Abstract
In August 2006, the Australian government approved subsidized trastuzumab therapy for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, and it was mandated that HER2 testing should be performed using in situ hybridization (ISH) rather than immunohistochemistry (IHC). Here we review results of the first regulated, nationwide program to provide HER2 ISH testing for all newly diagnosed breast cancer patients, with a particular emphasis on cases where IHC and ISH results were discordant. Data from all laboratories participating in the program were collated. Cases with an equivocal ISH test result [by chromogenic ISH (CISH) or silver ISH (SISH)] were tested centrally by fluorescence ISH. Most laboratories also performed HER2 IHC, and 200 cases with discordant IHC and ISH results were selected for further analysis in a central laboratory. A total of 26 laboratories were involved and 53,402 tests were reported. Over a 4-year period the HER2 positivity rate decreased for primary cancers from 23.8 to 14.6 %, but remained relatively constant for samples from metastases. Average ISH reporting times were <5 days for all yearly reporting periods. Test-repeat rates decreased for CISH (8.9–3.6 %) and SISH (13.7–8.4 %). Only 12 of 196 cases remained discordant after retesting in a central laboratory. These findings demonstrate the successful implementation of a regulated, national program that continues to collect data on HER2 status. The results also highlight the differences in IHC interpretation between local laboratories and a central, more experienced, laboratory. This model could be used to establish future biomarker-testing programs in other countries.
Highlights
The human epidermal growth factor receptor 2 (HER2) gene is amplified in *15–20 % of breast cancers and has been linked with poor prognosis [1,2,3,4,5,6], making it an attractive molecular target for breast cancer therapy.W
The HER2 positivity rate for early breast cancer (EBC) decreased each year from 23.8 % in the first 12-month period to 14.6 % in the final 12 months, whereas the metastatic breast cancer (MBC) HER2 positivity rate varied from 22.6 % in the first 12-month period to 25.1, 21.3, and 21.6 % in the second, third, and fourth 12-month periods, respectively
Results from states across Australia recorded over time HER2 human epidermal growth factor receptor 2, ISH in situ hybridization a Northern Territory cases were tested at an ISH reference laboratory in New South Wales
Summary
The human epidermal growth factor receptor 2 (HER2) gene is amplified in *15–20 % of breast cancers and has been linked with poor prognosis [1,2,3,4,5,6], making it an attractive molecular target for breast cancer therapy.W. Raymond Flinders Medical Centre, Bedford Park, Adelaide, SA 5042, Australia
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