Effect of circulating tumor cells distribution in treatment naive and treated patients with advance stage breast cancer on disease burden.
Authors: Khandare Jayant , Raut Nirmal Vivek , Aland Gourishankar , Garbhe Meghana , Gosavi Sayali , Janorkar Apoorva , Khutale Ganesh , Patil Mrunmayi , Ashturkar Amrut , Jadhav Vikas Balasaheb Leelavati , D'Souza Alain , Tulpule Varun , Kothavade Hrishita , Tiwari Priya , Vasudevan Aravindan , Jayant Sreeja , Bharde Atul 
Published: June 2023

e12517

Background: Breast malignancies is a leading cause of cancer-related mortalities and show ascending incidence rate. Despite advancements in our understanding of the disease, its clinical outcome is often dismal. This largely remains owing to the characteristic wide window of relapse, spanning months to decades after primary treatment. Therefore, continuous monitoring of the disease is an offered choice to detect metastatic progression and recurrence. Circulating tumor cells (CTCs) have emerged as a powerful prognostic tool to predict the disease outcome in many epithelial cancers. CTCs are a real-time surrogate biomarker accounting for minimal residual disease (MRD) which is often missed in CT PET scanning. This leads to a progression of metastasis when the patient is often considered as ‘clinically disease free’. Here, we analyzed the presence of CTCs in treatment-naïve and chemo-recipient breast cancer patients. Methods: In this retrospective study on 417 breast cancer patients, CTCs were isolated from 1.5 ml of blood using the Drug Controller General of India (DCGI) 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 based on automated digital imaging platform. Results: 42.6 % (n=178) of patients were clinically at progressive stage (stage II and III) and treatment naïve. On the other hand, 47.4 % of patients received treatment including surgery and chemotherapy. CTCs were not observed in 5.6 % (n=10) of the treatment naïve population while 32% (n=75) of patients who received therapy did not show CTCs. The mean CTC number in treatment naïve patients was 15, while the mean CTC count in patients receiving therapy was drastically reduced to 2. This implied that therapy effectively countered the tumor progression and reduced the shedding of tumor cells in circulation. The distribution of CTC in treatment naïve patients exhibited a bimodal trend centered at values of 10 and 50, suggesting two distinct populations of patients with respect to CTC count. CTC count did not show any correlation with the age in both population groups. Surprisingly CTC count in younger patients (20-50 years) was 50% higher compared to the older population (50-75 years). Conclusions: The presence of CTCs in treatment naïve, progressive breast cancer patients indicated the biologically aggravated disease. Although therapeutic intervention drastically reduced the CTC burden, their presence in a large population was suggestive of an MRD and the likelihood of recurrence after discontinuation of therapy. A distinct pattern of CTC occurrences in Tx naïve and Tx recipient patient suggested that CTCs can be an important clinical indicator to monitor the therapy response, progression and residual disease.