The value of tumor-infiltrating lymphocytes and CD8 expression as a predictor of response to anthracycline-based neoadjuvant chemotherapy in invasive breast carcinoma of no special type

2021 ◽  
pp. 1-6
Author(s):  
Upik A. Miskad ◽  
Rizki A. Rifai ◽  
Rina Masadah ◽  
Berti Nelwan ◽  
Djumadi Ahmad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Breast Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Predictive Value ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Invasive Breast Carcinoma ◽  
Study Results ◽  
Infiltrating Lymphocytes

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.

Tumor-Infiltrating Lymphocyte Volume Is a Better Predictor of Disease-Free Survival Than Stromal Tumor-Infiltrating Lymphocytes in Invasive Breast Carcinoma

2019 ◽  
Vol 152 (5) ◽  
pp. 656-665 ◽  
Author(s):  
Elmira Vaziri Fard ◽  
Yasir Ali ◽  
Xiaohong I Wang ◽  
Karan Saluja ◽  
Michael H Covinsky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Predictive Value ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Tumor Stroma ◽  
Invasive Breast Carcinoma ◽  
Free Survival ◽  
Infiltrating Lymphocytes ◽  
Disease Free

Abstract Objectives Tumor-infiltrating lymphocytes (TILs) have recently emerged as a prognostic factor in breast cancer. In our previous study, we proposed that tumor stroma should also be considered in the calculation of TILs and we introduced tumor infiltration lymphocyte volume (TILV) in triple-negative breast cancer. Methods We assessed the disease-free survival predictive value of TILV in all subtypes of invasive breast carcinoma and compared the predictive value of TILV with TILs. Differences between disease-free survival curves were determined by using the log-rank test, and Kaplan-Meier survival plots were generated for both groups. Results TILV was significantly correlated with disease-free survival in both invasive ductal carcinoma (P = .03) and all subtypes of invasive breast carcinoma (P = .043), whereas TILs failed to show a statistical significance. Conclusions Tumor-stroma ratio needs to be considered in estimation of tumor immunity, and TILV adds more predictive power to TILs.

Predictive value of tumor infiltrating lymphocytes (TIL) for response to breast cancer neoadjuvant chemotherapy (NCT).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 585-585
Author(s):  
Elena Garcia-Martinez ◽  
Gines Luengo-Gil ◽  
Asuncion Chaves ◽  
Lorena Velazquez ◽  
Enrique Gonzalez-Billalabeitia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Predictive Value ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Residual Tumor ◽  
Complete Response ◽  
Before And After ◽  
Pre Treatment ◽  
Infiltrating Lymphocytes

585 Background: The association of tumor microenvironment immune response with outcome after breast cancer (BC) NCT has been suggested by several studies. However, the relevance of each TIL subpopulation is still controversial. The objective of this study was to evaluate the predictive and prognostic value of TIL before and after NCT in patients with BC. Methods: We analyzed TIL and CD68 cells in pre- and post-chemotherapy biopsies of BC patients treated with NCT (80.4% sequential AC-docetaxel). A tissue microarray with paired pre- and post-NCT biopsies was built, and stained with immunohistochemistry (IHC) for CD3, CD4, CD8, CD20, FOXP3 and CD68. Morphometric analysis (TIL count/mm2) was performed after slide scanning and digitalization. Results: We included 121 consecutive patients with invasive BC, most of them with stages IIB (28%) or IIIA-C (56.4%). IHC phenotype: 50.4% Her2- hormone-sensitive (HS), 13.2% Her2+ HS, 10.7% Her2+ non-HS, and 21.5% triple negative. Pathologic complete response (pCR): 17.4%. Median overall survival (OS) and disease free survival (DFS) has not been reached (median follow-up: 60 months). Higher than median pre-NCT TIL infiltration was predictive of pCR to NCT: CD3 > 172/mm2 (p=0.001; Hazard Ratio [HR]: 9,61, 95% confidence interval [95%CI] 2.49–37.02); CD4 > 67/mm2 (p=0.001; HR: 8.82, 95%CI 2.43–31.96); CD20 > 42/mm2 (p=0.001; HR: 8.71, 95%CI 2.31–32.74). Logistic regression multivariate models including grade and IHC phenotype confirmed the independent predictive value of higher pre-NCT CD3, CD4, and CD20 for pCR. In the group of patients with HS Her2- BC without pCR (n=44), higher infiltration (cut-point: median value) by some TIL subpopulations and by CD68 cells in post-NCT residual tumor associated to lower DFS: CD8 > 37/mm2 (log-rank; p=0.04), CD20 > 14/mm2 (p=0.07) and CD68> 39/mm2 (p=0.06). Conclusions: Higher pre-treatment CD3, CD4 and CD20 TIL predicted pRC in patients with invasive BC receiving anthracyclines and taxanes NCT, while higher infiltration of residual tumor by CD8 associated to worse DFS in patients with HS Her2- BC without pCR after NCT. TIL might be useful as predictive factors in the setting of NCT for BC [Supported by GEICAM-Beca Ana Balil].

scholarly journals Outcome Prediction after Neoadjuvant Chemotherapy (NAC) for Breast Cancer, using Tumor-Infiltrating Lymphocytes within Fibrotic Foci of Tumor Stroma (FF-TILs)

2021 ◽  
Author(s):  
Yuka Asano ◽  
Shinichiro Kashiwagi ◽  
Rika Kouhashi ◽  
Akimichi Yabumoto ◽  
Koji Takada ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Multivariable Analysis ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Tumor Stroma ◽  
Hormone Receptor Positive ◽  
Close Relationship ◽  
Infiltrating Lymphocytes

Abstract Background: Tumor-infiltrating lymphocytes (TILs), which are indicators for monitoring an immune response, are generally mononuclear immunocytes that aggregate with tumors and are thought to have a close relationship with cancer cells. On the other hand, a fibrotic focus (FF) within the stroma of a tumor is a histological formation that plays an important role in the cancer microenvironment with regard to proliferation and development. Here, we focus on TILs that exist within the FF and we have performed pathological evaluations.Methods: Of the 320 patients were treated with neoadjuvant chemotherapy (NAC), 239 subjects who were able to evaluate FF-TILs were targeted. Lymphocytes that infiltrate the FF are FF-TILs.Results: The disease-free survival (DFS) period after NAC for the high-FF-TIL group was found to be significantly longer than that for the low-FF-TIL group for all cases (p < 0.001) and for all subtypes of triple-negative breast cancer (TNBC) (p = 0.001), human epidermal growth factor receptor 2-enriched breast cancer (HER2BC) (p = 0.010), and hormone receptor-positive breast cancer (HRBC) (p = 0.003). In multivariable analysis as well, high-FF-TIL group classification was an independent factor for recurrence after NAC for all cases (p < 0.001, hazard ratio (HR) = 0.198) and all subtypes of TNBC (p = 0.006, HR = 0.172), HER2BC (p = 0.025, HR = 0.135), and HRBC (p = 0.007, HR = 0.228).Conclusions: It is suggested that FF-TILs are a useful factor for predicting recurrence of breast cancer after NAC.Article headings: NAC for breast cancer by evaluation of FF-TILs

Predictive and prognostic value of tumor-infiltrating lymphocytes in breast cancer treated with neoadjuvant chemotherapy.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 128-128 ◽  
Author(s):  
Akiko Matsumoto ◽  
Hiromitsu Jinno ◽  
Kunihiko Hiraiwa ◽  
Tetsuya Nakamura ◽  
Junichi Saito
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Pearson Correlation ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Her2 Positive ◽  
Median Percentage ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Infiltrating Lymphocytes

128 Background: The prognostic importance of tumor-infiltrating lymphocytes (TILs) in triple-negative (TN) and HER2-positive breast cancer has been suggested in recent trials. The aim of this study is to evaluate a relationship between TILs and response to neoadjuvant chemotherapy (NAC) as well as long-term outcome in breast cancer including luminal, TN and HER2 subtypes. Methods: Twenty-seven patients receiving NAC from January 2010 to March 2015 at Inagi Municipal Hospital were analyzed. Intratumoral lymphocytes (ItuLy) and stromal lymphocytes (StrLy) were evaluated in hematoxylin and eosin-stained sections from pretherapeutic core needle biopsies. Lymphocyte-predominant breast cancer (LPBC) was defined as tumors with > 50% of ItuLy or StrLy. Results: A total of 27 patients were divided into 13 luminal (48.1%), 3 TN (11.1%) and 11 HER2 (40.7%) subtypes. The median age was 58 years and the median tumor size was 3.0 cm. A significant correlation between ItuLy (the median percentage: 5%) and StrLy (25%) was observed (Pearson correlation coefficient = 0.628, P< 0.01). LPBC comprised 29.6% (8/27) of total population, with higher frequencies of 33.3% and 54.5% in the TN and HER2-positive subtypes, when compared with 7.7% in luminal subtype (P= 0.044). LPBC group had a significantly higher pathological complete response (pCR) rate of 62.5% (5/8), compared with 5.3% (1/19) for non-LPBC group (P= 0.004). LPBC showed the modest correlation with pCR in luminal (100% (1/1) vs. 0% (0/12), P= 0.077) and HER2-positive subtypes (66.6% (4/6) vs. 25% (1/5), P= 0.175). In TN subtype, neither LPBC nor non-LPBC showed pCR. After a median follow-up of 24.3 months, patients with any TILs were significantly associated with better disease-free survival (DFS) than those without TILs (24.3 vs. 23.6 months, P= 0.016). The most significant impact of TILs on DFS was observed in HER2-positive subtype (23.2 vs. 15.2 months, P= 0.046), whereas TILs did not associate with DFS in luminal and TN subtypes. Conclusions: The presence of TILs was a significant predictor for response to NAC and would provide useful information of prognosis in breast cancer.

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