Abstract P2-02-21: The utility and correlation of circulating tumor cells (CTCs) and cell-free circulating tumor DNA (ctDNA) based on HER2 positivity
Authors: Davis AA , Zhang Y , Behdad A , Taxter T , Strickland K , Santa-Maria C , Flaum L , Cruz MR , Platanias LC , Gradishar WJ , Cristofanilli M 
Published: February 2018

Background:

CTCs are well-established prognostic and predictive biomarkers for metastatic breast cancer (MBC) and other solid tumors. ctDNA is emerging as a quantitative blood-based biomarker for monitoring genomic alterations and disease progression. We evaluated the clinical utility and correlation of these liquid biopsy molecular tools in a cohort of MBC patients.

Methods:

CTC samples were obtained from an ongoing, prospective study of blood based prognostic biomarkers for breast cancer patients. At this time, 71 patients and 98 total samples have been collected. CTC enumeration was performed using the CellSearchTM platform (Menarini, IT). Within this cohort, MBC patients who had ctDNA testing were identified. ctDNA testing was performed using Guardant360TM (Guardant Health, CA), a digital next-generation sequencing technology. Two groups were analyzed: (1) HER2-negative patients with CTC ≥ 5 in 7.5 ml of blood (2) HER2-positive patients who had been treated with HER2 targeted therapy.

Results:

22 samples (N=16 patients) were found with CTC ≥ 5 (range 8-904) and concurrent ctDNA testing (median timeframe between collection 0 days, range 0-42 days). There was a significant association between number of CTCs and the total number of genomic alterations detected in ctDNA (paired two sample t-test, p=0.012). In addition, CTC enumeration was significantly correlated with somatic alteration burden of the dominant clone (paired two sample t-test, p=0.023). The most common alterations detected in the blood were TP53 (55% of patients, 18 total mutations), PIK3CA (41% of patients, 15 total mutations), and ESR1 (32% of patients, 14 total mutations). For patients with HER2 positivity receiving HER2-targeted therapies (N=16 samples from 11 patients), only 18.8% of samples had detectable CTCs (all less than 5) as compared to 75.0% of samples with detectable ctDNA alterations. In N=12 samples with detectable ctDNA mutations, mean number of genomic alterations was 4.4 with mean somatic mutation burden of 2.95%.

 CTCs detectedctDNA detectedCTC ≥ 5Mean number of ctDNA alterations+Mean somatic alteration burden+HER2- (only cases with CTC ≥ 5)100% (22/22)100% (22/22)100%6.716.1%HER2+ (all cases)18.8% (3/16)75.0% (12/16)0%4.42.95%+excludes ctDNA samples without detected genomic alterations

Conclusions:

In HER2-negative MBC patients, CTC enumeration was significantly correlated with the number of ctDNA genomic alterations and somatic alteration burden, indicating the potential for ctDNA as a prognostic, quantitative biomarker of tumor burden. In patients with HER2 positivity, ctDNA may be a more sensitive liquid biopsy tool given the rarity of detecting CTCs detection in this population using the CellSearchTM system. In HER2-positive patients, consideration of size-dependent selection of CTCs using filtration of cells that have undergone epithelial-mesenchymal transition may improve detection in this subgroup.

Citation Format: Davis AA, Zhang Y, Behdad A, Taxter T, Strickland K, Santa-Maria C, Flaum L, Cruz MR, Platanias LC, Gradishar WJ, Cristofanilli M. The utility and correlation of circulating tumor cells (CTCs) and cell-free circulating tumor DNA (ctDNA) based on HER2 positivity [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-02-21.