Tumor-infiltrating lymphocytes are significantly associated with better overall survival and disease-free survival in triple-negative but not estrogen receptor–positive breast cancers

2017 ◽  
Vol 64 ◽  
pp. 7-12 ◽  
Author(s):  
Uma Krishnamurti ◽  
Ceyda Sonmez Wetherilt ◽  
Jing Yang ◽  
Limin Peng ◽  
Xiaoxian Li
2019 ◽  
Vol 37 (7) ◽  
pp. 559-569 ◽  
Author(s):  
Sherene Loi ◽  
Damien Drubay ◽  
Sylvia Adams ◽  
Giancarlo Pruneri ◽  
Prudence A. Francis ◽  
...  

Purpose The aim of the current study was to conduct a pooled analysis of studies that have investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) in early-stage triple negative breast cancer (TNBC). Methods Participating studies had evaluated the percentage infiltration of stromally located TILs (sTILs) that were quantified in the same manner in patient diagnostic samples of early-stage TNBC treated with anthracycline-based chemotherapy with or without taxanes. Cox proportional hazards regression models stratified by trial were used for invasive disease-free survival (iDFS; primary end point), distant disease-free survival (D-DFS), and overall survival (OS), fitting sTILs as a continuous variable adjusted for clinicopathologic factors. Results We collected individual data from 2,148 patients from nine studies. Average age was 50 years (range, 22 to 85 years), and 33% of patients were node negative. The average value of sTILs was 23% (standard deviation, 20%), and 77% of patients had 1% or more sTILs. sTILs were significantly lower with older age ( P = .001), larger tumor size ( P = .01), more nodal involvement ( P = .02), and lower histologic grade ( P = .001). A total of 736 iDFS and 548 D-DFS events and 533 deaths were observed. In the multivariable model, sTILs added significant independent prognostic information for all end points (likelihood ratio χ2, 48.9 iDFS; P < .001; χ2, 55.8 D-DFS; P < .001; χ2, 48.5 OS; P < .001). Each 10% increment in sTILs corresponded to an iDFS hazard ratio of 0.87 (95% CI, 0.83 to 0.91) for iDFS, 0.83 (95% CI, 0.79 to 0.88) for D-DFS, and 0.84 (95% CI, 0.79 to 0.89) for OS. In node-negative patients with sTILs ≥ 30%, 3-year iDFS was 92% (95% CI, 89% to 98%), D-DFS was 97% (95% CI, 95% to 99%), and OS was 99% (95% CI, 97% to 100%). Conclusion This pooled data analysis confirms the strong prognostic role of sTILs in early-stage TNBC and excellent survival of patients with high sTILs after adjuvant chemotherapy and supports the integration of sTILs in a clinicopathologic prognostic model for patients with TNBC. This model can be found at www.tilsinbreastcancer.org .


2018 ◽  
Vol 33 (4) ◽  
pp. 467-474 ◽  
Author(s):  
Younghoon Kim ◽  
Xianyu Wen ◽  
Nam Yun Cho ◽  
Gyeong Hoon Kang

Background: The prognostic value of immune cells expressing programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) in cancer are controversial, and the potential differential impact of using tissue microarrays and whole tissue sections to assess the positivity of immune cells has not been addressed. Methods: The current study included 30 eligible studies with 7251 patients that evaluated the relationship between tumor-infiltrating lymphocytes expressing PD-1/PD-L1 and overall survival and disease-free survival, or progression-free survival. Subgroup analysis was based on the tissue type of cancer and the type of tissue sampling (tissue microarray or whole tissue section). Results: In the meta-analysis, PD-1-positive and PD-L1-positive tumor-infiltrating lymphocytes had a positive effect on disease-free survival or progression-free survival (hazard ratio [HR] 0.732; 95% confidence interval [CI] 0.565, 0.947; and HR 0.727; 95% CI 0.584, 0.905, respectively). PD-L1-positive tumor-infiltrating lymphocytes had a positive impact on overall survival in studies using tissue microarray (HR 0.586; 95% CI 0.476, 0.721), but had a poor impact when only whole tissue sections were considered (HR 1.558; 95% CI 1.232, 1.969). Lung cancer was associated with good overall survival and disease-free survival (HR 0.639; 95% CI 0.491, 0.831; and HR 0.693; 95% CI 0.538, 0.891, respectively) for PD-1-positive tumor-infiltrating lymphocytes, and colorectal cancer showed favorable disease-free survival (HR 0.471; 95% CI 0.308, 0.722) for PD-L1-positive tumor-infiltrating lymphocytes. Conclusion: Immune cells expressing PD-1 and PD-L1 within tumors are associated with the prognosis. However, the correlation may vary among different tumor types and by the type of tissue sampling used for the assessment.


2010 ◽  
Vol 63 (8) ◽  
pp. 744-747 ◽  
Author(s):  
Rutika Mehta ◽  
Rohit K Jain ◽  
Nour Sneige ◽  
Sunil Badve ◽  
Erika Resetkova

One-fifth of breast cancers have the triple-negative phenotype; a good prognostic marker has yet not been described for these tumours. Tumour microarrays from 58 triple-negative patients treated with surgery followed by chemotherapy were analysed for expression of cytokeratin 5/6 (CK5/6), epidermal growth factor receptor (EGFR), vimentin, p63 and cytokeratin 34βE12. The mean patient age was 59.2 years with a follow-up from 39 to 168 months. Clinicopathological variables and survival data were correlated with biomarker expression. The frequency of expression of cytokeratin 5/6, EGFR, vimentin, p63 and 34βE12 was 33%, 65%, 50%, 19% and 85%, respectively. Each of 34βE12, p63, EGFR and T stage significantly correlated with both disease-free survival and overall survival. T stage and 34βE12 were independent predictors of overall survival in a multivariate analysis. Expression of 34βE12 predicts disease-free and overall survival in patients with triple-negative tumours. Additional studies are planned to confirm these initial findings.


2021 ◽  
Author(s):  
Jie-Yu Zhou ◽  
Kang-Kang Lu ◽  
Wei-Da Fu ◽  
Hao Shi ◽  
Jun-Wei Gu ◽  
...  

Background: Triple-negative breast cancer (TNBC) is an aggressive disease. Nomograms can predict prognosis of patients with TNBC. Methods: A total of 745 eligible TNBC patients were recruited and randomly divided into training and validation groups. Endpoints were disease-free survival and overall survival. Concordance index, area under the curve and calibration curves were used to analyze the predictive accuracy and discriminative ability of nomograms. Results: Based on the training cohort, neutrophil-to-lymphocyte ratio, positive lymph nodes, tumor size and tumor-infiltrating lymphocytes were used to construct a nomogram for disease-free survival. In addition, age was added to the overall survival nomogram. Conclusion: The current study developed and validated well-calibrated nomograms for predicting disease-free survival and overall survival in patients with TNBC.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22219-e22219
Author(s):  
B. S. Ajaikumar ◽  
R. Rao ◽  
J. Prabhu ◽  
J. D. Kulkarni ◽  
P. K ◽  
...  

e22219 Background: Triple-negative (ER-negative, PR-negative, HER2/neu negative) breast cancer has distinct clinical and pathologic features, and is a clinical problem because of its typically high grade, relatively poor prognosis, aggressive behavior and lack of targeted therapies leaving chemotherapy as the mainstay of treatment. This study envisaged to analyse the influence of triple negativity status on survival and disease free survival in prospective cohort of breast cancer patients. Methods: Breast tumors of 215 women aged 30–75, diagnosed from 2004 were tested for ER, PR and HER2 positivity by immunohistochemistry and correlated with clinical outcomes such as recurrence, disease free survival and overall survival using Kaplan Meiers Survival analysis and Coxs regression analysis. The study cohort was followed up for 60 months or until death whichever was earlier. Results: Triple negativity significantly influenced disease free survival (46 ± 3, 41, 52) vs. non triple negative cohort (mean ± SE; 95%CI, 37 ± 2; 32, 40) and log rank = 2.1, p = 0.04. However triple negativity did not influence overall survival in months (56 ± 0; 55, 56) vs. non triple negative cohort (43 ± 1; 42, 45), (log rank = 1.78, p = 0.16). However, the mean disease free survival was (45 ± 7; 32, 58) months for patients >40 years age vs (37 ± 4; 33, 39) for patients < 40 years of age (log rank = 2.87, p =0.02). Stage of disease, node status, grade and menopausal status did not influence disease free survival significantly. However, Cox regression analysis did not predict significant effects of triple negativity on overall survival or disease free survival when controlled for confounding factors such as age, node status, stage etc Conclusions: Our observations suggest that triple negativity can significantly affect progression of breast cancer in Indian breast cancer patients and longer follow up is necessary (10 years) to determine its effects on survival. No significant financial relationships to disclose.


2003 ◽  
Vol 21 (6) ◽  
pp. 976-983 ◽  
Author(s):  
I. Craig Henderson ◽  
Donald A. Berry ◽  
George D. Demetri ◽  
Constance T. Cirrincione ◽  
Lori J. Goldstein ◽  
...  

Purpose: This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival. Patients and Methods: After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 mg/m2, with one of three doses of doxorubicin (A), 60, 75, or 90 mg/m2, for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m2. Tamoxifen was given to 94% of patients with hormone receptor–positive tumors. Results: There was no evidence of a doxorubicin dose effect. At 5 years, disease-free survival was 69%, 66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m2, respectively. The hazard reductions from adding paclitaxel to CA were 17% for recurrence (adjusted Wald χ2 P = .0023; unadjusted Wilcoxon P = .0011) and 18% for death (adjusted P = .0064; unadjusted P = .0098). At 5 years, the disease-free survival (± SE) was 65% (± 1) and 70% (± 1), and overall survival was 77% (± 1) and 80% (± 1) after CA alone or CA plus paclitaxel, respectively. The effects of adding paclitaxel were not significantly different in subsets defined by the protocol, but in an unplanned subset analysis, the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 (95% confidence interval, 0.59 to 0.86) for those with estrogen receptor–negative tumors and only 0.91 (95% confidence interval, 0.78 to 1.07) for patients with estrogen receptor–positive tumors, almost all of whom received adjuvant tamoxifen. The additional toxicity from adding four cycles of paclitaxel was generally modest. Conclusion: The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer.


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