Abstract 504: Circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) are superior to CA 15-3 in predicting tumor burden, patients response to treatment and overall survival (OS) rates in metastatic breast cancer patients from Egypt

Abstract

Background: Monitoring of tumor burden in patients with metastatic breast cancer (mBC) is crucial to determine response to treatment. In addition to radiological procedures and serological biomarkers, circulating, tumor cells (CTCs) are now used to assess the tumor burden and patients’ response to treatment. The circulating cell-free tumor DNA (ctDNA) harboring tumor-specific aberrations has not been properly assessed yet.

Methods: 100 Egyptian patients with locally mBC were assessed for CA 15-3 levels, CTCs number by flowcytometry (FCM) confirmed by RT-PCR (CK and mammaglobin expression), and for ctDNA. The results of the three techniques were compared to the radiographic imaging of tumors, patients response to treatment and overall survival (OS) rates. Paraffin blocks for 40 tumor samples, obtained from the studied patients (20 non-responders and 20 responders) were used to detect p53 gene mutations exons 5-9. CA 15-3 levels and CTC numbers were measured at the same time intervals.

Results: Somatic mutations of p53 were detected in 23/40 (57.5%) sequenced tumors. ctDNA showing the identified mutations in tumor samples, was detected in 78 cases (78%) with high dynamic range. CTCs>4/7.5ml blood were present in 57 out of the 78 (73.1%) ctDNA positive cases, and CA 15-3 was detected in 30 (38.5%) cases. Changes in ctDNA levels and CTCs>4 correlated significantly with the tumor burden (p = 0.034), patients response to treatment (p<0.01), and lower OS rates (p = 0.034&p = 0.01; respectively). CTCs number and ctDNA levels showed higher correlation with changes in tumor burden, compared to CA 15-3 (p<0.001 versus p = 0.046). However, ctDNA provided the earliest measure of treatment response in most of the patients (53%).

Conclusions: ctDNA is an informative, highly sensitive and specific biomarker that could be used to monitor tumor burden in mBC. Together with enumeration of CTCs they can predict tumor response and OS in mBC patients with high accuracy.

Citation Format: Abdel-Rahman N. Zekri, Abeer A. Bahnassy. Circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) are superior to CA 15-3 in predicting tumor burden, patients response to treatment and overall survival (OS) rates in metastatic breast cancer patients from Egypt. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 504.