Abstract 1597: Increased circulating tumor cell (CTC) after systemic therapy is associated with younger age in stage III/IV breast cancer patients
Authors: Zhang Qiang , Gerratana Lorenzo , Flaum Lisa , Zhang Youbin , Gradishar William , Platanias Leonidas , Cristofanilli Massimo 
Published: August 2018

Introduction: Breast cancers (BCa) in younger women are more likely to be fast-growing, higher grade and hormone receptor-negative. As such these tumors tend to be associated with a worse prognosis even after systemic treatments with surgery, chemotherapy and radiation. The mechanisms that contribute to these tumors' aggressiveness remain largely unknown. Surveillance of circulating tumor cells (CTCs) may help to understand BCa prognosis and predict treatment benefit, especially for women with metastatic disease. Herein, we report a new finding of the correlation between age and the changes of CTC after the systemic therapies.

Methods: 160 whole blood samples (7.5ml/each) were collected from 100 patients with stage III/IV BCa at baseline, before and after systemic therapy. CTC enrichment and enumeration were performed in FDA approved semi-automated fluorescence CELLTRACKS ANALYZERII® System (Janssen Diagnostics) by using CELLSEARCH® CXC Kit (Cell Search). CTCs were confirmed using Anti-CK-PE, CD25, and EpCaM antibody and DAPI nuclear stain. Anti-CD45-APC antibodies were used to identify leukocytes. The CTCs were classified based on morphology and correct phenotype as CK+, EpCAM+, DAPI+ and CD25-. Database of CTCs was generated and linked with clinical database. Student test was used for statistics.

Results: Among 100 subjects who met inclusion criteria, 54 subjects (68%) at least 1 detectable CTCs in the baseline blood drawn prior to treatment. Of those, 37 patients had ≥ 5 CTCs, 17 patients had 1-5 CTCs, and 46 patients had no CTCs. There was no significant difference on the average age between these CTCs groups, which are 54.89, 53.52 and 53.30 respectively (P&gt;0.05). Among the initial cohort, 42 subjects had at least 2 blood draws before and after systemic therapies respectively. Among these 42 patients, 11 had more CTCs after systemic therapy [Group 1 (26%), the increased range of CTC is from 1 to 756] and 17 patients had no CTCs before or after therapy [Group 2 (40%)]. There were 14 patients who had significantly fewer CTCs after systemic therapy [Group 3 (34%), the decreased range of CTC is from -1 to -23]. There was a significant difference in the average ages of each group (48.45, 56.00 and 57.28 years respectively; P=0.02). The results indicated that younger age (less than 50 years old) is associated with persistent of higher CTCs after systemic therapy likely reflecting decreased benefit from systemic therapy.

Conclusion: Our original findings suggest age-related differences in CTCs response after systemic therapies for advanced BCa. These findings may indicate that younger patients may be at higher risk of developing more distant metastases as suggested by the increased numbers of CTCs after the systemic therapies. We propose that a combination of baseline CTCs detection and age be considered as a potential new criteria for selecting the systemic therapies for BCa patients.

Citation Format: Qiang Zhang, Lorenzo Gerratana, Lisa Flaum, Youbin Zhang, William Gradishar, Leonidas Platanias, Massimo Cristofanilli. Increased circulating tumor cell (CTC) after systemic therapy is associated with younger age in stage III/IV breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1597.