Abstract
Purpose: This study aimed to evaluate the prognostic impact of circulating tumor cells (CTC) detected in patients with operable or locally advanced breast cancer before and after neoadjuvant therapy (NT) within the clinical trial GeparQuattro.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 survival (DFS) and overall survival (OS) were analyzed by nonparametric Kaplan-Meier estimates and parametric Cox regression.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 P < 0.0001, respectively) and OS (P = 0.0057 and P < 0.0001, respectively), whereas 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 pathologic complete response (pCR) exhibited the best prognosis, whereas those with CTCs and less tumor response were at high risk of tumor relapse. In HER2 (ERBB2)-positive and triple-negative patients, ≥2 CTCs/7.5 mL detected before NT also were significantly associated with worse DFS and OS.Conclusions: 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. Clin Cancer Res; 23(18); 5384-93. ©2017 AACR.
Highlights
Therapeutic efficacy of neoadjuvant chemotherapy or targeted treatment for patients with breast cancer can be assessed rapidly without long follow-up periods [1, 2]
19) in blood samples taken before chemotherapy from 213 patients was significantly associated with worse disease-free survival (DFS) (P 1⁄4 0.031 and P < 0.0001, respectively) in univariate nonparametric Kaplan–Meier analysis (Fig. 1A and B)
circulating tumor cells (CTC) with both used cut-off values and absolute CTC counts detected after completion of chemotherapy were not significantly associated with DFS in the total patient cohort (1 CTC, P 1⁄4 0.43; 2 CTCs/ 7.5 mL (2 CTCs), P 1⁄4 0.69; Supplementary Fig. S1A and S1B)
Summary
Therapeutic efficacy of neoadjuvant chemotherapy or targeted treatment for patients with breast cancer can be assessed rapidly without long follow-up periods [1, 2]. The assumed better longterm benefit for patients that achieve a pathologic complete response (pCR) has led to the approval of new therapeutic approaches especially for this setting [1]. Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).
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