10
Optimal Algorithm
Figure 4. Clinical Question 3 "Group 2"
HER2/CEP17 ratio ≥2.0
Average HER2 signals/cell <4.0
Assess IHC using sections from the
same tissue sample used for ISH
IHC 0/1+
HER2/CEP17 ratio
≥2.0
Average HER2
signals/cell <4.0
IHC 3+
HER2 Negative
with Comment
a
a
Comment: Evidence is limited on the efficacy of HER2-targeted therapy in the small subset of cases
with HER2/CEP17 ratio ≥2.0 and an average HER2 copy number <4.0/cell. In the first generation
of adjuvant trastuzumab trials, patients in this subgroup who were randomized to the trastuzumab
arm did not appear to derive an improvement in disease free or overall survival, but there were
too few such cases to draw definitive conclusions. IHC expression for HER2 should be used to
complement ISH and define HER2 status. If IHC result is not 3+positive, it is recommended that
the specimen be considered HER2 negative because of the low HER2 copy number by ISH and lack
of protein over expression.
Other ISH Result
Observer blinded to previous
results recounts ISH,
counting at least 20 cells
Result should be
adjudicated per
internal procedures
to determine final
category
IHC 2+
HER2 Positive
HER2
Negative with
Comment
a
