Table 5.
Comparison of FISH Groups, FDA Guidelines Status, and ASCO-CAP Guidelines Status, and Associations With Outcomes in BCIRG Clinical Trials
| FISH | Group | Frequency, %* | FDA Status† | ASCO-CAP Guidelines | HER2 Protein Expression | Prognosis (BCIRG-005 trial) | Response to HER2-Targeted Therapy (BCIRG-006) | BCIRG/TRIO Study Conclusion | |
|---|---|---|---|---|---|---|---|---|---|
| Ratio | Average HER2 per Tumor Cell | ||||||||
| ≥ 2.0 | ≥ 4.0 | 1 | 40.8 | Amplified | ISH positive | HER2 overexpression (P < .0001; IHC3+) | Not included in trial | Significantly improved outcomes | HER2 amplified |
| ≥ 2.0 | < 4.0 | 2 | 0.7 | Amplified | ISH positive | HER2 low expression (P < .0001; IHC0/1+) | Not included in trial | No significant benefit | HER2 not amplified |
| < 2.0 | ≥ 6.0 | 3 | 0.5 | Not amplified | ISH positive | Combination of HER2 low and overexpression | Indeterminate mixed category | Indeterminate, mixed category | Mixed HER2 not amplified and amplified, on the basis of expression |
| < 2.0 | ≥ 4.0, < 6.0 | 4 | 4.1 | Not amplified | ISH equivocal | HER2 low expression (P < .0001; IHC0/1+) | Not associated with worse outcomes | Not included in trial | HER2 not amplified |
| < 2.0 | < 4.0 | 5 | 53.9 | Not amplified | ISH negative | HER2 low expression (P < .0001; IHC0/1+) | Not associated with worse outcomes | Not included in trial | HER2 not amplified |
Abbreviations: BCIRG, Breast Cancer International Research Group; CAP, College of American Pathologists; FDA, US Food and Drug Administration; FISH, fluorescent in situ hybridization; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; ISH, in situ hybridization; TRIO, Translational Research in Oncology.
*
Frequencies are based on screened population in Table 1.