scholarly journals Stromal Tumor Infiltrating Lymphocytes (sTILs) as a putative prognostic marker to identify a responsive subset of TNBC in an Indian Breast Cancer Cohort.

2020 ◽  
Author(s):  
Pooja Vaid ◽  
Anirudha Puntambekar ◽  
Rituja Banale ◽  
Ruhi Reddy ◽  
Rohini Unde ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Response To Therapy ◽  
Stromal Tumor ◽  
Breast Cancer Patients ◽  
Infiltrating Lymphocytes ◽  
Disease Free

Objectives Prognostic significance of stromal tumor infiltrating lymphocytes; sTILs is evaluated to identify a responsive subset of TNBC in an Indian cohort of breast cancer patients. Methods A retrospective cohort of breast cancer patients from a single onco-surgeon breast cancer clinic treated with uniform treatment strategy across is evaluated for sTILs. FFPE tissue of primary tumor of invasive breast carcinoma are collected with ethical approvals. Tumor sections blinded for subtypes are stained with H&E and scored for sTILs by a pathologist following Immuno-Oncology TILs working groups scoring guidelines. Results Analysis of 144 primary breast tumors for sTILs scores re-enforces significantly higher infiltration in TNBC tumors than HER2+ve and ER+ve tumors. Higher sTILs scores co-relate with gradually incremental pathological response to therapy specifically in TNBC subset and with better disease-free survival outcomes. Within TNBC, older and post-menopausal patients harbor higher scores of sTILs. Conclusion Despite a small cohort of breast cancer patients, TNBC subtype reflected significantly higher scores of sTILs with better response to therapy and disease-free outcomes as compared to other breast cancer subtypes. A larger number of breast cancer patients from an Indian cohort will strengthen the findings to establish sTILs as a marker to identify a responsive subset of TNBC.

Incidence and Prognostic Significance of Complete Axillary Downstaging After Primary Chemotherapy in Breast Cancer Patients With T1 to T3 Tumors and Cytologically Proven Axillary Metastatic Lymph Nodes

2002 ◽  
Vol 20 (5) ◽  
pp. 1304-1310 ◽  
Author(s):  
Roman Rouzier ◽  
Jean-Marc Extra ◽  
Jerzy Klijanienko ◽  
Marie-Christine Falcou ◽  
Bernard Asselain ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Primary Chemotherapy ◽  
Axillary Lymph ◽  
Breast Cancer Patients ◽  
Distant Disease ◽  
Free Survival ◽  
Disease Free

PURPOSE: To determine the incidence and prognostic significance of eradication of cytologically proven axillary lymph node metastases in breast cancer patients treated with primary chemotherapy. PATIENTS AND METHODS: Between January 1985 and December 1994, 152 breast cancer patients with invasive T1 to T3 tumors and axillary metastases cytologically proven by fine-needle sampling underwent primary chemotherapy followed by lumpectomy or mastectomy, level I and II axillary lymph node dissection, and irradiation. We studied pathologic complete responses (pCRs) of axillary nodes and breast tumors, as well as predictors of distant metastases. RESULTS: Thirty-five patients (23%) had axillary pCRs, and 20 patients (13.2%) had pCRs of primary breast tumors. Scarff-Bloom-Richardson grade 3 tumors (P = .04) and a clinical response to chemotherapy ≥ 50% (P = .003) were associated with negative axillary status at dissection. An initial tumor size ≤ 3 cm (63 patients) was associated with pCR of the primary tumor (P = .02) but not with complete histologic clearance of axillary lymph nodes. The median length of follow-up was 75 months. In the univariate analysis, age greater than 40 years (P = .003), absence of residual nodal disease (P = .01), and pCR of the tumor (P = .05) were associated with better distant disease-free survival. Five-year distant disease-free survival rates were 73.5% ± 14.9% among patients with no involved nodes at the time of surgery and 48.7% ± 9.2% among patients with residual nodal disease. In the multivariate Cox regression analysis, parameters associated with poor distant disease-free survival were age ≤ 40 years (P = .002), persistence of nodal involvement (P = .03), and S-phase fraction greater than 4% (P = .02). CONCLUSION: Our results suggest that axillary status is a better prognostic factor than response of the primary tumor to primary chemotherapy.

scholarly journals The tumor-infiltrating effector regulatory T cell:CD8+ lymphocyte ratio in invasive breast cancer

2019 ◽  
Author(s):  
Morihito Okada ◽  
Noriko Goda ◽  
Shinsuke Sasada ◽  
Hideo Shigematsu ◽  
Norio Masumoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Invasive Breast Cancer ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Compete Response ◽  
Infiltrating Lymphocytes

Abstract Background Tumor-infiltrating lymphocytes (TILs) in breast cancer comprise immunostimulating and immunosuppressive components. Although FOXP3+ TILs are prototypical immunosuppressive TILs, only effector regulatory T cells (eTreg), a subset of immunosuppressive FOXP3+ TILs, are undetectable on immunohistochemical staining. This study aimed to evaluate the immunosuppressive potential of eTregs and the role of prototypical immunostimulatory CD8+ TILs in invasive breast cancer. Methods Fresh TILs extracted from 84 invasive breast cancer patients were analyzed via flow cytometry. We evaluated eTregs (CD4+FOXP3highCD45RA−), other FOXP3+ Treg subsets (naïve and non-Tregs), and total CD8+CD4- TILs. Clinicopathological factors, including histopathological characteristics, were also assessed. Results The median eTreg proportion of the total CD4+TILs was 18.7% (interquartile range [IQR], 16.4–25.5%); CD8+TILs, 124% (IQR, 87.5–140%). The proportion of eTregs to total FOXP3+ TILs varied (median, 65.6%; range, 10.1–93.2%). In an immunosuppression assay, only eTregs displayed potent immunosuppression; however, other Treg subsets did not. Among 39 patients who received neoadjuvant chemotherapy, eTreg subsets and pathological compete response (pCR) did not differ significantly, while pCR rates were significantly higher among individuals with a high than those with a low CD8+/eTreg ratio (90.2% vs 33.3%; P<0.05). Among all patients, a high CD8+/eTreg ratio tended to be associated with better disease-free survival rather than a low CD8+/eTreg ratio (P=0.09). Conclusions The CD8+/eTreg ratio is simple, optimal indicator of cancer immunity, and a high CD8+/eTreg ratio enhances the prognosis and treatment response in invasive breast cancer patients. However, further studies are required to validate the present findings.

scholarly journals Predictive Value of Tumor Infiltrating Lymphocytes in Neoadjuvant Chemotherapy Treated Breast Cancer: A Meta-Analysis of 8052 Patients

2020 ◽  
Author(s):  
Shiqi Li ◽  
Ying Zhang ◽  
Shujun Wang ◽  
Rui Yang
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Tumor Infiltrating Lymphocytes ◽  
Breast Cancer Patients ◽  
Infiltrating Lymphocytes ◽  
Positive Breast Cancer

Abstract Background: We conducted a meta-analysis to determine the prognostic value of Tumor infiltrating lymphocytes (TILs) for patients with breast cancer on Neoadjuvant Chemotherapy, to explore the prognostic value of different TILs threshold in terms of pathological complete response (PCR).Methods: A systematic search of PubMed, EMBASE and Web of Science electronic databases was conducted to identify eligible articles published before September 2020. Data from studies were analyzed by using Review Manager 5.3 and Stata 15.0Results: A total of 22 published studies (including 8 052 patients) were eligible. Patients with high TILs level showed a higher rate of PCR to treatment (OR=3.182, 95 %CI, 2.549-3.973) compared to breast cancer patients with low TILs level. Although the association of TILs with response to neoadjuvant chemotherapy was similar across most breast cancer subtypes, there were a few differences ER negative or ER positive breast cancer. In studies (Type of breast cancer not clearly classified in the literature) where the cut-off value for TILs was ≥10 %, higher levels of total TILs predicted a higher PCR rate of Neoadjuvant Chemotherapy. However, for HER2-positive breast cancer patients, when a cut-off valve of TILs ≥ 30 % was used, the OR was 2.631 (95 % CI, 1.739-3.982, P = 0.000). TILs also were related to better DFS (HR=0.95, 95 %CI, 0.92-0.98, P=0.000) and overall survival (OS) (HR=0.90, 95 %CI, 0.85-0.95, P<0.0001) after Neoadjuvant Chemotherapy.Conclusions: TILs can be used as predictors of patients with breast cancer on Neoadjuvant Chemotherapy. TILs threshold with the greatest prognostic significance of PCR is as yet unknown, but a TILs threshold of at least 30 % is associated with the most powerful outcome prognostication of PCR.

Neutrophil-lymphocyte index as prognostic factor for overall survival and disease-free survival in breast cancer patients

2020 ◽  
Vol 33 (4) ◽  
pp. 137-144
Author(s):  
Guillermo Peralta-Castillo ◽  
Antonio Maffuz-Aziz ◽  
Mariana Sierra-Murguía ◽  
Sergio Rodriguez-Cuevas
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Disease Free

scholarly journals Use of Germline Genetic Variability for Prediction of Chemoresistance and Prognosis of Breast Cancer Patients

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 511 ◽  
Author(s):  
Viktor Hlavac ◽  
Maria Kovacova ◽  
Katerina Elsnerova ◽  
Veronika Brynychova ◽  
Renata Kozevnikovova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Cytotoxic Therapy ◽  
Free Survival ◽  
Testing Phase ◽  
Major Allele Frequency ◽  
Set Up ◽  
Disease Free

The aim of our study was to set up a panel for targeted sequencing of chemoresistance genes and the main transcription factors driving their expression and to evaluate their predictive and prognostic value in breast cancer patients. Coding and regulatory regions of 509 genes, selected from PharmGKB and Phenopedia, were sequenced using massive parallel sequencing in blood DNA from 105 breast cancer patients in the testing phase. In total, 18,245 variants were identified of which 2565 were novel variants (without rs number in dbSNP build 150) in the testing phase. Variants with major allele frequency over 0.05 were further prioritized for validation phase based on a newly developed decision tree. Using emerging in silico tools and pharmacogenomic databases for functional predictions and associations with response to cytotoxic therapy or disease-free survival of patients, 55 putative variants were identified and used for validation in 805 patients with clinical follow up using KASPTM technology. In conclusion, associations of rs2227291, rs2293194, and rs4376673 (located in ATP7A, KCNAB1, and DFFB genes, respectively) with response to neoadjuvant cytotoxic therapy and rs1801160 in DPYD with disease-free survival of patients treated with cytotoxic drugs were validated and should be further functionally characterized.

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