Stability of HER-2/neu Expression Over Time and at Multiple Metastatic Sites

Niehans, Gloria A.; Singleton, Timothy P.; Dykoski, Daniel; Kiang, David T.

doi:10.1093/jnci/85.15.1230

Cited by 144 publications

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“…This result is in accordance with those concerning visceral metastases and local and regional metastases (Barnes et al, 1988;Niehans et al, 1993;Masood and Bui, 2000;Simon et al, 2001;Gancberg et al, 2002;Vincent-Salomon et al, 2002;Carlsson et al, 2004). Recently, in a meta-analysis of the published data concerning HER2 status stability among primaries and metastases, Carlsson et al (2004) confirmed that there was no drastic modification in HER2 status between primary tumours and their locoregional lymph node metastases and their distant visceral metastases.…”

Section: Discussionsupporting

confidence: 86%

“…HER2 status remains stable between the primary tumour site and distant metastasis (Niehans et al, 1993;Gancberg et al, 2002;VincentSalomon et al, 2002;Carlsson et al, 2004) or regional lymph node metastasis (Simon et al, 2001). In contrast, HER2 has been found to be overexpressed in 60 -100% in bone marrow micrometastatic cells, independently of the primary tumour status (Braun et al, 2001b).…”

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HER2 status of bone marrow micrometastasis and their corresponding primary tumours in a pilot study of 27 cases: a possible tool for anti-HER2 therapy management?

et al. 2007

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Discrepancies have been reported between HER2 status in primary breast cancer and micrometastatic cells in bone marrow. The aim of this study was to assess HER2 gene status in micrometastatic cells in bone marrow and corresponding primary tumour. Micrometastatic cells were detected in bone marrow aspirations in a prospective series of 27 breast cancer patients by immunocytochemistry (pancytokeratin antibody). HER2 status of micrometastatic cells was assessed by fluorescence in situ hybridisation (FISH), respectively in 24 out of 27. Primary tumour HER2 status was assessed by immunohistochemistry (CB11 antibody) and by FISH in 20 out of 27 of the cases. HER2 was amplified or overexpressed in five out of 27 (18.5%) primary tumours and in four out of 27 (15%) micrometastatic cells. In two cases, HER2 was overexpressed and amplified in primary tumour, but not in micrometastatic cells, whereas, in one case, HER2 presented a low amplification rate (six copies) in micrometastatic cells not found in the primary tumour. We demonstrated that negative and positive HER2 status remained, in the majority of the cases, stable between the bone marrow micrometastasis and the primary tumour. Therefore, the efficiency of anti-HER2 adjuvant therapy could be evaluated, in a clinical trial, by sequential detection of HER2-positive micrometastatic cells within the bone marrow, before and after treatment.

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Section: Discussionsupporting

confidence: 86%

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confidence: 99%

HER2 status of bone marrow micrometastasis and their corresponding primary tumours in a pilot study of 27 cases: a possible tool for anti-HER2 therapy management?

et al. 2007

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“…In most studies, concordance between primary tumour and distant metastases ranged between 87 and 100%. [32][33][34][35][36] Regitnig et al 13 found a newly occurring Her-2/neu amplification in metastases in 4 out of 18 cases (22%), 2 of which represented CNS metastases. In their series, Her-2/ neu-amplified primary tumours made up 14% of cases in the paired samples, which is different from our series consisting of brain-metastasizing tumours only.…”

Section: Discussionmentioning

confidence: 99%

Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer

et al. 2007

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Although breast cancer is the second most common cause of central nervous system (CNS) metastases with a notable increase of incidence, only few studies on brain-metastasizing breast cancer are available. In this immunohistochemical and fluorescence in situ hybridization (FISH) study, metastases to the CNS (n ¼ 85) and primary breast cancers, with known involvement of the CNS (n ¼ 44) including paired primary and metastasized tumours (n ¼ 23), were investigated retrospectively for the expression of oestrogen-(ER) and progesterone-(PR) hormone receptors, Her-2/neu, epidermal growth factor receptor (EGFR), Ki-67, and cytokeratins (CKs) 5/ 14. The majority of brain metastases were steroid hormone receptor negative (ER 66%, PR 82%) corresponding to the findings in primary tumours with known involvement of the CNS (68% ER-negative, 75% PR-negative). The frequency of HER-2/neu-overexpressing or -amplified cancers was increased in both groups (34 and 32%, respectively). EGFR expression was more frequent in metastases (41%) than in primary tumours (16%). The proportions of cases with a basal phenotype were 26 and 30%, respectively. In paired primary tumours and metastases to the CNS, constancy of Her-2/neu status was observed in 87% of cases with only one sample turning Her-2/neu-negative and two samples acquiring overexpression/amplification in brain metastases. In contrast, steroid hormone receptors exhibited more frequently a loss of expression (17%) than a gain (9%) with 74% revealing a constant phenotype. We conclude that brain-metastasizing breast cancer belongs predominantly to the basal type or Her-2/neu type. Primary and metastatic tumours differ from each other only in a minority of cases, leading rather to a loss of steroid hormone receptors and to a gain of EGFR and Her-2/neu.

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“…[2][3][4][5]23 For this last purpose, in the past 5 years the evaluation of HER-2 status was generally performed on the primary neoplasm, avoiding the biopsy of metastatic site, and in the assumption that the HER-2 status should remain stable in the years, as demonstrated in numerous previous studies, mostly based only on immunohistochemistry. [9][10][11]13,16,17 For this reason, to our knowledge, the necessity of HER-2 determination in metastatic lesion is not well established, at present time. 15 In this prospective study we have considered 119 pairs of primary tumours and their metastases subdivided in lymph node Cases with synchronous lymph node metastasis (group A), cases with metachronous lymph node metastasis (group B), cases with local recurrence (group C), cases with metachronous distant metastasis (group D).…”

Section: Discussionmentioning

confidence: 99%

“…Controversial opinions exist both about the stability of HER-2 status in breast carcinoma throughout the course of the disease, and about whether chemotherapy (neoadjuvant or adjuvant) can modify HER2 status. Most data have shown good overall concordance between primary and metastatic lesions, [9][10][11][12][13][14][15] but some data have demonstrated discordance in up to 20% of cases. 9,12,[16][17][18] These differences could be due to a possible genetic drift or clonal selection for HER-2, which may happen during tumour progression, 16 or to the presence of intratumoural heterogeneity of HER-2 status, [19][20][21] with a clone having enhanced metastatic potential, leading to metastases with different HER-2 status from that of the primary lesion.…”

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confidence: 99%

HER‐2 status discrepancy between primary breast cancer and metastatic sites. Impact on target therapy

Santinelli

Pisa

Stramazzotti

et al. 2007

Intl Journal of Cancer

134

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In this prospective study, we determined HER-2 status in primary breast invasive carcinomas and in the paired lymph node metastases (synchronous and metachronous), local recurrence and metachronous distant metastases, to verify the percentage of discordant cases. HercepTest TM and Fluorescence in situ hybridization (FISH) were used to determine HER-2 status on 119 cases of primary infiltrating breast carcinoma and paired metastases (45 cases with synchronous lymph node metastases, 9 cases with metachronous lymph node metastases, 30 cases with local recurrence, and 35 cases with metachronous distant metastases). A therapeutically significant HER-2 status discordance was demonstrated between primary carcinoma and synchronous lymph node metastases (6.7%), local recurrence (13.3%) and metachronous distant metastases (28.6%). In the first comparison, there was a normal HER-2 status in primary tumours and HER-2 amplification in paired metastases, in the second the opposite phenomenon was present, and both types of discordance were evident in the third comparison. Considering the cases of local recurrences and metachronous distant metastases all together, 14 out of 65 cases (21.5%) showed a therapeutically significant discordance of HER-2 status between the primary tumour and the paired metachronous recurrence or metastasis (p < 0.001), the 15.4% of cases showing normal HER-2 status in the primary tumour and HER-2 amplification in the neoplastic relapse. For the treatment of metastatic patients, the evaluation of HER-2 status should be performed in neoplastic tissue from metastatic site, whenever possible. This procedure could be also suggested in the patients that are metastatic at the time of diagnosis. ' 2007 Wiley-Liss, Inc.Key words: breast carcinoma; FISH; HER-2/neu; HercepTest TM ; metastasis The HER-2 proto-oncogene is located on chromosome 17q21 and encodes a transmembrane tyrosine kinase protein, which belongs to the epithelial growth factor receptors (EGFRs) family. Overexpression of the receptor or amplification of the HER-2 gene has been identified in 15-25% of invasive breast carcinomas and is very important both for the prognosis, 1 and for the therapy. 2,3 Trastuzumab is a humanized monoclonal antibody, which is used in the therapy of invasive breast carcinomas overexpressing HER-2 protein and/or showing HER-2 gene amplification. Trastuzumab treatment, in combination with chemotherapy, has given very good results, in terms of disease free survival and overall survival times, in patients with metastatic breast cancer 2 ; moreover, the results of recent trials on the efficacy of the drug in an adjuvant regimen have showed excellent results in terms of drastic reduction of the precocious relapses, when combined with chemotherapy. 4,5 Immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH) are the techniques recommended for HER-2 determination, according to the algorithm showed in Figure 1. Chromogenic in situ hybridization (CISH) has furnished promising results but is not yet considered an...

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Stability of HER-2/neu Expression Over Time and at Multiple Metastatic Sites

Abstract: The fact that p185 immunoreactivity is rarely heterogeneous is encouraging, both for the potential use of HER-2/neu-related proteins as serum tumor markers and for innovative therapies targeted at p185 expression.

Cited by 144 publications

References 0 publications

HER2 status of bone marrow micrometastasis and their corresponding primary tumours in a pilot study of 27 cases: a possible tool for anti-HER2 therapy management?

HER2 status of bone marrow micrometastasis and their corresponding primary tumours in a pilot study of 27 cases: a possible tool for anti-HER2 therapy management?

Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer

HER‐2 status discrepancy between primary breast cancer and metastatic sites. Impact on target therapy

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