Abstract 53P
Background
HER2-low is a novel breast cancer entity, however the ability of proper discrimination between HER2 negative and low is still matter of debate. This study investigates whether HER2 gene expression determined by ODX can differentiate between HER2 negative and low at IHC.
Methods
Retrospective cohort analysis on 229 patients with early BC tested with ODX after surgery in Humanitas Cancer Center between Jan 2020 and Jan 2023. We gathered well-known clinicopathological data, in particular HER2 by IHC, categorized as 0, 1+, and 2+ with negative fluorescent in situ hybridization (FISH). Difference between HER2 gene expression and HER IHC were tested with Wilcoxon test.
Results
In our cohort, 53.3% were HER2 0, 29.7% HER2 1+, and 17.0% HER2 2+. Clinical characteristics were similar in the three groups, including age and menopausal status without any statistical difference. The median recurrence score (RS) was 21 [IQR: 15-29], 20 (IQR: 15-31), and 21 (IQR: 15.5-28), respectively, for HER2 0, HER2 1+, and HER2 2+. RS > 25 was found in 42.6% of HER2 0 and 55.6% of HER2 2+ patients in the node-negative cohort, with no statistically significant difference (p = 0.618). In all patients, the median HER2 gene expression was 9.20 [IQR: 8.70- 9.60]. HER2 gene expression increased with the higher HER2 score at IHC with broad overlapping in three groups [HER2 0: median 8.90 (IQR 8.5 – 9.28); HER2 1+: median 9.40 (IQR 8.90 – 9.72); HER2 2+: median 9.50 (IQR 9.30 – 10.0)].
Table: 53P
HER2 gene expression and HER2 IHC by nodal status
| HER2 IHC | ||||
| Node negative | ||||
| 0 | 1+ | 2+ | p | |
| n | 54 | 29 | 18 | |
| Recurrence Score > 25 (%) | 23 (42.6) | 14 (48.3) | 10 (55.6) | 0.61 |
| Recurrence Score (median [IQR]) | 24.00 [17.25, 31.75] | 24.00 [17.00, 33.00] | 27.50 [20.25, 33.50] | 0.87 |
| HER2 gene expression (median [IQR]) | 8.90 [8.50, 9.28] | 9.20 [8.70, 9.70] | 9.50 [9.20, 9.78] | 0.001 |
| Node positive | ||||
| n | 68 | 39 | 21 | |
| Recurrence Score > 25 (%) | 18 (26.5) | 8 (20.5) | 4 (19.0) | 0.68 |
| Recurrence Score (median [IQR]) | 17.00 [13.75, 26.25] | 17.00 [14.00, 24.00] | 17.00 [13.00, 24.00] | 0.88 |
| HER2 gene expression (median [IQR]) | 8.90 [8.60, 9.22] | 9.50 [9.15, 9.90] | 9.60 [9.40, 10.10] | <0.001 |
Conclusions
HER2 gene expression was found to be increased by greater HER2 IHC but with significant overlap. This raises the possibility that subgroups with varying degrees of expression exist in all IHC categories which may be considered as a potential target for antibody-drug conjugates.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Zambelli: Non-Financial Interests, Personal, Invited Speaker, personal fees and non-financial support: Exact Science. All other authors have declared no conflicts of interest.