Abstract
BackgroundWhether tumour-infiltrating lymphocytes (TILs) play different roles in different molecular subtypes of breast cancer remains unknown. Additionally, their prognostic and predictive value in different molecular subtypes of breast cancer is still controversial. The aim of our meta-analysis was to assess the prognostic and predictive value of TILs in different molecular subtypes of breast cancer by summarizing all relevant studies performing multivariate analysis.MethodsPubMed, Embase, EBSCO, ScienceDirect, the Cochrane Database and Web of Science were comprehensively searched (until March 2020). Hazard ratios (HRs), odds ratios (ORs) and their 95% confidence intervals (CIs) were used as effect measures to perform our meta-analysis. A random effect model was used. Stata software, version 15 (2017) (StataCorp, College Station, TX, USA) was used to perform the statistical analysis.ResultsThirty-three studies including 18,170 eligible breast cancer patients were analysed. The meta-analysis showed that high TIL expression was significantly associated with increased pathological complete response (pCR) rates after neoadjuvant chemotherapy in patients with the HER2-enriched molecular subtype (OR = 1.137, 95% CI [1.061 ~ 1.218], p < 0.001) and triple-negative breast cancer (TNBC) subtype (OR = 1.120, 95% CI [1.061 ~ 1.182], p < 0.001). However, high TIL expression was not significantly associated with high pCR rates after neoadjuvant chemotherapy in patients with the luminal molecular subtype of breast cancer (OR = 1.154, 95% CI [0.789 ~ 1.690], p = 0.460). We carried out a meta-analysis on the HRs of overall survival (OS) and disease-free survival (DFS) to assess the prognostic value of TILs in breast cancer with different molecular subtypes more deeply. Our meta-analysis confirmed that high TILs were associated with significantly improved DFS in patients with the HER2-enriched molecular subtype [HR = 0.940, 95% CI (0.903 ~ 0.979), p = 0.003] and TNBC molecular subtype [HR = 0.907, 95% CI (0.862 ~ 0.954), p < 0.001]. However, high TILs were not associated with significantly better DFS in patients with the luminal molecular subtype of breast cancer [HR = 0.998, 95% CI (0.977 ~ 1.019), p = 0.840]. Furthermore, the results confirmed that high TILs were significantly related to better OS in patients with the HER2-enriched molecular subtype [HR = 0.910, 95% CI (0.866 ~ 0.957), p < 0.001] and TNBC molecular subtype [HR = 0.869, 95% CI (0.836 ~ 0.904), p < 0.001]. Conversely, the summarized results indicated that high TILs were significantly associated with poor OS in patients with the luminal molecular subtype of breast cancer [HR = 1.077, 95% CI (1.016 ~ 1.141), p = 0.012].ConclusionsOur meta-analysis confirms that high TILs are associated with favourable survival and predicts pCR in breast cancer patients with the TNBC and HER2-enriched molecular subtypes.
Highlights
Whether tumour-infiltrating lymphocytes (TILs) play different roles in different molecular subtypes of breast cancer remains unknown
Our meta-analysis confirms that high TILs are associated with favourable survival and predicts pathological complete response (pCR) in breast cancer patients with the triple-negative breast cancer (TNBC) and Human epidermal growth factor receptor-2 (HER2)-enriched molecular subtypes
Selection standards To ensure the accuracy and reliability of our analysis, we selected qualified studies based on the following criteria. (i) The prognostic or predictive value of TIL testing in different subtypes of breast cancer with at least one relevant outcome indicator was reported in the research or could be computed based on published data. (ii) The studies were of high quality and performed multivariate analysis on pathological complete response or survival data such as disease-free survival (DFS) or overall survival (OS). (iii) The hazard ratio (HR), odds ratio (OR) and their 95% confidence intervals (CIs) were reported or could be calculated according to the outcome data (DFS, OS or pCR). (iv) The samples were taken from core-needle biopsy specimens or surgical specimens after the operation
Summary
Whether tumour-infiltrating lymphocytes (TILs) play different roles in different molecular subtypes of breast cancer remains unknown. Their prognostic and predictive value in different molecular subtypes of breast cancer is still controversial. The complex interaction between the immune system and cancer cells plays a vital role in controlling and eradicating cancer and is regulated by a delicate balance between activation and suppression signals [3]. Research on the microenvironment of tumours can reveal the complex correlation between the immune system and the biological behaviour of cancer cells. Valuable information has been obtained, the heterogeneity in experimental design and TIL assessment has hindered a more comprehensive understanding of the biological value of TILs. the prognostic value of TIL remains complex and controversial. Breast cancer is a clinically and molecularly heterogeneous disease, and various factors determine the prognosis and response to treatment
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