Defining lymphocyte-predominant breast cancer by the proportion of lymphocyte-rich stroma and its significance in routine histopathological diagnosis

Pathol Int. 2015 Dec;65(12):644-51. doi: 10.1111/pin.12355. Epub 2015 Nov 4.

Abstract

Lymphocyte-predominant breast cancer (LPBC) defined by the density of stromal lymphocytes shows favorable behavior. However, considerable distribution heterogeneity of lymphocytes is a major problem. The present study defined LPBC by the proportion of lymphocyte-rich stroma with the cut-off values of 30, 50, and 75%, and clinicopathologically analyzed mainly LPBC (area > 30%) defined by the cut-off value of 30%. LPBCs (area > 30%), 39 cases in total, were composed mainly of triple-negative and HER2(+) /ER(-) subtypes, without any luminal A-like subtype. LPBCs were composed predominantly of histological grade 3 tumors, without any grade 1 lesions. Multivariate analyses on 477 consecutive tumors revealed that ER-negativity and grade 3 status associated significantly with LPBC. LPBC (area > 30%) showed better disease-free survival than grade-matched controls, and it was a good indicator of complete pathological remission after pre-operative chemotherapy. Patients with LPBC with the cut-off value of 50% and that of 75% showed 100% disease-free survival. These results demonstrated the validity of our definition of LPBC. Our data also suggest that de-differentiated cancers without TILs could be regarded as high-grade cancer without lymphocyte-mediated responses. In conclusion, the definition of LPBC by the proportion of lymphoid stroma is useful for prognostication of high grade breast cancer in routine diagnosis.

Keywords: anti-tumor immunity; invasive breast cancer; lymphocyte-predominant breast cancer; tumor-infiltrating lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / classification*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Dedifferentiation
  • Disease-Free Survival
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Middle Aged
  • Neoplasm Grading
  • Prognosis
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism
  • Stromal Cells / pathology

Substances

  • Receptors, Estrogen
  • ERBB2 protein, human
  • Receptor, ErbB-2