Diagnostic Performance of Techniques Used for HER-2 Testing in Breast Cancer

This report is a systematic review of the diagnostic performance of techniques used for HER-2 testing in breast cancer. The conclusions and recommendations may serve as a basis for the CEPO to develop clinical practice guidelines for testing and for the Direction de la lutte contre le cancer to organize services provided by pathology laboratories.

In 2007, an estimated 5900 women were diagnosed with breast cancer in Québec. Despite a decrease in the breast cancer mortality rate in all age groups, breast cancer remains the second leading cause of death from cancer in women and the leading cause of death among those under the age of 50. Approximately 1400 women died of breast cancer in 2007.

Given the clinical and economic impact of administering trastuzumab, a patient’s HER-2 status should be determined as accurately as possible, minimizing false-positive and false-negative results. To this end, there are several different diagnostic tests, each with its advantages and drawbacks. As well, the tests and utilization algorithms recommended by the various international organizations differ from country to country.

In light of these considerations, AETMIS recommends:

• that the authorities concerned implement an HER-2 testing quality assurance program in Québec and, as part of this program:

  • that at least one reference laboratory be designated;

  • that this or these reference laboratories develop and apply internal quality assurance measures;

  • that this or these laboratories’ results be periodically checked against those of other reference laboratories, provincial and Canadian or foreign;

  • that all laboratories that perform the tests in question be affi liated with a reference laboratory and be required to participate in the external quality assurance program to be established;

  • that the methods used by all the laboratories that perform the tests in question be validated initially and periodically and that these laboratories be required to meet the quality requirements set out by the reference laboratory or laboratories;

  • that the laboratories be required to meet the minimum number of cases to be tested annually recommended by Canadian standards, namely, 250 for IHC and 100 (ideally 200) for ISH tests, with a limit on the number of pathologists responsible for interpreting them, so as to maintain their expertise;

  • that the pathologists and the laboratory personnel involved receive ongoing training;

  • that the samples which hospitals are to submit to the laboratories that perform the tests in question be prepared in accordance with the best practices;

  • that the feasibility of setting up a central database containing the results of these tests and other relevant data for all patients with invasive breast cancer be assessed;

• that the Canadian recommendations concerning the use of IHC and FISH tests be followed by the laboratories, in particular, the use of IHC initially, followed by FISH (or other validated ISH tests) in cases of equivocal results;

• that FISH be the initial test performed when the quality of the sample received by the laboratory is questionable;

• that chromogenic in situ hybridization (CISH) be performed with two probes to confi rm an equivocal IHC result, one for the HER-2 gene, the other for the chromosome 17 centromere;

• that the diagnostic performance of silver-enhanced in situ hybridization be the subject of a literature watch until the evidence confi rms the validity of this technique.