Breast Cancer With a HER2 FISH Group 2 Result: Should HER2 Tests be Repeated?

Area of Science:

• Oncology
• Pathology
• Genetics

Background:

• Historically, fluorescence in situ hybridization (FISH) group 2 breast cancer was considered HER2-positive.
• Updated 2018 guidelines classify this group as mostly HER2-negative unless immunohistochemistry (IHC) is 3+.
• The therapeutic relevance of HER2 FISH group 2 remains unclear.

Purpose of the Study:

• To assess if repeat HER2 testing (IHC and FISH) can aid in the final HER2 classification of breast cancer.
• To determine the therapeutic relevance of HER2 FISH group 2 in breast cancer patients.

Main Methods:

• Retrospective review of 23 breast cancer cases with HER2 FISH group 2 results from 2014-2018.
• Repeat HER2 tests were performed on available alternative tumor samples.
• Comparison of initial and repeat HER2 testing results based on 2018 ASCO/CAP guidelines.

Main Results:

• Only 1 of 23 cases (0.6%) was confirmed HER2-positive upon repeat testing.
• Among 13 primary tumors re-tested, 10 remained HER2-negative, while 3 converted from HER2-negative to HER2-positive.
• Three of 8 patients receiving anti-HER2 therapy achieved pathologic complete response (pCR), with 2 of these being HER2-positive converters.

Conclusions:

• HER2 FISH group 2 breast cancer may indicate heterogeneous tumor cell populations.
• Repeat HER2 testing on alternative samples can be valuable for guiding anti-HER2 therapy decisions.