Table 2.
Comparison of HER2 FISH Ratios and Average HER2 Gene Copy Numbers With HER2 Protein Expression by HercepTest IHC Scores in BCIRG Clinical Trials
| Overall Comparison of HER2 FISH Ratios and HER2 Copy Numbers With HER2 Protein by HercepTest IHC Scores | ||||||||
|---|---|---|---|---|---|---|---|---|
| PathVysion HER2 FISH Assay | HercepTest IHC Score* | Total | P† | ASCO-CAP FISH Group | ||||
| HER2 FISH Ratio | Average HER2 Copy Number per Cell | 0 | 1+ | 2+ | 3+ | |||
| < 2.0 | — | 2,098 (93.0%) | 137 (6.1%) | 19 (0.8%) | 3 (0.1%) | 2,257 (100%) | < .0001† | NA |
| 2.00-5.0 | — | 170 (35.4%) | 95 (19.8%) | 104 (21.6%) | 111 (23.1%) | 480 (100%) | NA | |
| 5.01-10.0 | — | 64 (6.7%) | 112 (11.7%) | 288 (30.1%) | 493 (51.5%) | 957 (100%) | NA | |
| > 10.0 | — | 30 (4.7%) | 65 (10.2%) | 181 (28.4%) | 361 (56.7%) | 637 (100%) | NA | |
| Total‡ | — | 2,362 | 409 | 592 | 968 | 4,331‡ | ||
| — | < 4.0 | 2,017 (93.6%) | 122 (5.7%) | 14 (0.6%) | 1 (0.05%) | 2,154 (100%) | < .0001† | NA |
| — | 4.01-6.0 | 166 (72.2%) | 44 (19.1%) | 17 (7.4%) | 3 (1.3%) | 230 (100%) | NA | |
| — | 6.01-8.0 | 48 (47.5%) | 23 (22.8%) | 19 (18.8%) | 11 (10.9%) | 101 (100%) | NA | |
| — | 8.01-10.0 | 25 (20.3%) | 27 (22.0%) | 34 (27.6%) | 37 (30.1%) | 123 (100%) | NA | |
| — | > 10.0 | 107 (6.2%) | 193 (11.2%) | 510 (29.5%) | 916 (53.1%) | 1,726 (100%) | NA | |
| Total‡ | 2,363 | 409 | 594 | 968 | 4,334‡ | |||
| Comparison of HER2 FISH Ratios and Copy Numbers With HER2 Protein by HercepTest Scores According to ASCO-CAP Groupings | ||||||||
| < 2.0 | < 4.0 | 1,988 (94.1%) | 114 (5.4%) | 10 (0.5%) | 1 (0.05%) | 2,113 (100%) | < .0001§ | Group 5 |
| ≥ 4.0-5.99 | 105 (78.4%) | 21 (15.7%) | 7 (5.2%) | 1 (0.7%) | 134 (100%) | < .0001§ | Group 4 | |
| ≥ 6.0 | 5 (55.6%) | 2 (22.2%) | 1 (11.1%) | 1 (11.1%) | 9 (100%) | .3881§ | Group 3 | |
| Total | 2,098 (93.0%) | 137 (6.1%) | 18 (0.8%) | 3 (0.1%) | 2,256 (100%) | < .0001§ | Groups 3-5 | |
| ≥ 2.0 | < 4.0 | 24 (68.6%) | 8 (22.9%) | 3 (8.6%) | 0 (0%) | 35 (100%) | < .0007‖ | Group 2 |
| ≥ 4.0-5.99 | 65 (65.7%) | 22 (22.2%) | 10 (10.1%) | 2 (2.0%) | 99 (100%) | < .0001‖ | Group 1 | |
| ≥ 6.0 | 175 (9.0%) | 242 (12.5%) | 561 (28.9%) | 963 (49.6%) | 1,941 (100%) | < .0001¶ | Group 1 | |
| Total | 264 (12.7%) | 272 (13.1%) | 574 (27.7%) | 965 (46.5%) | 2,075 (100%) | < .0001# | ||
| Total | 2,362 | 409 | 592 | 968 | 4,331 | |||
NOTE. Data from the BCIRG-007 trial comparing FISH with IHC are included in Table 2 but not in Table 3 of outcomes, because BCIRG-007 lacks a nontrastuzumab control arm.
Abbreviations: BCIRG, Breast Cancer International Research Group; CAP, College of American Pathologists; FISH, fluorescent in situ hybridization; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; NA, not applicable.
HercepTest scores were not available for 2,336 cases.
P value of Friedman test for increasing FISH ratio with increasing IHC.
The HER2 FISH ratio was not available for three cases.
P value of χ2 test for association between an HER2 FISH ratio < 2.0 and a lack of HER2 overexpression (ie, IHC0 and IHC1+).
P value of χ2 test for association between an HER2 FISH ratio ≥ 2.0, with either an average HER2 gene copy number < 4.0, or ≥ 4.0 but < 6.00, and a lack of HER2 overexpression (IHC0 and IHC1+).
P value of χ2 test for association between an HER2 FISH ratio ≥ 2.,0 with an average HER2 gene copy number ≥ 6.0, and HER2 overexpression (IHC3+).
P value of χ2 test for association between an HER2 FISH ratio ≥ 2.0 (without regard to average HER2 gene copy number/tumor cell nucleus) and HER2 protein overexpression (IHC3+).