Stability of HER2-positive status in breast carcinoma: a comparison between primary and paired metastatic tumors with regard to the possible impact of intervening trastuzumab treatment.
BACKGROUND
To date, the stability of human epidermal growth factor receptor 2 (HER2)-positive primary breast carcinomas during disease progression and the role of intervening trastuzumab treatment in the loss of HER2-positive status in paired metastases remain under-investigated.


METHODS
Sixty-six patients with HER2-positive primary carcinoma and paired metastasis were evaluated. We examined the overall agreement of the HER2 status and compared the status agreement between 38 trastuzumab-treated patients and 28 trastuzumab-naive control patients. The impact of chemotherapy, endocrine therapy, metastatic site (locoregional or distant), and time to relapse (≥5 or <5 years) on the HER2 status change was assessed.


RESULTS
Fifty-six (84.9%) patients had HER2 status agreement between paired tumors; 10 patients had HER2-positive-to-negative conversion. The agreement rate in the trastuzumab-treated group and in the control group was comparable (86.8% versus 82.1%) (P = 0.858). Chemotherapy, endocrine therapy, metastatic site, and time to relapse did not significantly affect HER2 stability in either group. In the discordant tumor pairs, variations in testing methods and borderline scores were common.


CONCLUSIONS
HER2-positive status remained unchanged in most paired metastases. Loss of HER2-positive status did not seem to be affected by trastuzumab treatment. Differences in testing and interpretation may account for the discordance in some cases.
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Breast Oncology, Tianjin Medical University Cancer Hospital, Tianjin, China.
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Xiao
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: yungong@mdanderson.org.
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Gong
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
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EY
Han
Departments of Breast Medical Oncology; Department of System Biology, The University of Texas MD Anderson Cancer Center, Houston, USA.
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Gonzalez-Angulo
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
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Sneige
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D000068878:Trastuzumab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human