title: Importance of confirming HER2 overexpression of recurrence lesion in breast cancer patients.
abstract: BACKGROUND
  The systemic management of metastatic breast cancer (MBC) is usually based on ER or HER2 status of the primary tumor. However, the hormonal status or the overexpression of human epidermal growth factor 2 (HER2) may change in every metastatic site because of the effects of the long-term treatment of metastatic cancer with endocrine therapy, chemotherapy, or biological agents. The purpose of this study was to investigate the frequency of change in HER2 expression in primary and distant metastatic tumors in breast cancer patients. Another objective of the study was to examine the effect of the clinical therapy on the basis of HER2 expression in a metastatic tumor.
  
  
  METHODS
  In our hospital between 1991 to December 2010, retrospectively, 156 patients had biopsy or surgical resection of their metastatic site. All sample were analyzed pathologically to confirm metastatic disease and, second, to evaluate HER2 status by immunohistochemistry or by FISH.
  
  
  RESULTS
  The recurrence lesions were resected from the breast or lymph node (n = 67, local lesion), brain (n = 27), lung (n = 16), liver (n = 20), bone (n = 16), and from the stomach, intestine, ovary, and uterus (n = 10). Loss, increase, or no change in HER2 overexpression was observed in 3, 5, and 92%, respectively. Positive changes of HER2 in metastatic sites were 3 (4%) local lesion, 3 (11%) brain, 1 (7%) lung, 0 (0%) liver, 2 (17%) bone, and 0 (0%) others. In 3 of these 8 patients, trastuzumab was administered. In 2 of 3 patients, trastuzumab achieved long stable disease. The negative conversion rate of HER2 expression in metastatic lesions was 37% in patients treated with trastuzumab and 6% in those not treated with trastuzumab, a significant difference between the two groups (P < 0.05).
  
  
  CONCLUSIONS
  The results of this study emphasize the significance of confirming HER2 expression in a recurrence lesion. For patients with positive conversion of HER2 status, more treatment options may be available. On the other hand, the rate of loss of HER2 expression was high in patients treated with trastuzumab, suggesting that the results of biopsy may provide an opportunity to reconsider treatment strategies for these patients.
authors.affiliation: Division of Breast Surgery, Chiba Cancer Center Hospital, 666-2 Nitona-Cho, Chuo-Ku, Chiba, Japan, rikiya@graduate.chiba-u.jp.
authors.forename: Rikiya
authors.initials: R
authors.lastname: Nakamura
authors.forename: Naohito
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Onai
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Hidetada
authors.initials: H
authors.lastname: Kawana
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human