212P - HER2-low breast cancer: Evolution from primary tumor to residual disease after neoadjuvant treatment

Background

Approximately a half of breast tumors traditionally classified as HER2-neg exhibit HER2-low expression (IHC 1+ or 2+ and ISH neg.). We recently described a high instability of HER2-low expression from primary breast cancer (BC) to relapse (Miglietta F et al., ESMO Breast Cancer 2021). Aim of this study is to track the evolution of HER2-low expression from primary BC to residual disease (RD) after neoadjuvant treatment.

Methods

Patients undergoing neoadjuvant treatment with available baseline tumor tissue and matched samples of RD (in case of no pCR) were included. HER2 expression was evaluated according to ASCO/CAP recommendations in place at the time of diagnosis. Cases diagnosed between 2007 and 2013 were reviewed to comply with the 10% cutoff of IHC for HER2-positivity. HER2-neg cases were further classified as HER2-0 or HER2-low (IHC 1+ or 2+ and ISH neg.).

Results

447 patients were included. Primary BC phenotype was: HR-pos/HER2-neg 23%, triple-negative (TN) 35%, HER2-pos 42%. HER2-low cases were 56% of the HER2-neg cohort and were significantly enriched in the HR-pos/HER2-neg vs TN subgroup (69% vs 47%, p=0.001). In patients failing to achieve pCR after neoadjuvant treatment (n=292), the overall rate of HER2 expression discordance was 27%, mostly driven by cases converting either from HER2-0 primary BC to HER2-low RD (9%) or from HER2-low primary BC to HER2-0 RD (15%; Table). Overall, 36% of non-pCR patients had a HER2-low expression on RD, including 12% of patients with TN and 24% of patients with HR-pos/HER2-neg disease. Among HR-pos/HER2-neg patients with HER2-low expression on RD, 23% had an estimated high risk of relapse according to the residual proliferative cancer burden (RPCB class 3). Table: 212P

Conclusions

HER2-low expression showed high instability from primary BC to RD after neoadjuvant treatment. HER2-low expression on RD may guide personalized adjuvant treatment for high-risk patients in the context of clinical trials with novel anti-HER2 antibody-drug conjugates.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

DOR funding from the University of Padua – Department of Surgery, Oncology and Gastroenterology: BIRD 2019 and BIRD 2020.

Disclosure

G. Griguolo: Financial Interests, Personal, Other, Travel grant: Pfizer; Financial Interests, Personal, Other, Travel grant: Novartis; Financial Interests, Personal, Other, Travel grant: Amgen. M. Fassan: Financial Interests, Institutional, Research Grant, outside the submitted work: Astellas Pharma; Financial Interests, Institutional, Research Grant, outside the submitted work: QED Therapeutics; Financial Interests, Personal, Advisory Board, outside the submitted work: Diaceutics; Financial Interests, Personal, Advisory Board, outside the submitted work: Tesaro; Financial Interests, Personal, Advisory Board, outside the submitted work: Astellas Pharma; Financial Interests, Personal, Advisory Board, outside the submitted work: Roche. P.F. Conte: Financial Interests, Personal, Advisory Board, outside the submitted work: Novartis; Financial Interests, Personal, Advisory Board, outside the submitted work: Eli Lilly; Financial Interests, Personal, Advisory Board, outside the submitted work: AstraZeneca; Financial Interests, Personal, Advisory Board, outside the submitted work: Tesaro; Financial Interests, Personal, Other, honoraria outside the submitted work: BMS; Financial Interests, Personal, Other, honoraria outside the submitted work: Roche; Financial Interests, Personal, Other, honoraria outside the submitted work: EliLilly; Financial Interests, Institutional, Research Grant, outside the submitted work: Novartis; Financial Interests, Institutional, Research Grant, outside the submitted work: Roche; Financial Interests, Institutional, Research Grant, outside the submitted work: BMS; Financial Interests, Institutional, Research Grant, outside the submitted work: Merck-KGa; Financial Interests, Institutional, Research Grant, outside the submitted work: Italian Ministry of Health; Financial Interests, Institutional, Research Grant, outside the submitted work: Veneto Secretary of Health; Financial Interests, Institutional, Research Grant, outside the submitted work: University of Padua. V. Guarneri: Financial Interests, Personal, Invited Speaker, outside the submitted work: EliLilly; Financial Interests, Personal, Advisory Board, outside the submitted work: Eli Lilly; Financial Interests, Personal, Advisory Board, outside the submitted work: MSD; Financial Interests, Personal, Advisory Board, outside the submitted work: Novartis; Financial Interests, Personal, Invited Speaker, outside the submitted work: Novartis; Financial Interests, Personal, Advisory Board, outside the submitted work: Roche; Financial Interests, Institutional, Principal Investigator, outside the submitted work: AstraZeneca; Financial Interests, Institutional, Principal Investigator, outside the submitted work: BMS; Financial Interests, Institutional, Principal Investigator, outside the submitted work: Eli Lilly; Financial Interests, Institutional, Principal Investigator, outside the submitted work: MSD; Financial Interests, Institutional, Principal Investigator, outside the submitted work: Novartis; Financial Interests, Institutional, Principal Investigator, outside the submitted work: Roche; Financial Interests, Institutional, Principal Investigator, outside the submitted work: Synton Biopharmaceuticals. M.V. Dieci: Financial Interests, Personal, Advisory Board, outside the submitted work: Eli Lilly; Financial Interests, Personal, Advisory Board, outside the submitted work: Genomic Health; Financial Interests, Personal, Advisory Board, outside the submitted work: Novartis; Financial Interests, Personal, Advisory Board, outside the submitted work: Celgene. All other authors have declared no conflicts of interest.