Concordance of HER-2/neu expression of primary breast carcinomas and their metachronous distant metastases: results of a 10 year retrospective search in two university institutes of pathology

Lüftner, Diana; Dilk, H.; Henschke, P.; Geppert, R.; Dietel, Manfred; Stein, Harry M.; Wernecke, KD; Possinger, K.; Heine, Bernhard

doi:10.1016/s1359-6349(04)90766-5

Cited by 4 publications

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“…At the time of first diagnosis of metastatic disease, approximately 20% to 50% of patients have positive serum HER2 status [ 24 , 25 ]. Serum HER2 levels are correlated with HER2 tissue expression, suggesting that the frequency of HER2-positive metastases is higher than expected based on the reported frequency of HER2 positivity in primary tumors ranging from 15% to 30% [ 16 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Determination of HER2 status using both serum HER2 levels and circulating tumor cells in patients with recurrent breast cancer whose primary tumor was HER2 negative or of unknown HER2 status

et al. 2007

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Introduction At the time when metastatic disease is identified, assessment of human epidermal growth factor receptor (HER)2 status might help to optimize treatment decisions if HER2 status was not determined at first diagnosis and if HER2 positivity has been acquired during disease progression. Within this context, determination of serum HER2 or evaluation of HER2 status in circulating tumor cells (CTCs) may be of clinical relevance because metastatic tissue may be difficult to obtain for analysis as a result of its localization. The aim of this study was therefore to determine the HER2 status in serum and corresponding CTCs in patients with metastatic breast cancer whose primary tumors were HER2 negative or of unknown HER2 status.

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Section: Discussionmentioning

confidence: 99%

Determination of HER2 status using both serum HER2 levels and circulating tumor cells in patients with recurrent breast cancer whose primary tumor was HER2 negative or of unknown HER2 status

et al. 2007

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“…It was also reported that if all metastatic tumor sites were included in the analysis, then the HER-2/neu positive metastatic tumors with a corresponding negative primary tumor were more frequent than the converse, suggesting that HER-2/neu expression in primary tumors might represent an underestimation of reality. In another study [16], 80 paired primary tumors and metastatic tumors from the same patients were evaluated for HER-2/neu expression using tissue tests. A change from HER-2/neu negative status in the primary tumor to HER-2/neu positive status in the metastatic tumor occurred in 17% of cases.…”

Section: Comparison Of Her-2/neu Status: Primary Tumor Versus Metastamentioning

confidence: 99%

“…In more than 40% of the reports, it was found that 50% or more of the MBC patients had elevated serum HER-2/neu levels [16]. Several recent papers [18,51-53] reported that 50% to 60% of MBC patients had an elevated serum HER-2/neu.…”

Section: Frequency Of Elevated Serum Her-2/neu Levels In Breast Cancementioning

confidence: 99%

HER-2 therapy. HER-2/neu diagnostics in breast cancer

et al. 2007

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HER-2/neu status of the primary breast cancer (PBC) is determined by immunohistochemistry and fluorescent in situ hybridization. Because of a variety of technical factors, however, the PBC may not accurately reflect the metastatic tumor in terms of HER-2/neu status. Recently published guidelines recommend that tumors be defined as HER-2/neu positive if 30% or more of the cells are 3+. Circulating levels of the HER-2 extracellular domain can be measured in serum using a test cleared by the US Food and Drug Administration, and increased serum HER-2/neu levels to above 15 ng/ml can reflect tumor progression. Studies comparing tissue HER-2/neu status of the PBC and HER-2/neu levels above 15 ng/ml in metastatic breast cancer patients are also reviewed. IntroductionFor many years estrogen receptor (ER) status has guided the administration of hormone therapy to patients with breast cancer. Positive ER status narrows the pool of patients eligible for hormone therapy and increases the likelihood of favorable response. However, ER status indicates that approximately 50% of patients will respond, but it does not predict which patients will respond to hormone therapy. Similarly, the HER-2/neu status of breast carcinoma narrows the pool of candidates eligible for HER-2/neu directed therapies, but it does not definitively select those who will or will not respond.The HER-2/neu oncoprotein continues to be an important target in the development of a variety of new cancer therapies, which include mAb-based therapy, small-molecule drugs directed at the internal tyrosine kinase portion of the HER-2/ neu oncoprotein, and vaccines. The most widely known HER-2/ neu-directed therapy is trastuzumab (Herceptin; Genentech, South San Francisco, CA, USA). Trastuzumab is a humanized recombinant mAb that specifically targets the HER-2/neu extracellular domain (ECD). [6]. Therefore, accurate determination of the HER-2/neu status is extremely important in guiding therapy, and the reliability of the diagnostic method used to determine HER-2/neu status is critical in selecting the most appropriate patients for HER-2/neu directed therapies.The present review is focused on HER-2/neu testing, and so we address reports concerning the tissue tests used to determine HER-2/neu status as well as tests to quantitate circulating levels of the HER-2/neu ECD. Although there is approximately 80% to 85% accuracy in determining HER-2/ neu status by tissue analysis, studies collectively show that the HER-2/neu status of the primary breast cancer (PBC) does not always accurately reflect the HER-2/neu status of the MBC. We highlight some of the factors that contribute to inaccurate assessment of HER-2/neu status by tissue testing, in the hope that this will improve assessment of HER-2/neu status. We also review reports on assays that have been used to quantitate circulating levels of the HER-2/neu ECD, and we present evidence that not all HER-2/neu assays have been adequately validated, which has resulted in inaccurate Review HER2 therapy HER-2/neu dia...

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Re-Evaluation of HER2 Status in Metastatic Breast Cancer and Tumor-Marker Guided Therapy with Vinorelbine and Trastuzumab

Stemmler¹,

Stieber

Lässig

2005

Oncol Res Treat

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Background: HER2 is overexpressed in 20-30% of breast cancers. Compared to chemotherapy alone, chemotherapy with trastuzumab improves clinical outcome in patients with HER2-positive metastatic breast cancer (MBC). In general, HER2 status in a primary lesion predicts the status of metastases, so that biopsy of metastatic lesions appears unnecessary. Case Report: A 39-year old woman was diagnosed with primary breast cancer in November 2000. Using the method and scoring system of the DAKO Hercep Test, the tumor has shown low HER2 expression (DAKO score 1+). After failure of several chemotherapy regimens for metastatic disease (liver, skeletal), the patient underwent CT-guided needle biopsy of the liver which showed HER2 positive adenocarcinoma (DAKO score 3+). In consequence, the patient was treated with vinorelbine (30 mg/m2 d1,8,15 q4w) and trastuzumab (4 mg/kg loading dose, 2 mg/kg weekly). During a treatment period of 4 months imaging results as well as tumor marker kinetics indicated an excellent response with sustained decrease of tumor markers. A retrospective analysis of the HER2 shed antigen in metastatic stage revealed excessively increased serum levels and supports HER2 overexpression observed in liver metastasis. The kinetics of the HER2 shed antigen during therapy for metastatic disease were found to be in phase with the kinetics of CEA and CA15-3. Conclusion: This case report demonstrates that re-evaluation of the HER2 status may be helpful in single patients not sufficiently responding to treatment of metastatic disease. Determination of HER2 overexpression may be facilitated by a determination of the HER2 shed antigen level in peripheral blood.

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Concordance of HER-2/neu expression of primary breast carcinomas and their metachronous distant metastases: results of a 10 year retrospective search in two university institutes of pathology

Cited by 4 publications

References 0 publications

Determination of HER2 status using both serum HER2 levels and circulating tumor cells in patients with recurrent breast cancer whose primary tumor was HER2 negative or of unknown HER2 status

Determination of HER2 status using both serum HER2 levels and circulating tumor cells in patients with recurrent breast cancer whose primary tumor was HER2 negative or of unknown HER2 status

HER-2 therapy. HER-2/neu diagnostics in breast cancer

Re-Evaluation of HER2 Status in Metastatic Breast Cancer and Tumor-Marker Guided Therapy with Vinorelbine and Trastuzumab

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