305P - Prognostic implications of HER2 changes after neoadjuvant chemotherapy in patients with HER2-zero and HER2-low breast cancer

Background

Transition of HER2 status after neoadjuvant chemotherapy (NAC) has frequently been reported previously; however, few study has focused on HER2-low breast cancer. Here, we evaluated the HER2 transition proportion among HER2-zero and HER2-low breast cancer cases post-NAC and the impact of clinical outcome after our initial report on pathologic complete response, long term outcomes and recurrence pattern in between two groups after neoadjuvant chemotherapy (S Kang, European Journal of Cancer, 2022).

Methods

We retrospectively reviewed HER2-zero and HER2-low breast cancer patients who underwent NAC and surgical resection during 2014–2018 at Asan Medical Center. We included 1288 patients who had paired pre- and post-therapeutic HER2 status results. HER2-zero was defined as immunohistochemistry (IHC)0, and HER2-low was defined as IHC1+ or IHC2+, with in situ hybridization-negativity.

Results

Of patients who were HER2-zero pre-NAC(n=650), 68% and 29% of patients were HER2-zero and HER2-low, respectively, post-NAC. Among patients who were HER2-low pre-NAC(n=638), 32% of patients showed HER2 changes, and 59% of patients had a constant HER2-low status post-NAC. Patients with constant HER2-low or transitions from HER2-low to zero had a higher proportion of hormone-receptor [HR] positivity (84% and 79%) than those with changes from HER2-zero to low (77%) or with constant HER2-zero (56%), respectively. Multivariable logistic regression analysis revealed that patients with HR positivity had a higher probability of gaining HER2-low expression than those with HR negativity (Odds ratio 2.48). No significant differences were observed in terms of overall survival and disease-free survival between patients with and without HER2-changes according to hormone receptor status, except in the post-therapeutic HER2-low HR-negative subset.

Conclusions

Temporal heterogeneity of HER2-low expression is observed in substantial portions of post-NAC breast cancer patients. Clinical outcomes show no significant associations, except in the post-therapeutic HER2-low, HR-negative subset. Prognostic implications of HER2 transition in HER2-low breast cancer require further investigation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

K.H. Jung: Non-Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Celgene, Eisai, Takeda, Novartis, Everest Medicine, Merck, Bixink. S. Kim: Non-Financial Interests, Institutional, Advisory Board: Lilly; Non-Financial Interests, Personal, Advisory Board: AstraZeneca, Daehwa Pharmaceutical, ISU Abxis, BeiGene, Daiichi Sankyo/AstraZeneca, OBI Pharma; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics, TC Corp, Genopeaks; Financial Interests, Personal, Other, Honoria: Daehwa Pharmaceutical, LegoChem Biosciences, Kalbe; Financial Interests, Institutional, Research Grant: Novartis, Dongkook Pharma, Genzyme. All other authors have declared no conflicts of interest.