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  • 1
    Abstract: The detection of circulating tumor cells (CTCs) in the peripheral blood of metastatic breast cancer (MBC) patients is an independent marker of prognosis. This large prospective multicenter study aimed to assess the impact of CTCs on overall survival (OS) and progression free survival (PFS) in patients with predefined molecular subgroups of MBC. To this end, 468 MBC patients were divided into three subgroups based on immunohistochemical staining of the primary tumor: (1) hormone receptor-positive/HER2-negative (HorR+/HER2-), (2) HER2-positive (HER2+), and (3) HorR-negative/HER2-negative (HorR-/HER2-) patients. CTC status (〈5 CTCs/7.5 ml blood (CTC-negative) vs. 〉/=5 CTCs/7.5 ml blood (CTC-positive)) was determined using the CellCearch((R)) system before patients started a new line of therapy. At baseline, 205 (42 %) patients were CTC-positive. On multivariate analysis, CTC-positivity was an independent prognostic factor for shorter PFS and OS. In HorR+/HER2- patients, median PFS [95 % CI] of CTC-negative versus CTC-positive patients was 8.60 [5.93-11.27] versus 4.33 [3.29-5.38] months (p 〈 0.001), in HER2+ patients 7.60 [5.40-9.79] versus 6.60 [4.20-9.00] months (p = 0.477) and in HorR-/HER2- patients 5.83 [5.09-6.78] versus 3.05 [1.81-4.29] months (p 〈 0.001), respectively. Median OS [95 % CI] of CTC-negative versus CTC-positive patients was as follows: not reached by either in the HorR+/HER2- subgroup (p 〈 0.001), not reached versus 18.07 [11.10-25.05] months (p = 0.001) in the HER2+ subgroup, and not reached versus 8.57 [4.07-13.07] months in the HorR-/HER2- subgroup (p = 0.001). In conclusion, our results strongly confirm the independent prognostic value of CTC enumeration in MBC patients. In contrast to recent reports, there was no association between primary tumor-based molecular subgroups and the impact of CTC status on OS. Hence, CTC status may help to identify patients who require aggressive therapy, especially among those with triple-negative MBC.
    Type of Publication: Journal article published
    PubMed ID: 23271327
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  • 2
    Abstract: BACKGROUND: To prospectively assess circulating tumor cell (CTC) status at baseline (CTCBL) and after one cycle of a new line of systemic therapy (CTC1C), and changes from CTCBL to CTC1C (CTC kinetics, CTCKIN) for their utility in predicting response, progression-free (PFS) and overall survival (OS) in metastatic breast cancer (MBC). METHODS: CTCBL and CTC1C status was determined as negative (-) or positive (+) for 〈 5 or 〉/= 5 CTCs/7.5 ml blood using CellSearch (Veridex). CTCKIN was categorized as favorable (CTC1C-) or unfavorable (CTC1C+). Tumor response was to be assessed every 2-3 months using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Statistical analysis focused on the relation between CTC status and CTCKIN, and response, PFS, and OS. RESULTS: 133/393 (34%) patients enrolled were CTCBL+. CTC1C status after one cycle and radiological tumor response were assessed after median (range) periods of 1.2 (0.5-3.2) and 2.9 (0.5-4.8) months, respectively. 57/201 (28%) were CTC1C+. Median [95% confidence interval] PFS and OS (months) were significantly reduced in CTCBL+ vs. CTCBL- patients (PFS 4.7 [3.7-6.1] vs. 7.8 [6.4-9.2]; OS 10.4 [7.9-15.0] vs. 27.2 [22.3-29.9]), and for CTC1C+ vs. CTC1C- patients (PFS 4.3 [3.6-6.0] vs. 8.5 [6.6-10.4]; OS 7.7 [6.4-13.9] vs. 30.6 [22.6-not available]). Unfavorable CTCKIN was significantly associated with progressive disease. Multivariate Cox regression analysis revealed prognostic factors for shorter PFS (CTCBL+, persistent CTCs after one cycle, 〉/= 3rd-line therapy, and triple-negative receptor status) and shorter OS (CTCBL+, persistent CTCs after one cycle, bone-and-visceral/local metastases, 〉/= 3rd-line therapy, and triple-negative receptor status). CONCLUSIONS: CTCBL, CTC1C, and CTCKIN are predictive of outcome in MBC. Serial CTC enumeration is useful in tailoring systemic treatment of MBC. TRIAL REGISTRATION: Not applicable.
    Type of Publication: Journal article published
    PubMed ID: 25015676
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