CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer

Abstract

IntroductionTumor infiltrating lymphocytes may indicate an immune response to cancer development, but their significance remains controversial in breast cancer. We conducted this study to assess CD8+ (cytotoxic T) lymphocyte infiltration in a large cohort of invasive early stage breast cancers, and to evaluate its prognostic effect in different breast cancer intrinsic subtypes.MethodsImmunohistochemistry for CD8 staining was performed on tissue microarrays from 3992 breast cancer patients. CD8+ tumor infiltrating lymphocytes were counted as intratumoral when in direct contact with tumor cells, and as stromal in adjacent locations. Kaplan-Meier functions and Cox proportional hazards regression models were applied to examine the associations between tumor infiltrating lymphocytes and breast cancer specific survival.ResultsAmong 3403 cases for which immunohistochemical results were obtained, CD8+ tumor infiltrating lymphocytes were identified in an intratumoral pattern in 32% and stromal pattern in 61% of the cases. In the whole cohort, the presence of intratumoral tumor-infiltrating lymphocytes was significantly correlated with young age, high grade, estrogen receptor negativity, human epidermal growth factor receptor-2 positivity and core basal intrinsic subtype, and was associated with superior breast cancer specific survival. Multivariate analysis indicated that the favorable prognostic effect of CD8+ tumor infiltrating lymphocytes was significant only in the core basal intrinsic subgroup (Hazard ratio, HR = 0.35, 95% CI = 0.23-0.54). No association with improved survival was present in those triple negative breast cancers that lack expression of basal markers (HR = 0.99, 95% CI = 0.48-2.04) nor in the other intrinsic subtypes.ConclusionsCD8+ tumor infiltrating lymphocytes are an independent prognostic factor associated with better patient survival in basal-like breast cancer, but not in non-basal triple negative breast cancers nor in other intrinsic molecular subtypes.

C‑reactive protein/albumin and neutrophil/lymphocyte ratios and their combination predict overall survival in patients with gastric cancer

“…As important components of the non-specific and adaptive immune response, lymphocytes are able to destroy tumor cells via cytotoxic cells and cytokine secretion (48). A decreased lymphocyte count results in reduced tumor resistance (49). These mechanisms support the results of the present study.…”

“…Of the available data, 42 (12.5%), 49 Association between CRP/Alb ratio, NLR and clinicopathological characteristics. The association between CRP/Alb ratio and NLR, and clinicopathological characteristics was assessed (Table I).…”

Comparison of basal-like triple-negative breast cancer defined by morphology, immunohistochemistry and transcriptional profiles

“…This is in contrast to some previous studies, showing that the expression of immunohistochemical basal markers correlates with a worse prognosis. 16 However, recently, 'Core Basal' lesions among triple-negative breast cancers with high CD8 þ infiltrating lymphocytes 28 and a Korean cohort 29 have also been reported to be associated with a better prognosis. These differences highlight the heterogeneity within triple-negative breast cancers, and the potential for identifying basal-like lesions with a good and a bad prognosis.…”

Towards tumor immunodiagnostics

“…CD8+ TILs have been associated with increased breast cancer specific survival in TNBC (74-76), HER2+ and ER+/HER2+ breast carcinomas (74) and in basal-like breast cancer but not in non-basal TNBC or in other intrinsic subtypes (77). CD8+ TILs have also been associated with response to adjuvant (74) and neoadjuvant anthracyclin+/− taxane-based chemotherapy (38).…”