Evaluation of tumor-infiltrating lymphocytes and association with prognosis in <i>BRCA</i>-mutated breast cancer

Sønderstrup, Ida Marie Heeholm; Jensen, Maj Britt; Ejlertsen, Bent; Eriksen, Jens Ole; Gerdes, Anne; Kruse, Torben A.; Larsen, Martin Jakob; Thomassen, Mads; Lænkholm, Anne‐Vibeke

doi:10.1080/0284186x.2018.1539239

Cited by 26 publications

(27 citation statements)

References 35 publications

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“…TIL density was more intense in tumors from young compared to elderly patients, which may be attributed to the generally accepted decline in the immune system efficiency with progressing age. A further reason for tumors in the young being more TIL-rich could be the underlying germline BRCA1 background in some of the patients (31), which, although suspected, cannot be proven in our case. The diverse association of TP53 mutations with TIL density, which was prominent in the elderly but not in the young patients, may be related to different mutagenic processes operating in the two age groups (32).…”

Section: Discussionmentioning

confidence: 61%

Tumor Mutational Patterns and Infiltrating Lymphocyte Density in Young and Elderly Patients With Breast Cancer

Nikolaidi

Kotoula

Koliou

et al. 2020

Cancer Genomics Proteomics

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Background/Aim: Age may pertain to different tumor genotype characteristics which may interfere with treatment efficacy and prognosis. We investigated the distribution and prognostic effect of mutations and tumor infiltrating lymphocyte (stromal TIL density) in young (≤35 years) and elderly (>65 years) early breast cancer patients. Materials and Methods: Paraffin tumor genotypes of all clinical subtypes from 345 patients were examined. Results: A total of 638 mutations were detected in 221 patients (64.1%). Compared to young, elderly patients presented with lower TIL density (p<0.

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Section: Discussionmentioning

confidence: 61%

Tumor Mutational Patterns and Infiltrating Lymphocyte Density in Young and Elderly Patients With Breast Cancer

Nikolaidi

Kotoula

Koliou

et al. 2020

Cancer Genomics Proteomics

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“…For patients with BRCA 1 and 2 mutations, TILs proved itself to be a favorable factor of disease-free survival. For overall survival, for each 10% increase of TILs, it was demonstrated a 10% reduction in mortality for BRCA 1 carriers, with no significative effect on BRCA 2 mutation patients [46]. We demonstrated the predictive value of TILs in lymph nodes status for all intrinsic subtypes, with significative differences regarding only the response to NAC.…”

Section: Discussionmentioning

confidence: 71%

Can Tumor-Infiltrating Lymphocytes (TILs) Be a Predictive Factor for Lymph Nodes Status in Both Early Stage and Locally Advanced Breast Cancer?

Caziuc¹,

Schlanger²,

Amarinei³

et al. 2019

JCM

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The status of axillary lymph nodes is an important prognostic factor in the outcome of breast cancer tumors. New trials changed the attitude towards axillary clearance. In the era of development of new immune therapies for breast cancer, it is important to identify a biomarker that can predict lymph node status. Tumor-infiltrating lymphocytes (TILs) are a valuable indicator of the immune microenvironment that plays the central role in new anticancer drugs. Although the correlation between TILs and response to chemotherapy was established by previous studies, our retrospective study investigated the correlation between TILs and lymph node status. We analyzed data on 172 patients. According to stage, patients were divided in two groups: patients who underwent primary surgical treatment (breast-conserving or mastectomy and sentinel lymph node (SLN) biopsy +/− axillary clearance in conformity with lymph node status) and patients who received chemotherapy prior to surgical treatment (breast-conserving or mastectomy + axillary clearance). We showed a good inverse correlation between TILs and lymph nodes status for both early stage and locally advanced breast cancers. Moreover, TILs are a predictor for positive lymph nodes in the axilla in patients undergoing axillary clearance after SLN biopsy, with no statistical difference between the intrinsic or histological subtype of breast cancers. We also obtained a significant correlation between TILs and response to chemotherapy with no significative difference according to histological subtype. Although further data have still to be gathered before meeting the criteria for clinical utility, this study demonstrates that TILs are one of the most accredited forthcoming biomarkers for breast cancer (BC) patients.

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“…Next, 49 articles remained for full-text assessment due to 343 citations being excluded via title and abstract screening; of these, studies that were reviews (n = 2), inconsistent to the criteria of the high-level TILs in our study (n = 4), devoid of useful data (n = 16) and centered on PD-L1 + TILs (n = 3) or FOXP3+ TILs (n = 2) did not meet the inclusion criteria and hence were excluded. Ultimately, 22 qualified studies were included for meta-analysis (Table 1) [5,6,[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. The procedure of qualified article selection is outlined in Fig.…”

Section: Search Resultsmentioning

confidence: 99%

Association between levels of tumor-infiltrating lymphocytes in different subtypes of primary breast tumors and prognostic outcomes: a meta-analysis

Wang

et al. 2020

BMC Women's Health

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Background To investigate the impact of the elevation of tumor-infiltrating lymphocytes (TILs) in different molecular subtypes of primary breast cancer, i.e. each 10% increment of TILs and high-level TILs (TILs≥50%) in tumor, on overall survival (OS) and pathological complete response (pCR) and to compare the presentation of high-level TILs across these molecular subtypes. Methods Citation retrieval was performed in the PubMed, Cochrane Library, Embase and Web of Science databases. All statistical calculations were performed by the software of StataSE version 12.0. Results Twenty-two eligible clinical trials including 15,676 unique patients were included for meta-analysis. Each 10% increment of TILs significantly improved OS in human epidermal growth factor receptor 2 (HER2)-overexpression (pooled Hazard ratio (HR), 0.92; 95% CI, 0.89–0.95) and triple-negative (TN) (pooled HR, 0.90; 95% CI, 0.89–0.92) breast tumors but not in luminal tumor subtype (pooled HR, 1.06; 95% CI, 0.99–1.13). It was also associated with an increased pCR rate in breast cancers (pooled Odds ratio (OR), 1.27; 95% CI, 1.19–13.5). High-level TILs were significantly related with a higher pCR rate (pooled OR, 2.73; 95% CI, 2.40–3.01) than low-level TILs. The HER2-amplified (pooled OR, 3.14; 95% CI, 1.95–5.06) and TN (pooled OR, 4.09; 95% CI, 2.71–6.19) phenotypes of breast cancers expressed significantly more high-level TILs than the luminal tumor subtype, although the presentation of those between the former two subsets was not significantly different (pooled OR, 1.30; 95%CI, 0.83–2.04). Conclusions The elevation of TILs in breast tumors predicts favorable prognostic outcomes, particularly in the HER2-overexpression and TN subtypes.

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Evaluation of tumor-infiltrating lymphocytes and association with prognosis in BRCA-mutated breast cancer

Cited by 26 publications

References 35 publications

Tumor Mutational Patterns and Infiltrating Lymphocyte Density in Young and Elderly Patients With Breast Cancer

Tumor Mutational Patterns and Infiltrating Lymphocyte Density in Young and Elderly Patients With Breast Cancer

Can Tumor-Infiltrating Lymphocytes (TILs) Be a Predictive Factor for Lymph Nodes Status in Both Early Stage and Locally Advanced Breast Cancer?

Association between levels of tumor-infiltrating lymphocytes in different subtypes of primary breast tumors and prognostic outcomes: a meta-analysis

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