Abstract
BackgroundTo 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.MethodsCitation 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.ResultsTwenty-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).ConclusionsThe elevation of TILs in breast tumors predicts favorable prognostic outcomes, particularly in the HER2-overexpression and TN subtypes.
Highlights
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 and to compare the presentation of high-level TILs across these molecular subtypes
Search strategy Electronic retrievals were performed from the PubMed, Web of Science, Cochrane Library and Embase databases according to the following search strategy: ((primary breast cancer) Odds ratio (OR) OR) AND ((tumor-infiltrating lymphocytes) OR OR OR OR) NOT
Search results After the systematic retrieval from the abovementioned databases, a total of 914 initial citations were obtained by using the search strategy, and 392 potential citations were left for title and abstract screening following the deletions of duplications (n = 285), conference papers (n = 219), reviews (n = 16) and case reports (n = 2)
Summary
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. The presentation of high-level TILs is positively associated with the survival benefits of anthracycline-based chemotherapy and anti-HER2 targeted therapy (trastuzumab) in HER2-positive breast tumors [5]. A pooled analysis of 3371 patients who underwent neoadjuvant therapy had a higher concentration of TILs, which led to a shorter overall survival (OS) than lower concentrations in the luminal phenotype of breast cancer, [6] suggesting a different biological feature of immune infiltration in this tumor subtype
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