Prognostic importance of peripheral blood parameters in  HER-2 positive metastatic breast cancer treated by pertuzumab, trastuzumab and docetaxel

Objective: There are some studies about the significance of the peripheral blood parameters in breast cancer. However, there is very few studies about prognostic importance of peripheral blood parameters in human epidermal growth factor-2 receptor (Her-2) positive breast cancer. We aimed to evaluate whether prognostic significance of peripheral blood parameters in patients Her-2 positive metastatic breast cancer with treated Pertuzumab, Trastuzumab, Docetaxel (PTD) Material and Methods: We included 56 patients with Her-2 positive metastatic breast cancer patients who were treated with PTD. We recorded patients' clinical,demographic features and we obtained peripheral blood parameters such as neutrophil-lymphocyte ratio (NLR), red blood cell distribution (RDW), mean platelet volume (MPV), lymphocyte, neutrophil after the sixth cycle of the treatment and before the treatment. We separated the patients into two groups depending on the progression status. Progression-free survival was analyzed by Kaplan-Meier statistical analysis. Results: Patients mean age was 50.7. Progression was detected in 34 patients. When we explored and compared hemogram parameters in the groups before the treatment, there wasn’t statistically any significant difference between these parameters such as neutrophil, lymphocyte, neutrophil to lymphocyte ratio, mean platelet volume, red blood cell width. In the progressive group;,while pretreatment NLR was 3.83, it was detected 2.72 after six cycle treatment and difference was meaningful ( p: 0.043). The pretreamtent MPV was 8.63, and It was 8.15 after six cycle treatment, and difference between these counts was statistically important (p: 0.006). PFS was 18.0 months in the study group. Conclusion: Peripheral blood parameters were not statistically significant in both group comparisons. In the progression group, the difference between NLR and MPV count was statistically significant after the sixth cycle of the treatment and before the treatment.

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Circulating Tumor Cells in HER-2 Positive Metastatic Breast Cancer Patients Treated with Trastuzumab and Chemotherapy

The International Journal of Biological Markers ◽

10.1177/172460080902400101 ◽

2009 ◽

Vol 24 (1) ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Raquel A. Nunes ◽

Xiaochun Li ◽

Soonmo Peter Kang ◽

Harold Burstein ◽

Lisa Roberts ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Treatment Response ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Peripheral Blood ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Her 2

The detection of circulating tumor cells (CTCs) in peripheral blood may have important prognostic and predictive implications in breast cancer treatment. A limitation in this field has been the lack of a validated method of accurately measuring CTCs. While sensitivity has improved using RT-PCR, specificity remains a major challenge. The goal of this paper is to present a sensitive and specific methodology of detecting CTCs in women with HER-2-positive metastatic breast cancer, and to examine its role as a marker that tracks disease response during treatment with trastuzumab-containing regimens. The study included patients with HER-2-positive metastatic breast cancer enrolled on two different clinical protocols using a trastuzumab-containing regimen. Serial CTCs were measured at planned time points and clinical correlations were made. Immunomagnetic selection of circulating epithelial cells was used to address the specificity of tumor cell detection using cytokeratin 19 (CK19). In addition, the extracellular domain of the HER-2 protein (HER-2/ECD) was measured to determine if CTCs detected by CK19 accurately reflect tumor burden. The presence of CTCs at first restaging was associated with disease progression. We observed an association between CK19 and HER-2/ECD. The association of HER-2/ECD with clinical response followed a similar pattern to that seen with CK19. Finally, the absence of HER-2/ECD at best overall response and a change of HER-2/ECD from positive at baseline to negative at best overall response was associated with favorable treatment response. Our study supports the prognostic and predictive role of the detection of CTCs in treatment of HER-2-positive metastatic breast cancer patients. The association between CK19 and markers of disease burden is in line with the concept that CTCs may be a reliable measure of tumor cells in the peripheral blood of patients with metastatic breast cancer. The association of CTCs at first restaging with treatment failure indicates that CTCs may have a role as surrogate markers to monitor treatment response.

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Epithelial-Mesenchymal-Transition-Like Circulating Tumor Cell-Associated White Blood Cell Clusters as a Prognostic Biomarker in HR-Positive/HER2-Negative Metastatic Breast Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.602222 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiuwen Guan ◽

Chunxiao Li ◽

Yiqun Li ◽

Jiani Wang ◽

Zongbi Yi ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Blood Cell ◽

White Blood Cell ◽

Peripheral Blood ◽

Epithelial Mesenchymal Transition ◽

Metastatic Breast ◽

Blood Samples ◽

Mesenchymal Transition ◽

Cell Clusters

BackgroundAlthough positive Circulating tumor cells (CTCs) status has been validated as a prognostic marker in breast cancer, the interaction between immune cells and CTCs during the progress of Epithelial-mesenchymal-transition (EMT), and the clinical implications of CTC-associated white blood cell clusters (CTC-WBC clusters) for metastatic breast cancer are largely uncharacterized.MethodsWe optimized a filter-based method combined with an RNA in situ hybridization technique according to the epithelial- and mesenchymal-markers to analyze EMT in CTC-WBC clusters. Serial peripheral blood samples from 135 patients with Hormone receptor (HR)-positive/HER2-negative metastatic breast cancer receiving first-line chemotherapy with docetaxel plus capecitabine were prospectively collected until disease progression from Nov 2013 to March 2019. Follow-up data collection was conducted until July 2020.ResultsA total of 452 blood samples at all time-points were collected and analyzed. Median age of the cohort was 51.0 years (range, 27 to 73 years), and most of them (76.3%) had visceral metastases. Median progression-free survival (PFS) was 10.6 months (95% CI, 8.8 to 12.3 months). The presence of EMT-like CTC-WBC clusters was more frequently evident among patients with simultaneous bone and lymph node metastases (87.5% vs 36.2%, P=0.006), whereas no associations were observed between CTC-WBC clusters and other clinicopathologic characteristics before chemotherapy. The patients with EMT-like CTC-WBC clusters tended to show a significantly increased number of total CTC count (median,19.0 vs 5.0, P<0.001). The patients with at least one detectable EMT-like CTC-WBC cluster at baseline were characterized by significantly worse PFS, when compared to the patients with no EMT-like CTC-WBC clusters detected (7.0 vs 10.7 months, P=0.023), and those with five or more epithelial-based CTCs detected per 5mL of peripheral blood (7.0 vs 12.7 months, P=0.014). However, the total CTC-WBC clusters were not correlated with patients’ survival in the cohort (8.4 vs 10.6 months, P=0.561).ConclusionsOur data provide evidence that the emergence of CTC-WBC clusters underwent EMT before treatment is associated with significantly poorer PFS in HR-positive/HER2-negative metastatic breast cancer patients receiving docetaxel plus capecitabine, which may be used as a parameter to predict the clinical outcomes and a potential target for individualized therapy.

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