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Randomized Controlled Trial
. 2012 Mar 15;14(2):R48.
doi: 10.1186/bcr3148.

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

Shuzhen Liu  1 , Jonathan Lachapelle, Samuel Leung, Dongxia Gao, William D Foulkes, Torsten O Nielsen
Affiliations
Randomized Controlled Trial

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

Shuzhen Liu et al. Breast Cancer Res. .

Abstract

Introduction: Tumor 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.

Methods: Immunohistochemistry 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.

Results: Among 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.

Conclusions: CD8+ 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.

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Figures

Figure 1
Figure 1
Breast cancer-specific survival (BCSS) by intratumoral tumor-infiltrating lymphocytes (iTILs) among groups with different age and estrogen receptor (ER) status. (a) Age of less than 50 years, (b) age of at least 50 years, (c) ER-, and (d) ER+. CI, confidence interval.
Figure 2
Figure 2
Breast cancer-specific survival (BCSS) by intratumoral tumor-infiltrating lymphocytes (iTILs) in different breast cancer intrinsic subgroups. (a) Luminal A, (b) luminal B, (c) HER2+/ER-, (d) triple-negative phenotype, (e) core basal phenotype, and (f) five negative phenotype subgroups. CI, confidence interval; ER, estrogen receptor; HER2, human epidermal growth factor receptor-2.
See this image and copyright information in PMC

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