ASCO 2023: Circulating tumor cells (CTCs) detection and isolation in different subtypes of early-stage breast cancer patients from Bangladesh.

Background

Breast cancer is a highly heterogeneous pathophysiology characterized by poor outcomes. Due to the increasing incidence and disease progression rates and undefined relapse periods, reliable disease monitoring is a challenge and has remained an unmet need. Advancements in liquid biopsy have significantly enhanced our understanding of clinical oncology. CTC-based liquid biopsy is emerging as a reliable prognostic tool to predict various clinical indicators. Although extensively investigated in metastatic breast cancers, little is known about CTCs in early-stage breast cancers. CTCs with respect to different molecular subtypes of breast cancer in early-stage breast cancer patients is evaluated.

Methods

In this prospective clinical trial (CMC 59.27.0000.013.19 PG.009.2022/262), 40 early-stage patients with luminal (A + B, 33.33%), HER2-positive (12.8%), triple-negative (12.8%), and undetermined (41.07%) subtypes were recruited. CTCs were isolated in 1.5 ml blood using the Drug Controller General of India approved OncoDiscover CTC test. This platform contains affinity-based magnetic nanoparticles to mediate EpCAM-based CTC isolation. CTCs were detected as CK18+, DAPI+, and CD45- cells using a fluorescence detection-based automated digital imaging platform.

Results

CTCs were detected in 60% of patients with a mean CTC count of 1 cell / 1.5 ml blood. Among total positive patients, the luminal subtype was the least positive (46%), followed by TNBC (60%) and undetermined (62.5%) subgroups, while all HER2-positive patients showed the presence of CTCs. Besides individual cells, CTC clusters were detected in 12.5% of patients, and they were equally distributed in luminal and HER2-positive subpopulations. When analyzed on the scale of tumor grade, grade I patients did not show the presence of CTCs, while 58.33% of grade II patients had ≥ 1 CTC. All grade III patients showed the presence of ≥ 1 CTC. CTC count was high among CTC-positive grade II patients (average 2 CTCs) and correlated well with the presence of CTC clusters in these patients. Patients who had surgical intervention had a low CTC burden compared to patients who did not have a surgical resection. 75% of treatment-naive patients showed the presence of CTCs, while 58% of patients receiving chemotherapy alone showed the presence of 1 CTC. 50% of patients who had surgery followed by CT + RT showed the presence of 1 CTC.

Conclusions

The presence of CTCs may suggest the biological progression of disease in early-stage BC patients. CTCs detected in all HER2-positive patients suggested the high shedding nature of these tumors, which correlates well with their reported migratory tendency. The presence of CTCs did not show a clear correlation with the treatment regimen. However, this data is based on a single time point and needs longitudinal correlation with CTCs on a larger sample size.

Clinical Trial Information

59.27.0000.013.19 PG.009.2022/262.