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Circulating tumour cell enumeration does not correlate with Miller-Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy.

ABSTRACT: PURPOSE:The association between pathological complete response (pCR) in patients receiving neoadjuvant chemotherapy (NAC) for breast cancer and Circulating Tumour Cells (CTCs) is not clear. The aim of this study was to assess whether CTC enumeration could be used to predict pathological response to NAC in breast cancer as measured by the Miller-Payne grading system. METHODS:Twenty-six patients were recruited, and blood samples were taken pre- and post-NAC. CTCs were isolated using the ScreenCell device and stained using a modified Giemsa stain. CTCs were enumerated by 2 pathologists and classified as single CTCs, doublets, clusters/microemboli and correlated with the pathological response as measured by the Miller-Payne grading system. ?2 or ANOVA was performed in SPSS 24.0 statistics software for associations. RESULTS:89% of patients had invasive ductal carcinoma (IDC) and 11% invasive lobular carcinoma (ILC). At baseline 85% of patients had CTCs present, median 7 (0-161) CTCs per 3 ml of whole blood. Post-chemotherapy, 58% had an increase in CTCs. This did not correlate with the Miller-Payne grade of response. No significant association was identified between the number of CTCs and clinical characteristics; however, we did observe a correlation between pre-treatment CTC counts and body mass index, p?

SUBMITTER: O'Toole SA

PROVIDER: S-EPMC7220879 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Circulating tumour cell enumeration does not correlate with Miller-Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy.

O'Toole Sharon A SA Spillane Cathy C Huang Yanmei Y Fitzgerald Marie C MC Ffrench Brendan B Mohamed Bashir B Ward Mark M Gallagher Michael M Kelly Tanya T O'Brien Cathal C Ruttle Carmel C Bogdanska Anna A Martin Cara C Mullen Dorinda D Connolly Elizabeth E McGarrigle Sarah A SA Kennedy John J O'Leary John J JJ

Breast cancer research and treatment 20200506 3

<h4>Purpose</h4>The association between pathological complete response (pCR) in patients receiving neoadjuvant chemotherapy (NAC) for breast cancer and Circulating Tumour Cells (CTCs) is not clear. The aim of this study was to assess whether CTC enumeration could be used to predict pathological response to NAC in breast cancer as measured by the Miller-Payne grading system.<h4>Methods</h4>Twenty-six patients were recruited, and blood samples were taken pre- and post-NAC. CTCs were isolated using ...[more]

PMID: 32378053

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Project description:The aim of this study was to compare the gene expression profile changes breast tumors after the treatment with Anthracyclines and Taxanes. To this end, an oligonucleotide microarray was performed (Affymetrix’s HG-U133 Plus 2.0 array). This gene expression study was carried out on the biopsied tumor samples previous being treated with chemotherapy, and subsequently compared with themselves once treatment schedule ended. The post-chemotherapy biopsy was obtained from the surgical piece. The goal of this study was the finding of several genes related to apoptosis, proliferation, differentiation, survival and transformation-related genes and correlating their differences in expression with the degree of response to chemotherapy, determined by the Miller and Payne histological grading system. After informed consent, patients with a histologically confirmed diagnosis of breast cancer and scheduled chemotherapy treatment based on Anthracyclines and Taxanes (Treatment A: Epirubicin 90 mg/m2-Cyclophosphamide 600 mg/m2, 3 cycles bi-weekly and Paclitaxel 150 mg/m2-Gemcitabine 2500 mg/m2, 6 cycles bi-weekly ± weekly Herceptin 4 mg/Kg during the first week, 2 mg/Kg for the remaining 11 cycles; Treatment B: Doxorubicin 60 mg/m2-Pemetrexed 500 mg/m2, 4 cycles tri-weekly and Docetaxel 100 mg/m2, 4 cycles tri-weekly; Treatment C: Doxorubicin 60 mg/m2-Cyclophosphamide 600 mg/m2, 4 cycles tri-weekly and Docetaxel 100 mg/m2, 4 cycles tri-weekly ) were recruited for this study. Pre-chemotherapy and post-chemotherapy biopsies were examined by a pathologist who determined the Miller & Payne grade for each patient. Matching pairs of pre-chemotherapy and post-chemotherpy samples were divided into 3 groups according to Miller & Payne grade: group of bad response (Miller & Payne grades 1 and 2), group of mid response (Miller & Payne grade 3) and group of good response (Miller & Payne grades 4 and 5). Gene expression analysis was performed in paired samples as follows: mid response group post-chemotherapy biopsy vs pre-chemotherapy biopsy (Mid final vs initial). For this assay were necessary 20 samples being chosen according to histopathologic criteria (Miller & Payne grade 3). Other comparisons in which this group of samples was involved include: Initial Good vs Mid, Initial Bad vs Mid, Final Bad vs Mid and Final Good vs Mid. This gene expression profiling was carried out making use of Affymetrix’s GeneChip technology, with the Affymetrix’s HG-U133 Plus 2.0 array from this provider. All the protocols and apparatus were recommended by Affymetrix. Total RNA from frozen mammary tumors was directly extracted by a RNeasy Mini kit and homogenized by QIAshredder columns under manufacturer’s instructions. The quality and quantity of the obtained RNA, was checked out through agarose electrophoresis and later spectrophotometry at 260/280 nm. Biotinylated cRNA was synthesized following the IVT labeling kit from Affymetrix and purified by the GeneChip Sample Cleanup Module from Affymetrix. Once again, the quality and quantity of the obtained cRNA, was checked out through agarose electrophoresis and posterior spectrophotometry at 260/280 nm. After hybridization, slides were washed and scanned following the manufacturer’s standard protocol. Intensity values were normalized by Robust Multichip Average method and subsequently these were filtered for remove the control sequences and those with a hybridization signal near to background. The spike controls were: BioB, BioC, BioD and Cre; because BioB was the less presented in the samples, it was used to estimate the sensitivity of the experiment. The housekeeping control was GAPDH. After non-supervised PCA analysis and clustering, gene expression statistical significances were identified by two regression models taking into account the pathologic response to chemotherapy and if the sample was obtained before or after chemotherapy treatment. Supervised PCA analysis and clustering were performed with processed data. Partek Genomics Suite v7.3.1 (Partek) software was employed for the statistic analysis and clustering.

Project description:The aim of this study was to compare the gene expression profile changes breast tumors after the treatment with Anthracyclines and Taxanes. To this end, an oligonucleotide microarray was performed (AffymetrixM-bM-^@M-^Ys HG-U133 Plus 2.0 array). This gene expression study was carried out on the biopsied tumor samples previous being treated with chemotherapy, and subsequently compared with themselves once treatment schedule ended. The post-chemotherapy biopsy was obtained from the surgical piece. The goal of this study was the finding of several genes related to apoptosis, proliferation, differentiation, survival and transformation-related genes and correlating their differences in expression with the degree of response to chemotherapy, determined by the Miller and Payne histological grading system. After informed consent, patients with a histologically confirmed diagnosis of breast cancer and scheduled chemotherapy treatment based on Anthracyclines and Taxanes (Treatment A: Epirubicin 90 mg/m2-Cyclophosphamide 600 mg/m2, 3 cycles bi-weekly and Paclitaxel 150 mg/m2-Gemcitabine 2500 mg/m2, 6 cycles bi-weekly M-BM-1 weekly Herceptin 4 mg/Kg during the first week, 2 mg/Kg for the remaining 11 cycles; Treatment B: Doxorubicin 60 mg/m2-Pemetrexed 500 mg/m2, 4 cycles tri-weekly and Docetaxel 100 mg/m2, 4 cycles tri-weekly; Treatment C: Doxorubicin 60 mg/m2-Cyclophosphamide 600 mg/m2, 4 cycles tri-weekly and Docetaxel 100 mg/m2, 4 cycles tri-weekly ) were recruited for this study. Pre-chemotherapy and post-chemotherapy biopsies were examined by a pathologist who determined the Miller & Payne grade for each patient. Matching pairs of pre-chemotherapy and post-chemotherpy samples were divided into 3 groups according to Miller & Payne grade: group of bad response (Miller & Payne grades 1 and 2), group of mid response (Miller & Payne grade 3) and group of good response (Miller & Payne grades 4 and 5). Gene expression analysis was performed in paired samples as follows: mid response group post-chemotherapy biopsy vs pre-chemotherapy biopsy (Mid final vs initial). For this assay were necessary 20 samples being chosen according to histopathologic criteria (Miller & Payne grade 3). Other comparisons in which this group of samples was involved include: Initial Good vs Mid, Initial Bad vs Mid, Final Bad vs Mid and Final Good vs Mid. This gene expression profiling was carried out making use of AffymetrixM-bM-^@M-^Ys GeneChip technology, with the AffymetrixM-bM-^@M-^Ys HG-U133 Plus 2.0 array from this provider. All the protocols and apparatus were recommended by Affymetrix. Total RNA from frozen mammary tumors was directly extracted by a RNeasy Mini kit and homogenized by QIAshredder columns under manufacturerM-bM-^@M-^Ys instructions. The quality and quantity of the obtained RNA, was checked out through agarose electrophoresis and later spectrophotometry at 260/280 nm. Biotinylated cRNA was synthesized following the IVT labeling kit from Affymetrix and purified by the GeneChip Sample Cleanup Module from Affymetrix. Once again, the quality and quantity of the obtained cRNA, was checked out through agarose electrophoresis and posterior spectrophotometry at 260/280 nm. After hybridization, slides were washed and scanned following the manufacturerM-bM-^@M-^Ys standard protocol. Intensity values were normalized by Robust Multichip Average method and subsequently these were filtered for remove the control sequences and those with a hybridization signal near to background. The spike controls were: BioB, BioC, BioD and Cre; because BioB was the less presented in the samples, it was used to estimate the sensitivity of the experiment. The housekeeping control was GAPDH. After non-supervised PCA analysis and clustering, gene expression statistical significances were identified by two regression models taking into account the pathologic response to chemotherapy and if the sample was obtained before or after chemotherapy treatment. Supervised PCA analysis and clustering were performed with processed data. Partek Genomics Suite v7.3.1 (Partek) software was employed for the statistic analysis and clustering.

Project description:IntroductionHR+/HER2- breast cancer (BC) has a much lower pathological complete response (pCR) rate to neoadjuvant chemotherapy (NAC). Therefore, to better stratify the relapse risk for HR+/HER2- non-pCR populations, it is essential to accurate identification new prognostic markers.Materials and methodsThe study retrospectively analyzed 105 stage II-III patients who were diagnosed with HR+/HER2- BC and received NAC followed by breast and axilla surgery between 2013 and 2019 in Sun Yat-Sen University Cancer Center. The Miller-Payne (MP) grading system was used to evaluate pathological responses to NAC. The 70-gene signature was used to classify the prognosis signatures.ResultsAmong the 105 patients, the study demonstrated that larger tumor size and lower progesterone receptor level at baseline and larger tumor size postoperative were statistically significantly associated with worse disease-free survival (DFS) (p = 0.004, p = 0.021, and p = 0.001, respectively). Among 54 patients who underwent the 70-gene assays, 26 (48.1%) had a low-risk signature; 28 (51.9%) patients had a high-risk signature. Patients with poor response (MP grades 1-2) were more likely to with a high-risk 70-gene signature than those with good response (MP grades 4-5). The final analysis showed that DFS was longer in the low-risk group than in the high-risk group [52.4 vs. 36.1 months of the median DFS, hazard ratio (HR) for recurrence, 0.29; 95% confidence interval (CI), 0.10-0.80; p = 0.018]. DFS was longer in the good response (MP grades 3-4) group than in the poor response (MP grades 1-2) group (94.7% vs. 60% of the patients free from recurrence; HR, 0.16; 95% CI, 0.05-0.47; p = 0.037). When stratified by MP grades combined with the 70-gene signature, subgroup analyses showed the good-response low-risk group with the best DFS, whereas the poor-response high-risk group showed the worst DFS (p = 0.048). Due to the short median follow-up time of 34.5 months (5.9-75.1 months), MP grades and the 70-gene signature did not show significant prognostic value for overall survival.ConclusionThe study showed that analysis of MP grades combined with the 70-gene signature with residual NAC-resistant breast samples has a significant correlation with DFS.

Project description:BackgroundGuidelines recommend neoadjuvant chemotherapy (NAC) for the treatment of nonmetastatic muscle-invasive bladder cancer (MIBC). NAC is, however, underutilized in practice because of its associated limited overall survival (OS) benefit and significant treatment-related toxicity. We hypothesized that the absence of circulating tumour cells (CTCs) identifies MIBC patients with such a favourable prognosis that NAC may be withheld.Patients and methodsThe CirGuidance study was an open-label, multicentre trial that included patients with clinical stage T2-T4aN0-N1M0 MIBC, scheduled for radical cystectomy. CTC-negative patients (no CTCs detectable using the CELLSEARCH system) underwent radical surgery without NAC; CTC-positive patients (≥1 detectable CTCs) were advised to receive NAC, followed by radical surgery. The primary endpoint was the 2-year OS in the CTC-negative group with a prespecified criterion for trial success of ≥75% (95% confidence interval (CI) ±5%).ResultsA total of 273 patients were enrolled. Median age was 69 years; median follow-up was 36 months. The primary endpoint of 2-year OS in the CTC-negative group was 69.5% (N = 203; 95% CI 62.6%-75.5%). Two-year OS was 58.2% in the CTC-positive group (N = 70; 95% CI 45.5%-68.9%). CTC-positive patients had a higher rate of cancer-related mortality [hazard ratio (HR) 1.61, 95% CI 1.05-2.45, P = 0.03] and disease relapse (HR 1.87, 95% CI 1.28-2.73, P = 0.001) than CTC-negative patients. Explorative analyses suggested that CTC-positive patients who had received NAC (n = 22) survived longer than CTC-positive patients who had not (n = 48).ConclusionThe absence of CTCs in MIBC patients was associated with improved cancer-related mortality and a lower risk of disease relapse after cystectomy; however, their absence alone does not justify to withhold NAC. Exploratory analyses suggested that CTC-positive MIBC patients might derive more benefit from NAC.Trial registrationNetherlands Trial Register NL3954; https://www.trialregister.nl/trial/3954.

Dataset Information

Circulating tumour cell enumeration does not correlate with Miller-Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy.

Publications

Circulating tumour cell enumeration does not correlate with Miller-Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy.

Similar Datasets

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