Healthcare professionals involved in screening for the gene whose over-expression is linked with an aggressive form of breast cancer will now be wondering: what is in the new guideline? The answer comes quickly, in the “deck” that followed the headline: “Leading Health Care Organizations Recommend to Test All Patients with Invasive Breast Cancer for HER2 Status.”
The new guideline is important news for women in the United States who are challenged by breast cancer and for clinicians who treat people with the disease. It is also a landmark in personalized approaches to cancer and personalized medicine more generally. We are living in a time when that approach is changing from novelty to norm. More and more, the medical consumer expects it; certainly, the public is increasingly aware of it.
This is due, in part, to highly publicized cases of celebrities who made healthcare decisions partly on the basis of molecular diagnostics—most famously, actress Angelina Jolie, whose decision to undergo a preventive double mastectomy after discovering that she harbored the BRCA1 gene was widely reported. But it is also due, undoubtedly, to conversations between physicians and their patients that are occurring every day. Together, doctors and patients are getting a glimpse of the future of medicine. It is a future in which clinical laboratory professionals will play a central role.
The new guideline offers detailed recommendations for clinicians:
- Always test HER2 status on all newly diagnosed invasive breast cancers (primary site and/or metastatic site). Ensure that at least one tumor sample is tested for either HER2 protein expression (immunohistochemistry [IHC] assay) or (in situ hybridization [ISH assay]) for HER2 gene amplification.
- Discuss the role of HER2-targeted therapy if the HER2 test result is positive and if there is no apparent histopathologic discordance with HER2 testing.
- Delay the decision to recommend HER2-targeted therapy if the HER2 test result is equivocal. Mandatory retesting should be done on the same specimen using the alternative test if the initial HER2 test result is equivocal or on an alternative specimen.
- Do not administer HER2-targeted therapy if the HER2 test result is negative. If there is apparent histopathologic discordance with the HER2 test result, additional HER2 testing should be considered.
- Report a HER2 test result as indeterminate if technical issues prevent one or both tests (IHC and ISH) from being done in a tumor specimen, or prevent the test (or tests) from being reported as positive, negative, or equivocal.
- Confirm that the testing laboratory conforms to standards set for accreditation by CAP or an equivalent accreditation authority.
It is interesting that, in the release, the organizations directly address the issue of ambiguous results—as though trying to head off possible skepticism. Elizabeth
Hammond, MD, FCAP, co-chair of the ASCO/CAP HER2 Testing in Breast Cancer Panel, is quoted as follows: “The number of patients with equivocal HER2 test results used to be rather large. But evidence suggests that the quality of HER2 testing is improving and the frequency of equivocal and inaccurate results is decreasing. We believe that this is at least in part due to our earlier recommendations in 2007. We hope the current guideline will resolve remaining challenges in the field and ultimately result in better outcomes for all patients with breast cancer.”
For the clinical lab, the guideline means much possible new business, but it also raises an obvious issue: will such testing be covered by insurance providers, and by Medicare and Medicaid? With much uncertainty about reimbursement in these times, those questions need to be definitively answered.