HER2 expression in breast cancer primary tumours and corresponding metastases. Original data and literature review

Abstract

The aim of this study was to evaluate whether the HER2 expression in breast cancer is retained in metastases. The HER2 expression in primary tumours and the corresponding lymph node metastases were evaluated in parallel samples from 47 patients. The HercepTest was used for immunohistochemical analyses of HER2 overexpression in all cases. CISH/FISH was used for analysis of gene amplification in some cases. HER2 overexpression (HER2-scores 2 þ or 3 þ ) was found in 55% of both the primary tumours and of the lymph node metastases. There were only small changes in the HER2-scores; six from 1 þ to 0 and one from 3 þ to 2 þ when the metastases were compared to the corresponding primary tumours. However, there were no cases with drastic changes in HER2 expression between the primary tumours and the corresponding lymph node metastases. The literature was reviewed for similar investigations, and it is concluded that breast cancer lymph node metastases generally overexpress HER2 to the same extent as the corresponding primary tumours. This also seems to be the case when distant metastases are considered. It has been noted that not all patients with HER2 overexpression respond to HER2-targeted Trastuzumab treatment. The stability in HER2 expression is encouraging for efforts to develop complementary forms of therapy, for example, therapy with radionuclide-labelled Trastuzumab.

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?

“…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.…”

“…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.…”

“…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).…”

Efficacy of Primed In Situ Labelling in Determination of HER-2 Gene Amplification and CEN-17 Status in Breast Cancer Tissue

“…HER-2 oncogene is located on the long arm of chromosome 17 (17q12-q21) (Owens et al, 2004) and plays a role in the pathogenesis of a significant number of human tumours. Approximately 20-30% of breast carcinomas and probably a higher percentage in the more malignant subgroups that form lymph node or distant metastases show altered HER-2 expression (Eccles, 2002;Carlsson et al, 2004). This is manifested as gene amplification and/or protein overexpression (Ross and Fletcher, 1999).…”

HER-2/neu genotype of breast cancer may change in bone metastasis

“…11 Earlier studies exclusively used HercepTest to assess the maintenance of HER-2/neu genotype in metastatic lesions and found it concordant in case of lymph node, liver and lung metastases. [12][13][14][15][16] Recent reports provided evidence that the HER-2/neu genotype of BRC may change in the metastases: loss of HER-2/neu expression was reported in one case in pleural metastases, 17 while loss of HER-2/neu amplification was found in 21%, but appearance of HER-2/neu amplification was even more frequent in visceral metastases (30%). 18 Our aim was to analyze the HER-2/neu status of bone metastasis compared to the primary tumor in a larger cohort of BRC cases.…”