Prognostic impact of circulating tumor cells for breast cancer patients treated in the neoadjuvant "Geparquattro" trial

Purpose: This study aimed to evaluate the prognostic impact of circulating tumor cells (CTCs) detected in patients with operable or locally advanced breast cancer before and after neoadjuvant therapy (NT) within the clinical trial GeparQuattro.<br />Experimental Design: Data on CTCs enumerated with the CellSearch™ system were available for 213 and 207 patients before and after NT, respectively. Associations of CTCs with disease-free (DFS) and overall survival (OS) were analyzed by non-parametric Kaplan-Meier estimates and parametric Cox regression.<br />Results: After a median follow up of 67.1 months, the detection of ≥1 CTC/7.5 mL and ≥2 CTCs/7.5 mL before NT was associated with reduced DFS (p=0.031 and <0.0001, respectively) and OS (p=0.0057 and p<0.0001, respectively), while CTCs detected after NT did not correlate with DFS or OS. In parametric univariate and multivariate Cox models, ≥1 CTC/7.5 mL, ≥2 CTCs/7.5 mL and absolute CTC numbers before NT revealed to be independent prognostic parameters of DFS and OS. CTC-negative patients with pathological complete response (pCR) exhibited the best prognosis, while those with CTCs and less tumor response were at high risk of tumor relapse. In HER2-positive and triple negative patients ≥2 CTCs/7.5 mL detected before NT also were significantly associated with worse DFS and OS.<br />Conclusion: Detection of CTCs before NT is an independent prognostic factor of impaired clinical outcome and combined with pCR it could be helpful to stratify breast cancer patients for therapeutic interventions.

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