Predictive and prognostic values of tumor infiltrating lymphocytes in breast cancers treated with neoadjuvant chemotherapy: A meta-analysis

Li, Shiqi; Zhang, Ying; Zhang, Peigen; Xue, Shuijing; Chen, Yu; Sun, Lin; Rui, Yang

doi:10.1016/j.breast.2022.10.001

Cited by 19 publications

(22 citation statements)

References 54 publications

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“…also reported that approximately one‐third of patients had at least a 30% TILs value. Our published review 18 suggests approximately 42% of patients had a TIL level of exceeding 20%. The sensitivity and specificity were higher for the 20% threshold than for other thresholds.…”

Section: Discussionmentioning

confidence: 91%

Cost‐effectiveness analysis of tumor‐infiltrating lymphocytes biomarkers guiding chemotherapy de‐escalation in early triple‐negative breast cancer

Li,

Liu,

Zhang

et al. 2023

Cancer Medicine

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BackgroundTo accelerate the clinical translation of tumor‐infiltrating lymphocytes (TILs) biomarkers for guiding chemotherapy de‐escalation in early‐stage triple‐negative breast cancer (TNBC), cost‐effectiveness evidence is essential but has not been investigated. We intend to evaluate the cost‐effectiveness of using TILs to guiding chemotherapy de‐escalation in patients with early‐stage TNBC from the perspective of the Chinese health service system.MethodsThe hybrid decision‐tree‐Markov model was designed to compare the cost‐effectiveness of cytotoxic chemotherapy guided by whether TILs assay was performed in 50‐year‐old female patients with early‐stage TNBC over a lifetime horizon. In Strategy (1), if TILs testing was performed, patients with TILs values exceeding 30% could be spared from chemotherapy. In Strategy (2), where no TILs testing was performed, all patients were administered chemotherapy following China's clinical practices. Based on the algorithm built by Guyot, the individual patient data were reconstructed from the published Kaplan–Meier curves, and the survival functions were calculated by parametric methods. Cost estimates were valued in Chinese yuan (as per rates in 2022).ResultsIn 50‐year‐old female patients with early‐stage TNBC, Strategy (1), which employs TILs testing to guide cytotoxic chemotherapy yielded an additional 0.47 quality‐adjusted life years (QALYs) and saved 40,976 yuan, with an incremental cost‐effectiveness ratio (ICER) of −87,182.98 yuan per QALY gained compared with Strategy (2). This indicates that compared with Strategy (2), Strategy (1) is the dominant scheme. The results were sensitive to utility parameters, discount rates, and treatment costs after relapse. At a willingness‐to‐pay threshold of 85,700 yuan (based on GDP per capita) per QALY, the probability of TILs being cost‐effective was almost 100%.ConclusionsThe application of biomarkers (TILs) to guide decisions for chemotherapy de‐escalation is a cost‐effective strategy for early‐stage TNBC patients and deserves to be widely promoted in clinical practice.

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Section: Discussionmentioning

confidence: 91%

Cost‐effectiveness analysis of tumor‐infiltrating lymphocytes biomarkers guiding chemotherapy de‐escalation in early triple‐negative breast cancer

Li,

Liu,

Zhang

et al. 2023

Cancer Medicine

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“…TILs have been shown by others to be correlated to pCR in the HER2 + and TN subtypes, with higher TILs relating to higher pCR rates (12,22). In the ER+/HER2-subtype, the literature is inconclusive.…”

Section: Discussionmentioning

confidence: 99%

“…A large pooled analysis by Denkert et al showed a signi cant positive correlation between TILs and pCR in the ER+/HER2-subtype (22). A different meta-analysis and some other smaller studies did, however, not nd this correlation (12,13,(24)(25)(26). TILs are reported to be less frequent in ER+/HER2-breast cancer compared to the other subtypes (27), which makes it less likely to nd a correlation in smaller groups.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the immunogenic microenvironment of the tumor plays a role in sensitivity to treatment. A high number of tumor in ltrating lymphocytes (TILs) correlates with higher response rates after NAC and better prognosis in the HER2 + and triple negative (TN) subtypes with odds ratios (ORs) of 2.54 (95% CI 1.50-4.29) and 3.67 (95% CI 1.93-6.97) for pCR, respectively) (12). TILs are usually less abundant in ER+/HER2-breast cancer, and con icting results have been reported about the relationship with response to NAC and prognosis after NAC (13).…”

Section: Introductionmentioning

confidence: 99%

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Tumor infiltrating lymphocytes and change in tumor load on MRI to assess response and prognosis after neoadjuvant chemotherapy in breast cancer

Janssen,

Vries,

Janse

et al. 2024

Preprint

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Purpose In this study, we aimed to explore if the combination of tumor infiltrating lymphocytes (TILs) and change in tumor load on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) leads to better assessment of response to neoadjuvant chemotherapy (NAC) in patients with breast cancer, compared to either alone. Methods In 190 NAC treated patients, MRI scans were performed before and at the end of treatment. The percentage of stromal TILs (%TILs) was assessed in pre-NAC biopsies according to established criteria. Prediction models were developed with linear regression by least absolute shrinkage and selection operator (LASSO) and cross validation (CV), with residual cancer burden (RCB) as the dependent variable. Discrimination for pathological complete response (pCR) was evaluated using area under the receiver operating characteristic curves (AUC). We used Cox regression analysis for exploring the association between %TILs and recurrence-free survival (RFS). Results Fifty-one patients reached pCR. In all patients, the %TILs model and change in MRI tumor load model had an estimated CV AUC of 0.69 (95% confidence interval (CI) 0.53–0.78) and 0.69 (95%CI 0.61–0.79), respectively, whereas a model combining the variables resulted in an estimated CV AUC of 0.75 (95% CI 0.66–0.83). In the group with tumors that were ER positive and HER2 negative (ER+/HER2-) and in the group with tumors that were either triple negative or HER2 positive (TN&HER2+) separately, the combined model reached an estimated CV AUC of 0.72 (95%CI 0.60–0.88) and 0.70(95%CI 0.59–0.82), respectively. A significant association was observed between pre-treatment %TILS and RFS (hazard ratio (HR) 0.72 (95% CI 0.53–0.98), for every standard deviation increase in %TILS, p = 0.038). Conclusion The combination of TILs and MRI is informative of response to NAC in patients with both ER+/HER2- and TN&HER2 + tumors.

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“…Furthermore, it has been observed that a high level of TILs prior to the administration of NAC can serve as a reliable indicator for predicting the pathological response in breast cancer patients. [10–12] However, many questions regarding the predictive value of TILs remain unanswered. First, TILs show a diverse distribution in tumor tissues and their predictive effects also differ.…”

Section: Introductionmentioning

confidence: 99%

Predictive value of stromal tumor-infiltrating lymphocytes in patients with breast cancer treated with neoadjuvant chemotherapy: A meta-analysis

Xia,

Zhang,

Jiang

et al. 2024

Medicine

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Background: The predictive value of tumor-infiltrating lymphocytes (TILs) in response to neoadjuvant chemotherapy (NAC) for breast cancer (BC) has received increasing attention. Here, a meta-analysis was conducted to evaluate the correlation between the expression of stromal TILs and pathological complete response (pCR) after NAC in BC patients. Methods: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched online by using a combination of keywords and free words to screen literature on the expression of stromal TILs and pCR after NAC in patients with BC. The data were extracted and evaluated for quality. Relative risk (RR) was used to evaluate the relationship between the expression of stromal TILs before NAC and pCR in BC patients. Meta-analysis was performed with Review Manager 5.3 and STATA 14.0 software. Results: Eleven studies involving 6039 BC patients were included in the meta-analysis. The results showed a generally high expression of stromal TILs in BC patients, and the pCR rate after NAC in BC patients with a high expression of stromal TILs was significantly higher than that in BC patients with a low expression of stromal TILs [RR = 1.83, 95% confidence interval (CI): 1.69–1.97]. Subgroup analysis based on the molecular subtypes of BC showed that the pCR rate was significantly higher in patients with a high expression of stromal TILs in hormone receptor (HR)-positive BC [RR = 3.23, 95% CI: 2.43–4.30], human epidermal growth factor receptor 2 (HER-2)-positive BC [RR = 1.41, 95% CI: 1.25–1.60], and triple-negative BC [RR = 1.70, 95% CI: 1.53–1.90] than in those with a low expression of stromal TILs. Subgroup analysis based on expression threshold showed that the pCR rate was higher in patients with a high expression of stromal TILs than in patients with a low expression of stromal TILs at different expression thresholds (10% [RR = 1.99, 95% CI: 1.55–2.55], 20%/30% [RR = 1.57, 95% CI: 1.37–1.81], 50%/60% [RR = 1.91, 95% CI: 1.73–2.11]. Conclusion: TILs can be used as a predictor of pCR after NAC in patients with BC, and the appropriate high expression threshold of stromal TILs should be selected as the predictive value according to the molecular subtype of BC.

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Predictive and prognostic values of tumor infiltrating lymphocytes in breast cancers treated with neoadjuvant chemotherapy: A meta-analysis

Cited by 19 publications

References 54 publications

Cost‐effectiveness analysis of tumor‐infiltrating lymphocytes biomarkers guiding chemotherapy de‐escalation in early triple‐negative breast cancer

Cost‐effectiveness analysis of tumor‐infiltrating lymphocytes biomarkers guiding chemotherapy de‐escalation in early triple‐negative breast cancer

Tumor infiltrating lymphocytes and change in tumor load on MRI to assess response and prognosis after neoadjuvant chemotherapy in breast cancer

Predictive value of stromal tumor-infiltrating lymphocytes in patients with breast cancer treated with neoadjuvant chemotherapy: A meta-analysis

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