Circulating Tumor Cells: A Novel Prognostic Factor for Newly Diagnosed Metastatic Breast Cancer

104

According to current treatment standards, patients with metastatic breast cancer at diagnosis receive palliative therapy. Local treatment of the breast is only recommended if the primary tumor is symptomatic. Recent studies suggest that surgical removal of the primary tumor has a favorable impact on the prognosis of patients with primary metastatic breast cancer. We performed a systematic review of the literature to weigh the evidence for and against breast surgery in this patient group. Ten retrospective studies were found in which the use of breast surgery in primary metastatic breast cancer and its impact on survival was examined. The hazard ratios of the studies were pooled to provide an estimate of the overall effect of surgery, and the results and conclusions of the studies were analyzed. A crude analysis, without adjustment for potential confounders, showed that surgical removal of the breast lesion in stage-IV disease was associated with a significantly higher overall survival rate in seven of the ten studies, and a trend toward a better survival in the three remaining studies. Surgery of the primary tumor appeared to be an independent factor for an improved survival in the multivariate analyses from the individual studies, with hazard ratios ranging from 0.47 to 0.71. The pooled hazard ratio for overall mortality was 0.65 (95% CI 0.59-0.72) in favor of the patients undergoing surgery. This systematic review of the literature suggests that surgery of the primary breast tumor in patients with stage-IV disease at initial presentation does have a positive impact on survival. In order to provide a definite answer on whether local tumor control in patients with primary metastatic disease improves survival, a randomized controlled trial comparing systemic therapy with and without breast surgery is needed.

Section: Total (95% Ci)mentioning

confidence: 73%

Impact of breast surgery on survival in patients with distant metastases at initial presentation: a systematic review of the literature

Ruiterkamp

Voogd

Bosscha

et al. 2009

104

“…Assessment of CTC using CellSearch has been cleared by the Food and Drug Administration as a prognostic indicator, in conjunction with other clinical methods, for patients with metastatic breast, prostate, and colorectal cancers. Studies in metastatic breast, colorectal, and prostate cancer showed that patients about to start new lines of chemotherapy could be divided into groups with favourable and unfavourable prognosis on the basis of the number of CTCs measured with the analytically valid CellSearch system(Veridex, Raritan, NJ, USA) [3,[5][6][7][8][9][10][11][12][13]20]. When studying the association between the number of CTCs and evolution of the disease, researchers generally use a single cutpoint to identify favorable and unfavorable response groups, such as 5 CTCs for MBC [3,4,14], three for metastatic colorectal cancer [11], and five for castration resistant prostate cancer [7].…”

Section: Discussionmentioning

confidence: 99%

“…Circulating tumor cells (CTCs) have been shown to be an independent prognostic factor in metastatic breast cancer (MBC) [3][4][5][6], in metastatic prostate cancer [7][8][9][10] and in metastatic colorectal cancer [11,12]. They represent a promising tool for therapeutic monitoring: an elevated number of CTCs measured at any time in the clinical course were associated with a high likelihood of a very short time to progression.…”

Section: Introductionmentioning

confidence: 99%

“…For example, in studies on MBC, a cutpoint of 5 CTCs has been generally adopted [3,4,13,14]. Dichotomization has some perceived advantages, such as simplicity, easy interpretation of the results, and functionality in clinical practice, but also some intrinsic problems, such as loss of information and statistical power, increased probability of false positive results, and impossibility of detecting nonlinear relationships between the predictor and the outcome [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Modeling the relationship between circulating tumour cells number and prognosis of metastatic breast cancer

Botteri

Sandri

Bagnardi

et al. 2009

Modeling the relationship between circulating tumour cells number and prognosis of metastatic breast cancer. Breast Cancer Research and Treatment, Springer Verlag, 2009, 122 (1), pp.211-217. <10.1007/s10549-009-0668-7>. EPIDEMIOLOGYModeling the relationship between circulating tumour cells number and prognosis of metastatic breast cancer Abstract Circulating tumor cell (CTC) count has been shown to be an independent predictor of progression in metastatic breast, prostate, and colorectal cancer. A cutpoint is generally used to identify favorable and unfavorable response groups. In this study, we propose an approach in which the number of CTCs is analyzed as a continuous predictor, to detect the shape of the relationship between CTCs and prognosis of metastatic breast cancer. We evaluated the association of baseline CTC with progression-free survival (PFS) and overall survival (OS) in a series of 80 patients treated for advanced breast cancer at the European Institute of Oncology, Milan. The association between CTCs and prognosis was analyzed with standard categorical survival analysis and spline regression models. At baseline, median age was 55 years; 33 patients were newly diagnosed with metastatic breast cancer (41%), while 28 (35%) and 19 (24%) were pretreated with one and two previous chemotherapy lines, respectively. After a median follow-up of 28 months, 76 disease progressions and 44 deaths were observed. Kaplan-Meier curves showed a clear association between CTCs and PFS (P-value 0.03) and OS (Pvalue \ 0.01). Patients with no CTC at baseline had a significantly better prognosis. When analyzing the CTCs as a continuous variable, we found an increase in risk with increasing number of CTCs, for both PFS and OS. The increase rate lessened after approximately 5 CTCs. CTCs represent a robust prognostic factor in the metastatic breast cancer setting. A nonlinear increase in risk of both progression and death with increasing number of CTCs was observed, with a lessening increase after approximately 5 CTCs. If distinct prognostic groups are to be identified, women with no CTC could plausibly represent a distinct favorable one.

“…In recent years, several assays to detect CTCs have been introduced [3]. CTCs measured with the FDA-approved CellSearch technique (Veridex™, Raritan, NJ) have prognostic value in metastatic breast cancer [4,5] and changes in CTC counts during systemic therapy can serve as early marker for response [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Detection of circulating tumor cells in breast cancer may improve through enrichment with anti-CD146

Mostert

Kraan

Vries

et al. 2010

PurposeMost assays to detect circulating tumor cells (CTCs) rely on EpCAM expression on tumor cells.Recently, our group reported that in contrast to other molecular breast cancer subtypes, "normallike" cell lines lack EpCAM expression and are thus missed when CTCs are captured with EpCAM-based technology [1]. Here, the use of CD146 is introduced to detect EpCAM-negative CTCs, thereby improving CTC detection. Methods CD146and EpCAM expression were assessed in our panel of 41 breast cancer cell lines. Cells from 14 cell lines, 9 of which normal-like, were spiked into healthy donor blood. Using CellSearch™ technology, 7.5 mL whole blood was enriched for CTCs by adding ferrofluids loaded with antibodies against EpCAM and/or CD146 followed by staining for Cytokeratin and DAPI. Hematopoietic cells and circulating endothelial cells (CECs) were counterstained with CD45 and CD34, respectively. A similar approach was applied for blood samples of 20 advanced breast cancer patients. ResultsEight of 9 normal-like breast cancer cell lines lacked EpCAM expression but did express CD146.Five of these 8 could be adequately recovered by anti-CD146 ferrofluids. Of 20 advanced breast cancer patients whose CTCs were enumerated with anti-EpCAM and anti-CD146 ferrofluids, 9 had CD146+ CTCs. ConclusionsCells from breast cancer cell lines that lack EpCAM expression frequently express CD146 and can be recovered by anti-CD146 ferrofluids. CD146+ CTCs are present in the peripheral blood of breast cancer patients with advanced disease. Combined use of anti-CD146 and anti-EpCAM is likely to improve CTC detection in breast cancer patients.3