, improved for detection of CTCs, was applied. CTCs(CD45-/CD31-) with different cytogenetic abnormality of aneuploid chromosome 8 and small cell size CTCs (≤5 mm of WBCs) were analyzed separately in LABC patients subjected to NCT for the first time. Plasma DNA biomarkers ALU 111 and ALU 260 elements were evaluated using qRT-PCR. DNA integrity was calculated relative to the breast cancer cell line MCF-7. Clinical significance of diverse subtypes of CTCs and cfDNA was systematically investigated. Results: A total of 45 patients was enrolled in this study. According to the therapy response, 6/45 patients had high response (High-R) and 39/45 patients had low response (Low-R). There were no significant differences in CTC number and small cell size CTC number between High-R and Low-R groups in all three detections. However, the CTC number kept stable in the High-R group, but increased continually during NCT in Low-R group. In 45 patients, the percentage of CTCs with trisomy 8, which were related to cancer metastasis, incresed in the Low-R group at the third dectection. The concentration of cfDNA in all three detections did not indicate outcome of NCT. However, concentration of ALU 111 increased in Low-R patients during NCT. In High-R patients, no significant increase was observed. A CTC and cfDNA panel were constructed to discriminate High-R patients from Low-R patients. The areas under the receiver-operating characteristic (ROC) curves of the pannel for the three times were 0.803, 0.859 and 0.667, respectively. DNA integrity index(CFDI) was significantly higher in High-R group than Low-R after first course of NCT. The areas under the ROC curves of the CFDI for the three times were 0.675, 0.863 and 0.697, respectively. Conclusions: The trend of cfDNA concentration changed resembled to the number of CTCs, small cell size CTCs and triploid CTCs during NCT, and could predict tumor response to ongoing treatment.
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