Comparison of HER-2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma.
BACKGROUND
Accurate assessment of HER-2 status is necessary prior to anti-HER-2 antibody (trastuzumab) therapy for metastatic breast carcinoma. However, controversy exists regarding whether to assess HER-2 status in the primary tumor or in metastatic lesions. It is also unclear whether HER-2 status can change during disease progression or after chemotherapy.


METHODS
Breast carcinoma samples from 60 women with known HER-2 status in both primary tumors and paired metastases (locoregional disease, n = 43 patients; distant disease, n = 17 patients) were reviewed retrospectively. Thirty-two patients underwent chemotherapy before their metastatic lesions were sampled, including 18 patients who received neoadjuvant chemotherapy and 14 patients who received adjuvant chemotherapy. The HER-2 gene was examined by fluorescence in situ hybridization either in paraffin-embedded tissue samples (48 primary tumors and 9 metastatic tumors) or in fine-needle aspirates (12 primary tumors and 51 metastatic tumors). HER-2 gene amplification was defined as a HER-2:chromosome 17 signal ratio >/= 2.0.


RESULTS
The HER-2 status of primary and metastatic tumors agreed in 58 of 60 patients (97%), including 18 (30%) amplified tumors and 40 (67%) nonamplified tumors. A discrepancy in HER-2 status was observed in specimens from two patients in which HER-2 amplification was detected in the primary tumor but not the metastatic tumors. In one patient, three foci of tumor nodules were found in the same breast; the HER-2 status was assessed in only one of them, which showed amplification; however, HER-2 amplification was not detected in the axillary lymph node metastasis. In another patient, the HER-2 gene was amplified in the primary tumor but not in the liver metastasis. No metastases showed HER-2 amplification without amplification in the primary tumor. Locoregional and distant metastases demonstrated similar concordance rates with their corresponding primary tumors (98% and 94%, respectively). Complete concordance of HER-2 status was found between primary tumors prior to chemotherapy and metastases that were sampled after chemotherapy.


CONCLUSIONS
The HER-2 status in breast carcinoma generally was stable during metastasis, whether to locoregional or distant sites. Chemotherapy did not modify the HER-2 status in metastatic lesions. Therefore, HER-2 amplification can be evaluated reliably in material from either primary or metastatic tumors in most patients. Further study with larger series is warranted to elucidate the significance of discordant results.
Gong
Yun
Y
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Booser
Daniel J
DJ
Sneige
Nour
N
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D016612:Paraffin Embedding; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases