Abstract P2-02-02: Differences in levels of circulating tumor cells (CTC) and disseminated tumor cells (DTC) in early-stage lobular versus ductal breast cancer
Authors: Alkhafaji Silver , Wolf Denise , Magbanua Mark , Van 't Veer Laura , Park John , Esserman Laura J. , Mukhtar Rita A. 
Published: March 2022

Abstract
Background: Invasive lobular carcinoma (ILC) is the second most common type of breast cancer after invasive ductal carcinoma (IDC). ILC has unique features, such as a diffuse growth pattern due to characteristic loss of E cadherin, and a different pattern of disease metastasis compared to IDC. Prior investigators have shown increased numbers of circulating tumor cells (CTCs) in patients with metastatic ILC versus IDC. We explored the distribution of CTCs and disseminated tumor cells (DTCs) in early stage ILC versus IDC. Methods: We performed a secondary data analysis of the TIPPING study, an institutional review board approved study that pre-operatively collected blood and bone marrow samples from 655 treatment-naïve early-stage breast cancer patients. We analyzed data from 284 patients who had CTCs and DTC enumerated by an EPCAM-based method involving immunomagnetic enrichment and flow cytometry (IE/FC) (61 patients with ILC and 223 patients with IDC). We compared CTC and DTC counts by histology using the Welch Two Sample t-test, linear regression models, as well as ANOVA tests. Multivariate Cox regression analyses were performed to assess association between levels of CTCs/DTCs and clinical outcomes (distant recurrence-free survival [DRFS] and breast cancer-specific survival [BCSS]). Results: ILC tumors were lower grade than IDCs and had a higher proportion of HR+HER2- subtypes (92.00% vs. 75.30%; p&lt;0.001). ILC patients had significantly higher CTC counts than IDC patients (mean 2.11 vs. 0.71 CTCs/mL; p&lt;0.001), a difference that retained significance after adjusting for clinical variables (p=0.003). Additionally, we identified a subset of ILC patients (n = 9; 14.75%) that have elevated CTCs, which was absent in the IDC subset. ILC patients with elevated CTC levels showed no statistically significant association between CTC as a continuous variable with nodal status and breast cancer stage (p=0.26, p=0.25, respectively). In our study, the overall median follow-up was 7.26 years for DRFS and 8.9 years for BCSS. In the subset of ILC patients with elevated CTCs, CTC level as a continuous variable did not show significant association with DRFS or BCSS in a multivariate model adjusting for clinical variables. In the IDC subset, CTC level as a continuous variable did not show significant association with DRFS or BCSS in a multivariate model adjusting for clinical variables.Furthermore, there was no difference in the number of DTCs in ILC versus IDC. DTC level as a continuous variable did not show significant association with DRFS or BCSS in a multivariate model adjusting for clinical variables in both ILC and IDC subsets. Conclusions: Early-stage ILC patients have significantly higher CTC levels than those observed in IDC patients, and we hypothesize that the reason may be due to lower cell-cell adhesion. ILC spans the spectrum of indolent (benign) to high risk (bad actor) disease. Thus, biomarkers like CTCs may allow us to identify ILC patients who are at higher risk of late recurrence and make appropriate therapeutic decisions at earlier point in time. Studies like Endocrine Optimization Pilot in I-SPY 2 are ongoing to further investigate the use of biomarkers like CTCs to inform outcomes. Due to the short follow-up period, we will conduct an additional follow-up which should give us 10 years of follow-up, which is likely needed due to the risk for late recurrence in ILC patients.
Citation Format: Silver Alkhafaji, Denise Wolf, Mark Magbanua, Laura Van 't Veer, John Park, Laura J. Esserman, Rita A. Mukhtar. Differences in levels of circulating tumor cells (CTC) and disseminated tumor cells (DTC) in early-stage lobular versus ductal breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-02-02.