CNS metastases of breast cancer show discordant immunohistochemical phenotype compared to primary

J Cancer Res Clin Oncol. 2013 Apr;139(4):551-6. doi: 10.1007/s00432-012-1358-0. Epub 2012 Dec 6.

Abstract

Purpose: A challenge in management of breast cancer is the development of brain metastases (BM). Because of improvements in systemic therapy with longer survival of patients with advanced cancer, BM can appear at a time when extra-BM disease is under control. Development of potential preventive strategies are considered, and new developments in systemic approaches to treatment of BM, (cytotoxic/targeted therapy), are explored. In primary breast cancer, ER/PR, HER2 are important biological markers for predicting prognosis and making effective treatment decisions. Known are changes in markers due to metastases, but clinical significance is still unclear. Aim of this retrospective study is to detect changes in immunohistochemical markers of primary and BM, to recognize concordance and impact on prognosis.

Methods: Twenty-one consecutive primary breast cancer patients who developed BM and got surgical resection of BM were enrolled in this study. Matched-pair analyses of primary and BM were done with evaluation by immunostaining (ER, PR, HER2).

Results: Loss of ER/PR receptor positivity was seen in BM compared to primary (ER: 47.6 %/9.0 %; PR: 42.9 %/0 %), respectively. High concordance exists for HER2 status in primary and BM (>80 %). HER2-positive breast cancer had a shorter median interval until appearance of metastases than HER2-negative patients (32.1/39 months; p = n.s.).

Conclusion: With loss of receptor positivity (ER/PR) in BM treatment, decisions are very difficult. High concordance of HER2 status was seen in matched-pair analysis. Further studies had to investigate whether HER3/4 is a possible target for further therapy.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / secondary*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology*
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / pathology*
  • Carcinoma, Medullary / metabolism
  • Carcinoma, Medullary / pathology*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasms, Second Primary / metabolism
  • Neoplasms, Second Primary / pathology*
  • Phenotype
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptor, ErbB-2