Elevated serum c-erbB-2 antigen levels and decreased response to hormone therapy of breast cancer.

Leitzel, Kim; Teramoto, Y A; Konrad, Kristine; Chinchilli, Vernon M.; Volas, Gena H.; Grossberg, Howard; Harvey, Harold A.; Demers, Laurence M.; Lipton, Allan

doi:10.1200/jco.1995.13.5.1129

Cited by 256 publications

(121 citation statements)

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“…5,6 Response to some types of chemotherapy and hormonal therapy also appears to be dependent on HER2 status. [9][10][11][12][13][14] Results of this study show CISH to be a practical and reliable alternative to FISH for the assessment of HER2 gene amplification in breast cancer specimens. A very high level of concordance was seen between CISH and FISH in each of the tumor sample groups tested.…”

Section: Discussionmentioning

confidence: 99%

Chromogenic in-situ hybridization: a viable alternative to fluorescence in-situ hybridization in the HER2 testing algorithm

Hanna

Kwok

2006

Modern Pathology

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Assessment of human epidermal growth factor receptor-2 status is standard practice in women with breast cancer. Most laboratories use immunohistochemistry as a screening test, with equivocal results confirmed by fluorescence in-situ hybridization (FISH). Chromogenic in-situ hybridization (CISH) is a relatively new method for detection of gene amplification using a peroxidase reaction, which can be viewed using a standard light microscope. This study was undertaken to validate CISH as a method for assessing human epidermal growth factor receptor-2 gene amplification. The gene amplification status of human epidermal growth factor receptor-2 immunohistochemistry negative (0/1 þ , n ¼ 69; Group 1), immunohistochemistry positive (3 þ , n ¼ 50; Group 2) and equivocal tumor samples (2 þ , n ¼ 135; Group 3) was evaluated by FISH and CISH, and the concordance between FISH and CISH results calculated. In Group 1, 67/69 cases did not show amplification by CISH and 69/ 69 showed no amplification by FISH. Two cases were discordant; therefore, fluorescence/CISH concordance was 97%. In Group 2, 46/50 cases were amplified by FISH and 47/50 cases were amplified by CISH; three cases were not amplified by either method (immunohistochemistry false-positives). Only one case showed discordant FISH and CISH results, making the fluorescence/CISH concordance 98%. In Group 3, 89/135 cases were not amplified and 37/135 were amplified by both methods. Nine cases were discordant, giving a fluorescence/CISH concordance of 93%. The discordant cases were those with very low or borderline amplification with FISH. The high level of concordance between FISH and CISH seen in this study suggests that CISH may be a viable alternative to FISH for use in the human epidermal growth factor receptor-2 testing algorithm.

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Section: Discussionmentioning

confidence: 99%

Chromogenic in-situ hybridization: a viable alternative to fluorescence in-situ hybridization in the HER2 testing algorithm

Hanna

Kwok

2006

Modern Pathology

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“…[14][15][16][17][18][19] Overexpression correlates with an increased tumour burden and reduced survival. [14][15][16]18,[22][23][24][25] Since EIA (enzyme immunoassay) is a relatively simple assay commonly used in clinical medicine, the possibility that elevated levels of extracellular HER-2 could indicate poor prognosis in patients with MBC is of particular interest.…”

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confidence: 99%

Expression of C-erbB-2/HER-2 in patients with metastatic breast cancer undergoing high-dose chemotherapy and autologous blood stem cell support

Bewick

Chadderton

Conlon

et al. 1999

Bone Marrow Transplant

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Summary:C-erbB-2/HER-2 (designated HER-2) is overexpressed in both primary and metastatic breast cancer and predicts poor prognosis. We investigated the expression of HER-2 in patients with metastatic breast cancer undergoing high-dose chemotherapy (HDCT) with autologous blood stem cell (ABSC) support and correlated the presence (positive) or absence (negative) of HER-2 overexpression in these patients with response to treatment, progression-free survival (PFS) and overall survival (OS). The level of HER-2 expression was analyzed in 57 patients with metastatic breast cancer undergoing HDCT with ABSC support. Plasma from peripheral blood was taken at three different time points during the course of treatment and was analyzed using an enzyme immunoassay (EIA) to detect circulating levels of the extracellular portion of HER-2. HER-2 levels were elevated (Ͼ0.2 U/mg protein) in 27/57 (47.4%) patients at one or more time points during treatment. The level of HER-2 varied during the course of treatment. Following induction chemotherapy (ICT), five patients who were negative initially, showed overexpression of HER-2. Three patients overexpressed HER-2 only after HDCT/ABSC. Response to treatment was similar in patients independent of plasma HER-2 levels. Overexpression of HER-2 was associated with a significantly shorter PFS (P = 0.004, log rank) and OS (P = 0.003, log rank) after HDCT/ABSC. HER-2 overexpression, patient age, estrogen receptor status, progesterone receptor status, and previous hormone treatment were assessed by univariate and multivariate analysis. Univariate analysis determined that only HER-2 overexpression correlated significantly with decreases in progression free survival (P = 0.005, Cox regression). Decreased overall survival correlated significantly with HER-2 overexpression (P = 0.004) and decreased expression of both estrogen receptor (P = 0.032) and progesterone receptor (P = 0.039). In multivariate analysis of these variables, only HER-2 expression levels proved to be of independent statistical significance in predicting outcome for both PFS (P = 0.007) and OS Correspondence: Dr S Glück, Depts Oncology, Medicine, and Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Tom Baker Cancer Centre, 1331, 29th Street NW, Calgary, Alberta, Canada Received 18 August 1998; accepted 5 May 1999 (P = 0.002). These results suggest that overexpression of HER-2, measured by EIA in plasma may predict a shorter PFS and OS in patients with metastatic breast cancer treated with HDCT and ABSC support.

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“…Amplification of the HER-2 gene or overexpression of the HER-2 protein has been identified in 10 -34% of primary breast carcinomas and is associated with adverse clinical outcomes and drug resistance in patients with breast carcinoma. [1][2][3][4] Trastuzumab is a high-affinity, humanized, anti-HER-2 antibody for the treatment of advanced breast carcinoma, especially metastasis, 5,6 and its efficacy is associated directly with the HER-2 status of the tumor. 5,7 Although therapy targets metastases, to our knowledge there is no agreement on whether HER-2 status should be assessed in primary tumors or metastases, because controversy exists among previous studies regarding the stability of HER-2 status in breast carcinoma throughout the course of the disease.…”

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confidence: 99%

Comparison of HER‐2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma

Gong

Booser

Sneige

2005

Cancer

144

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BACKGROUNDAccurate 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.METHODSBreast 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.RESULTSThe 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.CONCLUSIONSThe 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. Cancer 2005. © 2005 American Cancer Society.

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Elevated serum c-erbB-2 antigen levels and decreased response to hormone therapy of breast cancer.

Abstract: Patients with ER+/c-erbB-2+ metastatic breast cancer are less likely to respond to hormone treatment than ER+/c-erbB-2- patients. Their survival duration is also shorter.

Cited by 256 publications

References 25 publications

Chromogenic in-situ hybridization: a viable alternative to fluorescence in-situ hybridization in the HER2 testing algorithm

Chromogenic in-situ hybridization: a viable alternative to fluorescence in-situ hybridization in the HER2 testing algorithm

Expression of C-erbB-2/HER-2 in patients with metastatic breast cancer undergoing high-dose chemotherapy and autologous blood stem cell support

Comparison of HER‐2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma

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