Abstract PD04-02: Clinical Value of Circulating Tumor Cells (CTC) in First Line Metastatic Breast Cancer (MBC) Patients (pts) According to Type of Treatment and Immunohistochemical Molecular Subtype

Abstract

Background: The detection of more than 5 CTCs/7.5 ml of blood in MBC pts predicts worse progression-free survival (PFS) and overall survival (OS). We investigated time-related clinical trend of CTCs according to types of 1st line therapy (hormonal therapy, HTx; chemotherapy CTx, anti-HER2 therapy; CTx with Bevacizumab) and immunohistochemical (IHC) subtypes of disease. Methods: Enumeration of CTCs was performed by the CellSearch™ technology as standard of care for 235 MBC pts receiving 1st line treatment for MBC. The evaluation of CTCs was performed as follow: baseline CTC value defined as assay taken within 30 days before starting therapy, post-treatment CTC value defined as the lowest CTC value after starting therapy; progression CTC value defined as assay taken within 30 days before documented radiological progression of disease (PD). We analyzed the effect of treatments on CTC count by Wilcoxon matched pair test and the progression CTC value within all subtypes by Kruskal-Wallis one-way analysis of variance. Results: A total of 1,052 CTC assays were performed from September 2004 to June 2010 in 235 MBC pts. One hundred thirty pts (55%) had HR+/HER2- MBC, 20 (9%) HR+/HER2+, 23 (10%) HR-/HER2-, and 62 (26%) triple-negative MBC (TNBC). Forty-seven pts received HTx (25 with available post-treatment CTC, median PFS for all group: 10.6 months), 41 pts were treated with anti-HER2 treatment (30 post-treatment CTC, median PFS: 12 months), 39 received Bevacizumab (31 post-treatment CTC, median PFS: 7.3 months), 87 CTx combination with taxanes/anthracyclines or other (epothilone or platinum salts) (57 post-treatment CTC, median PFS: 9.4 months) and 21 mono-chemotherapy (16 post-treatment CTC, median PFS: 3.6 months). Table 1 describes treatment distribution among subtypes. All administrated 1st line treatments decreased the CTC number with exception of HTx (66% patients decreased post-treatment CTCs value after HTx, p=.31). According to IHC subtypes, post-treatment CTC value decreased in all subtypes, while progression CTC at radiological PD increased in pts with HR+/HER2- and TNBC (45% and 51% pts had < 5 progressing CTCs, respectively, p<.05), but remained low in HER2+ subtypes (92% pts had < 5 progressing CTCs, p>.05). Conclusion: This large retrospective study showed that monitoring of CTCs is an appropriate tool for predicting response to different types of treatments, but is least useful for pts receiving HTx. Clinical trend of CTC value consistently reflects disease course in pts with HR+/HER2- and TNBC, while pts with HER2+ MBC treated with trastuzumab or lapatinib presented a low number of CTCs at PD. Our data may suggest phenotypical heterogeneity of CTCs in pts with HER-2 amplified and HR+ disease. Table 1 Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD04-02.

Serial enumeration of circulating tumor cells predicts treatment response and prognosis in metastatic breast cancer: a prospective study in 393 patients

“…as a noninvasive means of predicting and monitoring response to treatment in metastatic disease, has recently been comprehensively discussed by Alix-Panabieres and Pantel [ 25 ]. Unsuccessful regimens could be abandoned early in favor of alternative regimens, thus sparing patients unnecessary toxicity [ 6 - 8 ]. Moreover, in the future real-time CTC enumeration during therapy should be complemented by additional markers, which enable the monitoring of those cells which possess the highest metastasis-inducing activity within the highly heterogeneous pool of EpCAM+ CTCs [ 4 , 26 ].…”

“…In addition, the prognostic information of ≥ 5 CTCs/7.5 ml blood might be helpful in identifying those patients who would likely experience a worse outcome with standard treatment and might benefit from more aggressive therapy [ 4 ]. Thus far, several retrospective and a few prospective studies in patients with MBC have demonstrated the usefulness of monitoring therapeutic efficacy by serial CTC enumerations [ 6 - 9 ]. To further address this important issue, the present study aimed to prospectively assess in a large group of patients whether CTC status at baseline (CTC BL ) and after one cycle of a new line of treatment (CTC 1C ) and changes in CTC status from baseline to completion of one treatment cycle (CTC kinetics, CTC KIN ) could serve as early predictors of efficacy in terms of response, PFS, and OS.…”