Erratum to: The prognostic role of circulating tumor cells (CTCs) detected by RT-PCR in breast cancer: a meta-analysis of published literature

3036 Background: The presence of HER2 expressing (HER2+) circulating tumor cells (CTCs) occurs often in metastatic breast cancer (MBC) patients (pts). We have previously showed that the ratio among CTCs expressing high level of HER2 and the total number of HER2+ CTCs (circulating HER2 ratio, cHer2 ratio) has a prognostic role in MBC patients. Here we further investigate the role of the cHER2 ratio in the process of metastatic spread. Methods: Under IRB-approved study we prospectively analyzed blood samples of patients with MBC enrolled before starting a new line of therapy. Samples were collected from pts treated at Northwestern University (Chicago, IL) between 2016 and 2020. CTCs were enumerated through CellSearch (Menarini Silicon Biosystems, Bologna, Italy) and characterized for HER2 expression using the CellSearch CXC Kit. HER2+ CTCs were divided in 3 different categories (1+,2+,3+) leaning on fluorescence intensity. Pts with <5 CTCs (stage IV indolent) were excluded from the analysis. The cHER2 ratio, defined as the sum of 2+ CTCs and 3+ CTCs divided by the total number of HER2+ CTCs, was used to split the remaining pts in 2 different cohorts: cHER2 ratio high (> 0.75) (cHER2high) and cHER2 ratio low (≤0.75) (cHER2low). The frequency of each metastatic site (i.e. liver, lung, central nervous system, bone, lymph nodes, skin/soft tissue, serosa) and the total number of different sites involved (1-7, ≤2 and >2 sites) were compared among the two sub-populations and analyzed through Fisher exact test. Results: Out of 98 pts enrolled, 77 were classified as cHER2low and 21 as cHER2high. We observed a higher frequency of oligometastatic pts (≤2 sites involved) in the cHER2high cohort (16, 76%), compared to only 29 (37%) in the cHER2low (p<0.005). Moreover, the cHER2 ratio was associated with a tropism toward specific sites of disease spread with higher incidence of liver, lung and lymph nodes metastases in the cHER2low cohort (p<0.05). No other statistical associations were observed in respect of specific organ tropism. The frequency of involvement for each metastatic site among the two cohorts are reported in the table. Conclusions: Measuring CTCs enumeration and HER2 expression we identified two cohorts, cHER2high and cHER2low, associated with distinct patterns of metastatic spread. The cHER2low pts were correlated to multiple sites of metastatic involvement, with particular tropism toward liver, lung and lymph nodes. These results confirm the prognostic role of the cHER2 ratio, suggesting a peculiar biological meaning of the HER2+ 1+ CTCs.[Table: see text]

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The Prognostic Value of Circulating Tumor Cells in Primary Breast Cancer Prior to any Systematic Therapy: A Systematic Review

Current Stem Cell Research & Therapy ◽

10.2174/1574888x14666190306103759 ◽

2019 ◽

Vol 14 (6) ◽

pp. 519-529 ◽

Cited By ~ 4

Author(s):

Sepideh Mansouri ◽

Parisa Mokhtari-Hesari ◽

Fatemeh Naghavi-al-Hosseini ◽

Keivan Majidzadeh-A ◽

Leila Farahmand

Keyword(s):

Breast Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Primary Breast Cancer ◽

Meta Analysis ◽

Cochrane Library ◽

Breast Cancers ◽

Tumor Metastases ◽

Relapse Rates

Background:Numerous studies have defined the outstanding role of circulating tumor cells (CTC) in the management of cancer, particularly the ones in association with primary tumor metastases.Objective:The overall aim of the present study was to investigate whether CTCs may serve as a clinical prognostic marker for survival in primary breast cancer.Methods:Articles Published from June 2011 to July 2017 in PubMed, EMBase, and Cochrane library databases were thoroughly screened for selecting the ones meeting the inclusion criteria.Results:Studies applying CellSearch® method demonstrated the risk ratios (RR) of 2.51 (95% CI: 1.78- 3.54), 3.98 (95% CI: 2.28- 6.95), 5.59 (95% CI: 3.29- 9.51), and 3.38 (95% CI: 1.88- 6.06) for death rate and relapse rates of 2.48 (95% CI: 1.89 - 3.26), 3.62 (95% CI: 2.37 - 5.51), 4.45 (95% CI: 2.94 - 6.73), and 2.88 (95 % CI: 1.99 - 4.17) at four CTC positive cut points (≥ 1, ≥ 2, ≥ 3, and ≥ 5 CTCs/7.5 ml). Two studies applying the AdnaTest® also documented increased death (RR: 1.38, 95 % CI: 0.42- 4.49) and relapse rates (RR: 2.97, 95 % CI: 1.23 - 7.18)).Conclusion:Results of this meta-analysis allude CTCs as potent prognostic markers in primary breast cancers prior to any systemic therapy especially when it is studied via CellSearch® administration, considering that the more the CTCs, the greater the death and relapse rates.

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