A new update to clinical practice guidelines for HER2 testing in breast cancer was published online last week by the American Society of Clinical Oncology and the College of American Pathologists in the Journal of Clinical Oncology.
The guidelines recommend that all women with invasive breast cancer (primary or recurrence) are tested for HER2 status—a practice already being implemented across the United States. It also outlines details of sample preparation and HER2 testing, which can be carried out by two different platforms: immunohistochemistry to measure protein expression, or in situ hybridization to measure gene amplification.
Although for the majority of cases, testing will give a clear answer, showing either HER2-positive or HER2-negative status, approximately 5% of cases or less will test equivocal. In these cases, the test should be repeated, but using the other testing.
“It’s important to apply context,” says lead author Antonio Wolff, MD, professor of oncology at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, in an interview with Medscape. For example, if a tumor is low grade, measures of proliferation are low, and ER testing is positive, all of which might suggest a less aggressive tumor type, but if the HER2 test comes back positive, then he suggests a double-check. “I would want some reassurance from the pathologist on the test result.”
Dr. Wolff also suggested that it is worth retesting if the clinical course of the disease is surprising. For example, he hypothesized about a case in which other pathological features point to a low-grade tumor, and the HER2 test in the original primary tumor came back negative, but then the patient went on to develop lung and liver metastases, suggesting a different and aggressive phenotype. If possible at that point, it would be useful to biopsy a metastatic site for diagnostic confirmation and test the metastatic tumor.
Key Recommendations for Oncologists:
Must request HER2 testing on every primary invasive breast cancer (and on metastatic site, if stage IV and if specimen available) from a patient with breast cancer to guide decision to pursue HER2-targeted therapy. This should be especially considered for a patient who previously tested HER2 negative in a primary tumor and presents with disease recurrence with clinical behavior suggestive of HER2-positive or triple-negative disease.
Should recommend HER2-targeted therapy if HER2 test result is positive, if there is no apparent histopathologic discordance with HER2 testing, and if clinically appropriate. If the pathologist or oncologist observes an apparent histopathologic discordance after HER2 testing, the need for additional HER2 testing should be discussed.
Must delay decision to recommend HER2-targeted therapy if initial HER2 test result is equivocal. Reflex testing should be performed on the same specimen using the alternative test if initial HER2 test result is equivocal or on an alternative specimen.
Must not recommend HER2-targeted therapy if HER2 test result is negative and if there is no apparent histopathologic discordance with HER2 testing. If the pathologist or oncologist observes an apparent histopathologic discordance after HER2 testing, the need for additional HER2 testing should be discussed.
Should delay decision to recommend HER2-targeted therapy if HER2 status cannot be confirmed as positive or negative after separate HER2 tests (HER2 test result or results equivocal). The oncologist should confer with the pathologist regarding the need for additional HER2 testing on the same or another tumor specimen.
If the HER2 test result is ultimately deemed to be equivocal, even after reflex testing with an alternative assay (ie, if neither test is unequivocally positive), the oncologist may consider HER2-targeted therapy. The oncologist should also consider the feasibility of testing another tumor specimen to attempt to definitely establish the tumor HER2 status and guide therapeutic decisions. A clinical decision to ultimately consider HER2-targeted therapy in such cases should be individualized on the basis of patient status (co-morbidities, prognosis, and so on) and patient preferences after discussing available clinical evidence.
Source: Adapted from: Wolff, et al. Journal of Clinical Oncology.
Click here to view or download the full guideline PDF!