Abstract 167P
Background
We aim to investigate the prognostic significance of HER2/CEP17 ratio, HER2 copy numbers, and tumor infiltrating lymphocytes (TILs) among early HER2+ breast cancer patients treated with HER2-targeted therapy.
Methods
In a retrospective cohort of 463 HER2+ breast cancer patients, 384 (82.9 %) were treated with the monoclonal antibody trastuzumab in an adjuvant setting and included in the study. HER2 re-testing (silver in situ hybridization and immunohistochemistry) was performed on whole tissue slides, along with stromal TIL scoring. The outcome endpoint was recurrence-free survival (RFS) with a median follow-up of 8.7 years. HER2 copy number, HER2/CEP17 ratio, and TILs were explored with positional scanning analysis (assessed by Cutoff Finder) to estimate prognostic cutoff levels. Survival analyses were carried out using Kaplan–Meier estimates and multivariable Cox regression models.
Results
The results showed that patients with high HER2 copy numbers had worse prognosis than patients with low HER2 copy numbers (RFS HR=2.2, CI 1.2-4.0, p=0.01). Similarly, a higher HER2/CEP17 ratio was associated with a worse prognosis as compared to a low ratio (RFS HR=3.3, CI 1.3-8.3, p=0.01). In addition, TILs showed robust prognostic potential (RFS HR=2.5, CI 1.1-6.0, p=0.04).
Conclusions
We concluded that both high HER2 copy numbers and high HER2 ratios were associated with worse outcomes than low levels among trastuzumab-treated HER2+ patients. TILs showed robust prognostic potential. Further studies, including molecular analyses, are needed to validate the findings and decipher the clinical implications to improve precision oncology in HER2+ breast cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Karolinska Institutet-Johan Hartman.
Funding
Cepheid AB and Roche.
Disclosure
S. Robertson: Other, Personal, Full or part-time Employment: Stratipath AB. T. Foukakis: Financial Interests, Institutional, Research Grant: Roche, Pfizer; Financial Interests, Personal, Advisory Board: Novartis, Affibody, Exact Sciences, Veracyte; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Institutional, Advisory Board: Roche, Pfizer; Other, Personal, Royalties: UpToDate. J. Hartman: Other, Personal, Advisory Board: Roche; Financial Interests, Institutional, Funding: Cepheid, Novartis, Roche; Financial Interests, Personal, Ownership Interest: Stratipath AB; Other, Personal, Speaker’s Bureau: Roche, Novartis, Pfizer, Eli Lilly, MSD, Veracyte, Exact Sciences. All other authors have declared no conflicts of interest.