Abstract 10P
Background
HER2 loss on residual disease (RD) is frequent after NAT. Subtype switch has been also reported, with HER2-Enriched (HER2E) tumors converting frequently to non-HER2E. However, the association between HER2 immunohistochemistry (IHC) status and intrinsic subtype (IS) has never been described.
Methods
Between Feb/08 and Mar/22, 82 patients (pts) with HER2+ BC who underwent NAT at Hospital Clinic of Barcelona and had RD with matched IHC data were included. HER2 loss was defined as HER2 IHC 0/1+ or 2+/ISH not amplified on RD. Research-based PAM50 subtyping was performed with the nCounter platform. Associations between HER2 loss, IS dynamics, clinicopathological characteristics and event-free survival (EFS) were assessed.
Results
At baseline, 61% (n=50) of tumors were HER2 3+ and 83% (n=68) were hormone receptor (HR) positive. All pts received NAT with trastuzumab, 98% with chemotherapy, 52% with pertuzumab; and 24% received adjuvant T-DM1. HER2 loss was identified in 46% of BC (24 IHC 0, 12 IHC 1+, 2 IHC 2+/ISH-). IS was assessed on 73 baseline and 72 RD samples (67 paired). Distribution of IS at baseline was: HER2E 42%, LumA 31%, LumB 14%, normal-like 9%, basal-like 4%; on RD was: HER2E 17%, LumA 36%, LumB 8%, normal-like 33%, basal-like 5%. ERBB2 mRNA levels significantly decreased after NAT (p=0.001). An IS switch was observed in 40% (n=27) of samples and was not associated with HER2 loss (p=0.455). However, HER2 loss was numerically more frequent among BC that switched from HER2E to non-HER2E (58%) than in BC that remained HER2E (23%) (p=0.082). In a multivariate regression analysis including baseline IHC, ERBB2 mRNA, IS, HR status, time from NAT to surgery and administration of dual HER2 blockade, only ERBB2 mRNA was significantly associated with HER2 loss (p=0.003). At a median follow up of 61.0 months, 12 EFS events were recorded. After adjusting for T-DM1 use, none of the variables assessed, including HER2 loss, was associated with EFS.
Conclusions
HER2 loss was associated with decrease in ERBB2 mRNA levels, was more frequent in tumors switching from HER2E to non-HER2E subtype, and was not associated with EFS. Further validation on large cohorts is warranted.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
F. Brasó-Maristany: Financial Interests, Personal, Invited Speaker: Reveal Genomics. T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer/ AstraZeneca / Veracyte / Novartis; Financial Interests, Personal, Advisory Board: Roche/Genentech. F. Schettini: Financial Interests, Personal, Invited Speaker: Novartis, Gilead, Daiichi Sankyo; Financial Interests, Personal, Other, Travel expenses: Novartis, Gilead. M.J. Vidal Losada: Financial Interests, Personal, Advisory Board: Novartis/Pfizer, Roche, Pfizer, AstraZeneca/Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Novartis/Pfizer, Roche/Genentech, AstraZeneca/Daiichi Sankyo, Gilead Sciences; Financial Interests, Personal, Other, Travel, Accommodations, expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Gilead Sciences. M. Munoz: Financial Interests, Personal, Expert Testimony: Roche, Novartis; Financial Interests, Personal, Other, International conference travel grants: Roche, Pfizer, Lilly, Gilead; Financial Interests, Personal, Advisory Board: Pierre Fabre, Seagen, AstraZeneca. N. Lin: Financial Interests, Institutional, Sponsor/Funding: Genentech, Pfizer, Merck, Seattle Genetics, Zion Pharmaceuticals, Olema Pharmaceuticals, AstraZeneca; Financial Interests, Personal, Other, Consulting honoraria: Puma, Seattle Genetics, Daiichi Sankyo, AstraZeneca, Denali Therapeutics, Prelude Therapeutics, Olema Pharmaceuticals, Aleta BioPharma, Affinia Therapeutics, Voyager Therapeutics, Janssen, Blueprint Medicines; Financial Interests, Personal, Stocks/Shares: Artera; Financial Interests, Personal, Other, Royalties: UpToDate. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Board, Ad board participant/Consultant: Pfizer; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Novartis, Gilead, Genentech/Roche, Eisai, Sanofi, Seagen, Daiichi Sankyo, 4D Pharma, ARC Therapeutics; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol Myers Squibb, Mersana Therapeutics, Ellipses Pharma; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Other, Consultant: Blueprint Medicines; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; Financial Interests, Personal, Advisory Board, Advisory Board participation: Zentalis, OncXerna, Myovant, Bayer, Zetagen, Infinity Therapeutics, Umoja Biopharma; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; Financial Interests, Personal, Advisory Board, Advisory Board participation/consulting: Menarini/Stemline; Financial Interests, Personal, Other, Consulting: Aadi BioPharma; Financial Interests, Institutional, Funding: AstraZeneca, Eli Lilly, Pfizer, Sanofi, Seagen, Odonate, Cyclacel, Exelixis, Gilead, Bristol Myers Squibb, Eisai, Merck, Novartis, Nektar, Genentech/Roche; Financial Interests, Personal and Institutional, Invited Speaker: CytomX. A. Prat: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis, Pfizer, Oncolytics Biotech, Guardant Health, Peptomyc; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Institutional, Other, Contracted research: Boehringer, Medica Scientia inno. Research; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Leadership role: Reveal Genomics, SL.; Financial Interests, Personal, Stocks/Shares: Reveal Genomics, Oncolytics Biotech; Financial Interests, Personal, Royalties: Reveal Genomics; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation, Actitud Frente al Cáncer Foundation; Non-Financial Interests, Personal, Other, Asociación Española de Investigación sobre el Cáncer: ASEICA. O. Martinez Saez: Financial Interests, Personal, Invited Speaker: Novartis, Eisai; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Other, Travel expenses: Roche; Financial Interests, Personal, Other, Medical advisory: Reveal Genomics. All other authors have declared no conflicts of interest.