2
Key Points
➤ Recommendations by the American Society of Clinical Oncology and
College of American Pathologists (ASCO/CAP) human epidermal
growth factor receptor 2 (HER2) Testing Expert Panel are aimed at
improving the analytic validity of HER2 testing and the clinical utility
of HER2 as a predictive biomarker for potential responsiveness to
therapies targeting the HER2 protein.
➤ HER2 gene amplification assessed by in situ hybridization (ISH) or
protein overexpression assessed by immunohistochemistry (IHC)
remains the primary predictors of responsiveness to HER2-targeted
therapies in breast cancer.
➤ Greater communication among health-care providers (especially
pathologists and oncologists) and appropriate infrastructure support
for specimen handling and laboratory facilities have led to observed
improvements in the analytic performance and accuracy of HER2 testing.
➤ All newly diagnosed patients with breast cancer must have a HER2
test performed. Patients who then develop metastatic disease must
have a HER2 test performed in a metastatic site, if tissue sample is
available.
➤ If a case has a HER2/CEP17 ratio is ≥2.0 but the average HER2
signals/cell is <4.0, a definitive diagnosis will be rendered based on
additional workup. (Strong Recommendation; EB-I)
• If not already assessed by the institution/lab performing the ISH test, IHC
testing for HER2 should be performed using sections from the same tissue sample
used for ISH and the slides from both ISH and IHC be reviewed together to
guide the selection of areas to score by ISH (local practice considerations will
dictate the best procedure to accomplish this concomitant assessment):
a. If the IHC result is 3+, diagnosis is HER2 POSITIVE
b. If the IHC result is 2+, recount ISH by having an additional observer, blinded
to previous ISH results, count at least 20 cells that include the area of invasive
cancer with IHC 2+:
▶ If reviewing the count by the additional observer changes the result
into another ISH category, the result should be adjudicated per internal
procedures to define the final category.
▶ If the count remains an average of <4.0 HER2 signals/cell and HER2/
CEP17 ratio ≥2.0, the diagnosis is HER2 NEGATIVE with a comment.*
c. If the IHC result is 0/1+, diagnosis is HER2 NEGATIVE with a comment.*
*Note: Refer to full text guideline for the specific comments associated with
each recommendation.
Highlights
