Reply to Clinical practice patterns and cost effectiveness of human epidermal growth receptor 2 testing strategies in breast cancer patients

In their recently published article, Phillips et al state that there is little information about HER-2 testing in clinical practice and suggest that testing is not being done in many cases. Unfortunately, almost none of the information in the paper is based on either current or peer reviewed data, and the conclusions provided, which the authors admit are based on old studies and reports that did not account for missing documentation, are inaccurate and potentially misleading. The statement that only 52% of breast cancer patients are tested is based on a study that addressed testing practices in 1999 and 2000. Although trastuzumab had only just been approved for patients with metastatic disease at the time of the study, Stark et al actually reported that HER-2 testing doubled by the end of 2000 (30.8% vs 69.2%). Although this indicates rapid adoption of testing once the drug was approved (and the percentage of patients tested is undoubtedly far higher now), the authors use those old data to conclude that many current breast cancers are untested. The paper states that as few as 32% of breast cancer patients have documentation of HER-2 testing, and that up to 20% of those receiving trastuzumab have not had a positive HER-2 test, but these statements are based solely on interviews with insurance industry sources and an abstract of an administrative claims review; not a single scientific paper is cited for these statements. The authors also suggest that patients who have negative test results may still receive trastuzumab because of physicians’ doubts about test accuracy or other factors, but provide no evidence to support this statement. Reporting these numbers as data is confusing. Finally, the authors claim that there is continuing debate over the cutoff used to determine an equivocal HER-2 test result, but this statement is no longer valid. The American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) HER-2 testing guidelines are now the standard of practice and have resulted in a high degree of consistency among labs in scoring both immunohistochemistry and fluorescent in situ hybridization tests. In a recent survey of a large number of laboratories doing HER-2 testing, 700 (97%) of 722 labs reported using standardized scoring criteria for reporting HER-2 results. The paper briefly discusses the accuracy of HER-2 assays, and we agree with the need for evidence-based guidelines that ensure testing is as accurate as possible. To meet these needs, CAP and ASCO have produced testing recommendations based on peer-reviewed, evidence based studies. ASCO has recommended HER-2 testing in all newly diagnosed breast cancer patients since 2000, and a newly revised Breast Cancer Protocol published by CAP in October 2009 requires HER-2 and hormone receptor testing and standardizes the reporting elements for these markers. The ASCO/CAP HER-2 testing guidelines include detailed specifications for assay validation, specimen handling, testing algorithms, scoring criteria, reporting, and proficiency testing. Compliance with the guideline is now a requirement for accreditation by CAP’s Laboratory Accreditation Program. Patients and physicians have every right to expect high-quality testing, but inaccurate and potentially misleading papers such as that published by Phillips et al are not helpful and will only lead to unnecessary anxiety among breast cancer patients.