Tumor-Infiltrating Lymphocytes/Plasmocytes in Chemotherapeutically Non-Influenced Triple-Negative Breast Cancers - Correlation with Morphological and Clinico-Pathological Parameters

Klin Onkol. 2019 Fall;32(5):380-387. doi: 10.14735/amko2019380.

Abstract

Background: Triple-negative breast cancers (TNBCs) are considered a morphologically heterogeneous group of breast carcinomas characterized by the absence or low protein expression of hormone receptors and HER2/neu/ERBB2 with a specific biological behavior and therapeutic response. This study aimed to evaluate correlations of the density of tumor-infiltrating lymphocytes/plasmocytes (TILs) in the tumor parenchyma, stroma, and invasive margins with tumor morphology, the proliferation rate, Bcl-2 expression, and selected clinical and pathological parameters in early breast cancer patients prior to mastectomy who had not received initial chemotherapy.

Materials and methods: Samples of 3,544 breast cancer patients investigated in our department between 2007 and 2017 were re-examined. In total, 413 (11.65%) patients were diagnosed with TNBC. Only 61 cases did not undergo neoadjuvant therapy prior to mastectomy. Correlations between the density of TILs and tumor morphology, Bcl-2 expression, proliferative activity measured by Ki-67, patient age at diagnosis, tumor grade, and metastases were investigated.

Results: The samples were predominantly relatively well-localized invasive carcinomas of no special type with medullary features (80.32%) that measured on average 13.4mm (range 5-20mm, median 15mm) and exhibited central necrosis or fibrosis, a tendency to undergo spindle cell and/or apocrine-like differentiation, and intensive infiltration of TILs. There were significant positive correlations between TILs and premenopausal status (p=0.003), Ki-67 expression (p=0.015), and tumor grade (p=0.002), a marginal positive correlation between TILs and tumor size (p=0.065), and a significant negative correlation between TILs and Bcl-2 expression (p=0.035). In younger patients (< 50 years) with tumor size less than or equal to 20 mm (pT1a-pT1c) we recorded a lower number of women with metastatic lymph node involvement (p=0.001).

Conclusion: The density and location of TILs in non-therapeutically influenced TNBCs, evaluated in the context of morphological changes and other clinicopathological parameters, may have prognostic significance and assist effective therapy planning.

Keywords: Bcl-2; clinico-pathological parameters; malignant neoplasm of breast; mastectomy; triple-negative breast neoplasms; tumor infiltrating lymphocytes; tumor morphology.

MeSH terms

  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Ki-67 Antigen / metabolism
  • Lymphocytes, Tumor-Infiltrating*
  • Mastectomy
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Grading
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Triple Negative Breast Neoplasms* / immunology
  • Triple Negative Breast Neoplasms* / metabolism
  • Triple Negative Breast Neoplasms* / pathology
  • Triple Negative Breast Neoplasms* / therapy

Substances

  • BCL2 protein, human
  • Ki-67 Antigen
  • MKI67 protein, human
  • Proto-Oncogene Proteins c-bcl-2