scholarly journals Predictive and prognostic significance of CD8+ tumor-infiltrating lymphocytes in patients with luminal B/HER 2 negative breast cancer treated with neoadjuvant chemotherapy

2017 ◽  
Vol 14 (1) ◽  
pp. 337-344 ◽  
Author(s):  
Khalid Al-Saleh ◽  
Nashwa Abd El-Aziz ◽  
Arwa Ali ◽  
Waleed Abozeed ◽  
Ahmed Abd El-Warith ◽  
...  
2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 559-559
Author(s):  
M. Ono ◽  
H. Tsuda ◽  
C. Shimizu ◽  
S. Yamamoto ◽  
T. Shibata ◽  
...  

559 Background: Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptor (ER), progesterone receptor (PgR) and HER-2. Pathological complete response (pCR) of TNBC to neoadjuvant chemotherapy (NAC) is correlated with excellent clinical outcome. We examined the value of histological parameters including tumor-infiltrating lymphocytes (TIL) and tumor cell apoptosis as surrogate markers for pCR in TNBC. Methods: Of 474 patients who received NAC and subsequent surgical therapy to stage II-III invasive breast carcinoma between 1999 and 2007, 102 (22%) had TNBC, and 92 core needle biopsy (CNB) specimens before NAC were available. We first immunohistochemically confirmed TNBC and basal-like subtype by current criteria for ER, PgR, and HER-2, cytokeratin (CK) 5/6, CK14, EGFR, and p53. All cases were TNBC, and 54 tumors (59%) were basal-like subtype defined as expression of at least one of CK5/6, CK14 and EGFR in >1% of cancer cells. Totally, 26 tumors (28%) showed pCR. Thirteen histopathological parameters were examined, and their correlation with pCR rate was tested. These parameters were also examined in resected tumor specimens from 21 non-pCR cases. Results: The pCR rate was significantly higher in the patients with tumors with TIL (24 of 68, 35%) than in those without (2 of 24, 8%, p = 0.01), and higher in tumors with high-score apoptosis (9 of 19, 47%) than in those with low-score apoptosis (17 of 73, 23%, p = 0.04). Tumors showing medullary features and p53-negative tended to show pCR more frequently (38% and 35%) than those with non-medullary features and with p53-positive (25% and 24%), but the differences were not significant. Of 21 non-pCR cases, TIL was consistently negative before and after NAC in 8, but TIL emerged after NAC in 13. The pCR rate did not differ significantly between the basal-like type (31%) and non-basal-like type (24%). Conclusions: TIL and the level of tumor cell apoptosis appeared predictive markers for response to NAC in TNBC. Patients’ host factors correlated with immune response appears play a substantial role in the response to NAC in TNBC. No significant financial relationships to disclose.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12654-e12654
Author(s):  
Katia MERCEDES Roque ◽  
Marco Galvez Nino ◽  
Carlos Arturo Castaneda Altamirano ◽  
Miluska Castillo Garcia ◽  
Joselyn Sanchez ◽  
...  

e12654 Background: The response after neoadjuvant chemotherapy (NAC) is the main prognostic factor in breast cancer (BC), likewise, malnutrition, anemia and systemic inflammation have also been associated to prognosis in breast cancer. We evaluated the association between pathological response (PR) and tumor infiltrating lymphocytes (TILs) post NAC with nutritional predictors as body mass index (BMI), prognostic nutritional index (PNI), anemia and neutrophil/lymphocyte index (N/L). Methods: This is a retrospective analysis of women diagnosed with BC between 2006 to 2017 at Instituto Nacional de Enfermedades (INEN) who received NAC. Pathological response was classified through residual cancer burden (RCB) and TILs post NAC which were prospectively evaluated by a pathologist. Clinical and pathological features as well as survival status were obtained from patient files. Results: We identified 439 women with BC who received NAC. Median age was 49 years, histological grade 3 was found in 245 patients (55.8%) and stage IIIB was the most frequent at diagnosis with 257 patients (58.5%). Luminal B subtype was the most frequent (43.7%). Rate of pCR was 10.5% and median TILs post NAC was 20%. About nutritional predictors, we use the median as a cutoff to discriminate between high and low values, for BMI was 27.5, for PNI was 56, for hemoglobin was 13.2 and for NLR was 1.84. There was no association for TILs post NAC with BMI (p = 0.38), PNI (p = 0.057) and hemoglobin (p = 0.43). We found a positive association between ILN and TILs post NAC (p = 0.001). On the other hand, we don’t found association for RCB with BMI (p = 0.45), PNI (p = 0.641), ILN (p = 0.2) and hemoglobin (p = 0.15). In the multivariate analysis, only RCB was an independent predictor for DFS (95 % CI, 87-100.5; p = 0.00001) and OS (95 % CI, 101.8-114.1; p = 0.00001). There was no association between BMI, PNI, ILN and anemia with OS and DFS. For the TILs post NAC there was a tendency to association with DFS (p = 0.07) and OS (p = 0.07). Conclusions: There are association between neutrophil/lymphocyte index with TILs after NAC. There was no association between nutritional and systemic predictors with long-term outcomes. The pathologic response is a biomarker for predicting the long-term outcomes of breast cancer patients.


2020 ◽  
Author(s):  
Jing Zhang ◽  
Mustapha Abubakar ◽  
pei Yuan ◽  
Hela Koka ◽  
Lei Guo ◽  
...  

Abstract BackgroundTumor-infiltrating lymphocytes (TILs) have strong prognostic values in triple-negative and HER2-enriched breast cancer, but their prognostic roles in luminal breast cancer (LBC) are less clear. Here, we assessed the overall TILs levels and CD8+ T-cells in relation to the prognosis of LBC patients from China.Methods A total of 596 patients with LBC who were premenopausal and treated with adjuvant endocrine therapy were included. Among them, 160 cases were evaluated for CD8 by immunohistochemical (IHC) staining. Whole-section hematoxilyn and eosin and IHC staining were visually assessed for stromal TILs (sTILs), stromal CD8+ T-cells (sCD8) and intratumoral CD8+ T-cells (iCD8). Multivariable Cox proportional hazards model were used to test the associations between TILs and disease-free survival (DFS) and overall survival (OS) with the adjustment of clinicopathologic characteristics and treatment. ResultsHigh sTILs (≥10%) were associated with high histologic grade (p<0.001), luminal B/HER2- (p<0.001), luminal B/HER2+ subtype (p=0.002), and high Ki67 expression (≥25%; p=0.014). Similar associations were observed for sCD8 but not for iCD8. While sTILs and sCD8 were not associated with either DFS or OS, the presence of iCD8 (≥1%) was associated with better DFS in both univariate (HR=0.51, 95%CI 0.26-0.96, p=0.042) and multivariate (HR=0.48, 95%CI 0.25-0.92, p=0.027) analyses. Similar but less significant associations were found for iCD8 and OS (adjusted HR=0.35, 95%CI 0.11-1.10, p=0.073).Conclusions Among Chinese premenopausal patients with LBC, iCD8 demonstrated suggestive associations with favorable outcomes. In contrast, although sTILs and sCD8 were associated with more aggressive tumor features, they did not appear to be associated with clinical outcomes.


2020 ◽  
Author(s):  
Shiqi Li ◽  
Ying Zhang ◽  
Shujun Wang ◽  
Rui Yang

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.


2021 ◽  
pp. 1-6
Author(s):  
Upik A. Miskad ◽  
Rizki A. Rifai ◽  
Rina Masadah ◽  
Berti Nelwan ◽  
Djumadi Ahmad ◽  
...  

BACKGROUND: The immune system is known to play an important role in tumor cell eradication. Although cancer cells were able to escape from the immune system, many studies showed mononuclear inflammatory cell infiltrates known as tumor-infiltrating lymphocytes (TILs) on breast cancer histopathology specimens showed better prognosis, including in disease-free survival (DFS) and chemotherapy responses. OBJECTIVE: This study aimed to reveal the predictive value of tumor-infiltrating lymphocytes (TILs) levels and CD8 expression in invasive breast carcinoma of no special type patients’ samples on response to anthracycline-based neoadjuvant chemotherapy. METHODS: 75 pre-treatment biopsy samples that were diagnosed as invasive breast carcinoma of no special type were evaluated. TILs level determined following recommendations of International TILs Working Group 2014, CD8 expression assessed semiquantitatively after immunohistochemistry staining. Response to anthracycline-based neoadjuvant chemotherapy evaluated clinically using Response Evaluation Criteria in Solid Tumours (RECIST) criteria and pathologically by evaluating hematoxylin and eosin (H&E)-stained slides from mastectomy specimens after 3 or 4 cycles of neoadjuvant chemotherapy. RESULTS: Chi-squared analysis showed a significant relationship between TILs level and CD8 expression with chemotherapy responses clinically (p = 0.011 and p = 0.017 respectively) but not pathologically. Furthermore, the logistic regression test exhibit the predictive value of TILs level was 66.7% and CD8 expression was 64%. CONCLUSIONS: This study results suggest that TILs level and CD8 expression may be added as predictive factors to the response of anthracycline-based neoadjuvant chemotherapy, and oncologists may take benefit in breast cancer patient’s management.


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