scholarly journals RELATIONSHIP OF LYMPHOCYTE SUBPOPULATIONS IN BREAST CANCER PATIENTS WITH TREATMENT RESULTS

2021 ◽  
Vol 20 (3) ◽  
pp. 25-33
Author(s):  
T. N. Zabotina ◽  
A. I. Chertkova ◽  
A. A. Borunova ◽  
E. N. Zakharova ◽  
E. K. Shoua ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Tissue ◽  
Molecular Subtype ◽  
Lymphocyte Subpopulations ◽  
Local Immunity ◽  
Results Of Treatment ◽  
Immune Biomarkers ◽  
High Level ◽  
Lymphocyte Populations

Introduction. Breast cancer (BC) is an immunogenic tumor. Immune cells infiltration of tumor tissue can affect the clinical course of the disease. The immunogenicity of breast cancer varies depending on the molecular subtype.The aim of this work was to study the main indicators of systemic and local immunity before patient’s treatment and to determine their relationship with the immediate neoadjuvant chemotherapy results.Materials and methods. Patients with stage II–III BC received standard neoadjuvant chemotherapy in accordance with the molecular subtypes. The percentage of the main effector and regulatory lymphocytes populations of systemic and local immunity was determined by flow cytometry.Results. A decrease in the level of effector CD8 and CD4 lymphocyte populations and an increase in the level suppressor populations in tumor tissue in comparison with peripheral blood indicate an immunosuppressive state of local immunity in BC patients. In tumor tissue, a high level of CD8+ PD-1+ and CD4+ PD-1+ cells were associated with a high level of regulatory CD4+ CD25highCD127–/low and CD8+ CD11b– CD28– lymphocytes. Differences were found in the significance of individual lymphocyte populations for the immediate results of treatment between patients with different subtypes of breast cancer.Conclusion. Determination of lymphocyte subpopulations correlating with the level of PD-1 cells, and the results of treatment in patients with different molecular BC subtypes, will help a clearer understanding of the antitumor immune response in this pathology, and will also serve as a basis for identifying immune biomarkers that can be used as additional predictive factors in various treatment options for BC patients. 

Shear Wave Elastography Combined with Molecular Subtype in Early Predicting Response to Neoadjuvant Chemotherapy for Breast Cancer: A Prospective Case-control Study

2021 ◽  
Author(s):  
Jia-Xin Huang ◽  
Shi-Yang Lin ◽  
Yan Ou ◽  
Cai-Gou Shi ◽  
Yuan Zhong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Case Control Study ◽  
Molecular Subtype ◽  
Shear Wave Elastography ◽  
Predictive Performance ◽  
Case Control ◽  
Pathological Response ◽  
Control Study ◽  
Prospective Case Control Study

Abstract Background: This study was designed to investigate the performance of quantitative shear wave elastography (SWE) and the accuracy of SWE with the molecular subtype for early prediction of pathological response of breast cancer to neoadjuvant chemotherapy (NAC).Methods: In this prospective case-control study, 102 patients were screened from September 2016 to August 2020. Characteristics of conventional ultrasonography (US), SWE and contrast-enhanced magnetic resonance imaging (CE-MRI), were recorded, and the changes were compared to the pre-NAC baseline data. The pathological response was classified according to the Miller Payne grading system. Multivariate logistic regression was used to develop a predictive model for the response to NAC. Results: Significant differences related to changes in SWE characteristics of breast lesions between between pathological response groups were observed earlier than size on the conventional US and MRI images. According to the multivariate predictive model, the best parameter for predicting the pathological response after the first cycle of NAC was the molecular subtype of the tumor [area under the curve (AUC) = 0.83] with low sensitivity (66.04%). Better predictive performance was achieved when △AE/B and the molecular subtype were applied in combination after the second cycle of NAC (AUC = 0.92) with a higher sensitivity (86.79%). The predictive performance of molecular subtype combined with △AE/B and △SWVmean after the third and fourth cycles of NAC were improved (AUC = 0.94).Conclusion: The SWE can be an early predictor of the pathological response to NAC for breast cancer. The combination of SWE and the molecular subtype may be a preferred method for the clinical evaluation of NAC to facilitate the personalization of treatment regimens for breast cancer.

scholarly journals Predictive and prognostic role of tumour-infiltrating lymphocytes in breast cancer patients with different molecular subtypes: a meta-analysis

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhao-hua Gao ◽  
Cun-xin Li ◽  
Ming Liu ◽  
Jia-yuan Jiang
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Predictive Value ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Meta Analysis ◽  
Breast Cancer Patients ◽  
Tumour Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

Abstract Background Whether tumour-infiltrating lymphocytes (TILs) play different roles in different molecular subtypes of breast cancer remains unknown. Additionally, their prognostic and predictive value in different molecular subtypes of breast cancer is still controversial. The aim of our meta-analysis was to assess the prognostic and predictive value of TILs in different molecular subtypes of breast cancer by summarizing all relevant studies performing multivariate analysis. Methods PubMed, Embase, EBSCO, ScienceDirect, the Cochrane Database and Web of Science were comprehensively searched (until March 2020). Hazard ratios (HRs), odds ratios (ORs) and their 95% confidence intervals (CIs) were used as effect measures to perform our meta-analysis. A random effect model was used. Stata software, version 15 (2017) (StataCorp, College Station, TX, USA) was used to perform the statistical analysis. Results Thirty-three studies including 18,170 eligible breast cancer patients were analysed. The meta-analysis showed that high TIL expression was significantly associated with increased pathological complete response (pCR) rates after neoadjuvant chemotherapy in patients with the HER2-enriched molecular subtype (OR = 1.137, 95% CI [1.061 ~ 1.218], p < 0.001) and triple-negative breast cancer (TNBC) subtype (OR = 1.120, 95% CI [1.061 ~ 1.182], p < 0.001). However, high TIL expression was not significantly associated with high pCR rates after neoadjuvant chemotherapy in patients with the luminal molecular subtype of breast cancer (OR = 1.154, 95% CI [0.789 ~ 1.690], p = 0.460). We carried out a meta-analysis on the HRs of overall survival (OS) and disease-free survival (DFS) to assess the prognostic value of TILs in breast cancer with different molecular subtypes more deeply. Our meta-analysis confirmed that high TILs were associated with significantly improved DFS in patients with the HER2-enriched molecular subtype [HR = 0.940, 95% CI (0.903 ~ 0.979), p = 0.003] and TNBC molecular subtype [HR = 0.907, 95% CI (0.862 ~ 0.954), p < 0.001]. However, high TILs were not associated with significantly better DFS in patients with the luminal molecular subtype of breast cancer [HR = 0.998, 95% CI (0.977 ~ 1.019), p = 0.840]. Furthermore, the results confirmed that high TILs were significantly related to better OS in patients with the HER2-enriched molecular subtype [HR = 0.910, 95% CI (0.866 ~ 0.957), p < 0.001] and TNBC molecular subtype [HR = 0.869, 95% CI (0.836 ~ 0.904), p < 0.001]. Conversely, the summarized results indicated that high TILs were significantly associated with poor OS in patients with the luminal molecular subtype of breast cancer [HR = 1.077, 95% CI (1.016 ~ 1.141), p = 0.012]. Conclusions Our meta-analysis confirms that high TILs are associated with favourable survival and predicts pCR in breast cancer patients with the TNBC and HER2-enriched molecular subtypes.

scholarly journals Mirna21 Expression in the Breast Cancer Tumor Tissue is Independent of Neoadjuvant Chemotherapy

2020 ◽  
Vol Volume 12 ◽  
pp. 141-151
Author(s):  
Alexandre Cesar Vieira Sales ◽  
Isaura Isabelle Fonseca Gomes da Silva ◽  
Matheus CB Leite ◽  
Leandro L Coutinho ◽  
Renata BAC Reis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Tissue ◽  
Cancer Tumor

scholarly journals PROGNOSIS OF NEOADJUVANT CHEMOTHERAPY EFFICACY WITH IMMUNOBIOLOGIC TUMOR MARKERS IN PATIENTS WITH TRIPLE NEGATIVE BREAST CANCER

2019 ◽  
pp. 46-54
Author(s):  
S. A. Lyalkin ◽  
N. O. Verevkina ◽  
L. A. Syvak
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Fold Increase ◽  
Predictive Role ◽  
High Level ◽  
Chemotherapy Efficacy ◽  
Cd4 Lymphocytes

Treatment of patients with triple negative breast cancer (TNBC) remains one of the most difficult problems in clinical oncology. Despite the negative prognosis for TNBC, there exists the group of patients with better response to the therapy and better prognosis, which proves the heterogenity of TNBC. The aim of the study was to evaluate the predictive role of tumor infiltrative lymphocytes (TIL) and their subpopulations (CD4+, CD8+ and FOXP3) in patients with TNBC. The predictive role of clinical, morphologic and immunohystochemical tumor features on neoadjuvant chemotherapy (NACT) efficacy was assessed in 52 TNBC patients. The risk of incomplete pathomorphologic response after NACT is related with 2 biomarkers: level of TIL and stromal CD4+ lymphocytes. The increase of TIL level decreases of the risk of incomplete pathomorphologic response (P = 0.01), ОR = 0.07 (95 % CІ 0.01–0.55) while standartization on CD4+ level. The high level of TIL at the time of diagnosis significantly decreases the risk of incomplete pathomorphologic response (OR = 0,2; P = 0,02). The group of patients with the ratio of stromal lymphocytes CD4low/CD8low had the eight-fold increase of the risk of incomplete pathomorphologic response comparing with the group with the ratio CD4high/CD8high (ОR = 8,0; Р = 0,03); the patient with the ratio stromal lymphocytes CD8low/ FOXP3low had the almost two-fold increase of the risk of incomplete pathomorphologic response comparing with the group with the ratio CD8high/FOXP3high (ОR = 2,1; Р = 0,03).

Prognostic significance of amplifications of stemness genes in primary luminal breast cancer depending on the response to neoadjuvant chemotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14655-e14655
Author(s):  
Polina Kazantseva ◽  
Elena Slonimskaya ◽  
Nicolay Litviakov ◽  
Matvey Tsyganov ◽  
Marina Ibragimova
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Median Survival ◽  
Tumor Tissue ◽  
Prognostic Significance ◽  
Complete Regression ◽  
Primary Tumors ◽  
Free Survival ◽  
Group 2 ◽  
Group 1

e14655 Background: Neoadjuvant chemotherapy (NAС) is one of the treatment options for breast cancer (BC). However, chemotherapy is known can cause intratumoral changes that increase the risk of metastasis. We have previously found that the appearance of new amplifications in the chromosomal regions harboring stemness genes (3q, 5p, 6p, 7q, 8q, 9p, 9q, 10p, 10q21.1, 13q, 16p, 18Chr, 19p) is associated with the development of hematogenous metastases in 100% of cases. In our study, we evaluated the prognostic significance of amplifications stemness genes in primary BC depending on the NAC response. Methods: The study included 104 patients with stage II-III luminal B (Her2Neu -) breast cancer. All patients received 4-8 courses of NAС followed by surgery and hormone therapy. The follow-up period was 4-10 years. Amplifications in primary tumor DNA were determined using Affymetrix high density microarrays. Metastasis-free survival was estimated using the Kaplan-Meier method. Results: Zero or only 1 amplification was identified in tumor tissue of 42 patients (41%) (group 1). Two or more amplifications were identified in tumor tissue of 60 patients (59%) (group 2). We evaluated metastasis-free survival separately in each group, depending on the NAС response. It was found that in group 1, the median survival time was 122 months in cases with partial or complete regression (PR + pCR, and 63 months in cases with stable disease or disease progression (S + P), p > 0.05. In group 2, the median survival of patients with PR + pCR was not reached, and it was 63 months in patients with S + P, p = 0.025. Conclusions: Achievement of partial or complete regression in breast cancer patients, whose primary tumors displayed 2 or more amplifications of stemness genes, was associated with the increased rates of metastasis-free survival and can be considered as a positive prognostic criterion. However, the response to NAC did not impact survival of patients with 0-1 amplification of stemness genes.

Clinicopathologic profile of breast cancer patients treated with neoadjuvant chemotherapy at HUCFF/UFRJ

Mastology ◽  
2021 ◽  
Author(s):  
Luís Claudio Belo Amendola ◽  
Maria de Fatima Dias Gaui ◽  
Ana Helena Pereira Correia Carneiro ◽  
Nathalie Henriques Silva Canedo
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Molecular Subtype ◽  
Pathologic Complete Response ◽  
Real Life ◽  
Public University ◽  
Public Institution ◽  
Breast Cancer Patients ◽  
Response To Chemotherapy

Introduction: The objective of this study is to describe the profile of patients from a public institution, submitted to neoadjuvant chemotherapy (NACT), comparing the verified pathological response with literature data. Methods: Observational retrospective cohort study on breast cancer patients diagnosed between September 2001 and October 2018 and treated with NACT at Hospital Universitário Clementino Fraga Filho (HUCFF/UFRJ), located in Rio de Janeiro, Brazil. The adopted neoadjuvant chemotherapy regimen was based on anthracycline and docetaxel. Results: A total of 133 patients were evaluated. The average age in this group was 54 years (28-86), 49 women (37%) were under 50 years old. The following distribution by molecular subtype was observed: overexpression or amplification of the human epidermal growth factor receptor 2 (HER2+) (13 women, 26.6%), Luminal (19 women, 38.8%), and Triple-negative (TN) (17 women, 34.6%). The HER2+ and TN subtypes had a higher incidence of cases between 40-49 years and 50-59 years. As for the initial staging, 34% were IIIA; 26%, IIB; and 19%, IIIB. Only one patient did not undergo surgery after NACT, 33 (24.8%) underwent conservative surgery, and 99 patients (74.4%) underwent mastectomy. Regarding the axillary approach, 41 (31%) underwent sentinel lymph node biopsy and 88 (66%) had an indication for lymphadenectomy. In the anatomopathological evaluation of the surgery, 12 (9.1%) patients obtained a pathologic complete response (pCR) and 113 (84.9%), partial or no response to chemotherapy. Conclusion: This research enabled the identification of clinicopathologic characteristics and outcome of patients who received neoadjuvant chemotherapy in a public university service. The predominance of advanced tumors was observed, stressing the need for public health policies for the screening of breast cancer as well as the guarantee of timely treatment for diagnosed cases. The data somewhat reflect the difficulty that the public sector encounters to carry out the most appropriate treatment. The authors expect that this article, by analyzing the profile and the adopted treatment in real-life cases and in a public university institution, can contribute to the improvement of breast cancer treatment in Brazil.

Validation of the Residual Cancer Burden Index as a prognostic tool in women with locally advanced breast cancer treated with neoadjuvant chemotherapy

2021 ◽  
pp. jclinpath-2021-207771
Author(s):  
Juliana Pierobon Gomes da Cunha ◽  
Rodrigo Goncalves ◽  
Fernando Silva ◽  
Fernando Nalesso Aguiar ◽  
Bruna Salani Mota ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Molecular Subtype ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Clinical Staging ◽  
Residual Cancer ◽  
Cancer Burden ◽  
Residual Cancer Burden

AimsTo correlate the ‘Residual Cancer Burden’ (RCB) index with overall survival (OS) and disease-free survival (DFS) in women undergoing neoadjuvant chemotherapy at the Cancer Institute of the State of São Paulo.MethodsWe analysed the medical records of patients with breast cancer who underwent neoadjuvant chemotherapy and breast surgery, from 2011 to December 2017. Variables analysed were age, clinical and pathological staging, molecular subtype, number of recurrences or metastases, number of deaths, value and class of the RCB index. We used the Kaplan-Meier and the log-rank statistics to evaluate the possible association between RCB and OS and DFS. A regression model was used to determine the independent association of the RCB with the outcomes controlling for confounding factors.Results347 patients were included in the analysis with a mean age of 49.39 years. Initial clinical staging was T3 in 57.9% of patients and 43.8% of patients had N1 axillary status. Survival analysis showed a statistically significant better prognosis for the RCB 0 (pCR) subgroup compared with RCB 1, 2 and 3 (log rank p=0.01). In a multivariate analysis, only the RCB classification showed a statistically significant correlation with DFS (RCB 1, HR 6.9, CI 1.9 to 25.4, p=0.004; RCB 2, HR 4.2, CI 1.6 to 10.8, p=0.03; and RCB 3, HR 7.6, CI 2.76 to 20.8, p=0.00).ConclusionWe demonstrated a positive and significant relationship between the RCB index and the risk of relapse and death.

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