HER-2/neu expression in primary and metastatic breast cancer

Breast Cancer Res Treat. 2009 Jan;113(2):301-6. doi: 10.1007/s10549-008-9931-6. Epub 2008 Feb 14.


Introduction Trastuzumab is a highly effective therapy for the treatment of HER-2/neu positive breast cancer. To maximize benefit and minimize unnecessary toxicity, patient selection is essential. Currently HER-2/neu analysis is routinely performed only for primary invasive breast cancers, and trastuzumab therapy is recommended based on primary analysis only. Methods Using immunohistochemistry, we performed a retrospective study comparing HER-2/neu expression in original primary to subsequent metastatic breast cancers. Results Tumors from 382 patients with metastatic breast cancer were studied. In 254 cases (66%) both primary and metastatic lesions were concordant. In 90 cases the primary lesion was HER-2/neu positive with the metastatic lesion negative; whereas, in 37 cases the primary lesion was HER-2/neu negative and the metastatic lesion positive. Primary HER-2/neu immunostaining was associated with a negative predictive value of 35.7%. Although all four groups were similar at diagnosis, survival differences were noted with the best survival experienced by patients with initial primary lesions HER-2/neu negative and subsequent metastatic lesions positive. Patients with hormone receptor and HER-2/neu positive primary lesions who received tamoxifen were more likely to have HER-2/neu positive metastasis. Conclusions The significant discordance between HER-2/neu expression in primary and metastatic tumors suggests that determination of HER-2/neu status in metastatic disease should be attempted.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Chemotherapy, Adjuvant
  • Cohort Studies
  • Female
  • Gene Amplification
  • Genes, erbB-2*
  • Humans
  • Middle Aged
  • Neoplasm Metastasis / drug therapy
  • Neoplasm Metastasis / genetics*
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / genetics
  • Predictive Value of Tests
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Receptor, ErbB-2 / analysis*
  • Survival Analysis
  • Tamoxifen / administration & dosage
  • Trastuzumab
  • Young Adult


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Neoplasm Proteins
  • Protein Kinase Inhibitors
  • Tamoxifen
  • Receptor, ErbB-2
  • Trastuzumab