Abstract 12P
Background
HER2DX is a 27-gene assay for early-stage HER2+ breast cancer based on clinical data and the expression of 4 signatures (immune, proliferation, luminal, and HER2). Here we evaluated the utility of HER2DX in HER2+ IBC for the first time.
Methods
Standardized HER2DX was evaluated centrally on baseline pre-treatment tumors from a prospective phase II clinical trial (NCT01796197), in which patients with HER2+ IBC were treated with neoadjuvant paclitaxel, trastuzumab and pertuzumab (THP) x 16 weeks. The primary aim of this correlative analysis was to evaluate the pCR rates (ypT0/isN0) according to HER2DX pCR-score pre-defined cutoffs (i.e., low, medium, and high). Secondary objectives were to compare the HER2DX scores and signatures in IBC vs. stage II-III HER2+ non-IBC treated with neoadjuvant THP x 12 weeks on trial (NCT03716180). Descriptive statistics were used. Means between the two groups were compared using a Student´s t-test.
Results
HER2DX was evaluated in 23 patients with HER2+ IBC (Table). In IBC, the pCR rates in HER2DX pCR-high, pCR-med and pCR-low groups were 75.0% (3/4; 95% CI 19.4-99.4), 45.5% (5/11; 16.7-76.7) and 25.0% (2/8; 3.2-65.1), respectively. HER2DX high-risk in IBC represented 95.7% of the patients. Compared to non-IBC, IBC had a lower % of HER2DX pCR-high disease, higher % of HER2DX pCR-medium, and similar % of HER2DX pCR-low disease. Among the 4 HER2DX signatures, the HER2 amplicon was expressed at lower values in IBC vs. non-IBC (p=0.004), despite a similar % of HER2 3+ disease. Table: 12P
| Study | IBC | non-IBC |
| N | 23 | 80 |
| HER2 IHC 3+ | 19/21 (90.5%) | 68/78 (87.2%) |
| Clinical T4 | 23 (100%) | 0 |
| Clinical nodal + status | 21 (91.3%) | 28 (35%) |
| Hormone receptor + | 12 (52.2%) | 56 (70%) |
| pCR rate | 10 (43.5%) | 48 (60%) |
| HER2DX high risk-score | 22 (95.7%; 78.1-99.9%) | 39 (48.8%; 37.4-60.2%) |
| HER2DX pCR-score | ||
| - Low | 8 (34.8%; 16.4-57.3%) | 31(38.8%; 28.1-50.3%) |
| - Medium | 11 (47.8%; 26.8-69.4%) | 22 (27.5%;18.1-38.6%) |
| - High | 4 (17.4%; 4.9-38.8%) | 27 (33.8%; 23.6-45.2%) |
Conclusions
HER2DX pCR-high designation may be less frequent in HER2+ IBC compared to HER2+ non-IBC. Lower mRNA expression of HER2 amplicon genes, and higher tumor burden at diagnosis, might explain the differences observed in the distribution of HER2DX scores and signatures between HER2+ IBC and non-IBC.
Clinical trial identification
NCT01796197.
Legal entity responsible for the study
The authors.
Funding
Reveal Genomics.
Disclosure
F. Lynce: Financial Interests, Personal and Institutional, Advisory Board, PI of clinical trial: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer, Merck, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Incyte, Eisai, CytomX. F. Brasó-Maristany: Financial Interests, Personal, Invited Speaker: Reveal Genomics. A.G. Waks: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Genentech, Macrogenics, Merck. P. Villagrasa Gonzalez: Financial Interests, Personal, Full or part-time Employment: Reveal Genomics; Financial Interests, Personal, Other, Co-Founder: Reveal Genomics. G. Villacampa: Financial Interests, Personal, Invited Speaker, Invited speaker in a course: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Invited speaker in an internal training: Pierre Fabrer, GSK; Financial Interests, Personal, Invited Speaker, Internal discussion about the interpretation of some published results: Pfizer; Financial Interests, Personal, Other, Collaborations with specific projects: Reveal Genomics. L. Pare Brunet: Financial Interests, Institutional, Full or part-time Employment: Reveal Genomics S.L.; Financial Interests, Institutional, Other, Patent pending: In vitro method for the prognosis of patients suffering from HER2-positive breast cancer - 905333: Reveal Genomics S.L. C.M. Perou: Financial Interests, Personal, Invited Speaker: GeneCentric Therapeutics; Financial Interests, Personal, Stocks/Shares: GeneCentric Therapeutics, Bioclassifier LLC, Reveal Genomics; Financial Interests, Personal, Royalties, from PAM50 licensing: Bioclassifier LLC; Financial Interests, Personal, Royalties: GeneCentric Therapeutics; Non-Financial Interests, Advisory Role: GeneCentric Therapeutics, Bioclassifier LLC, Reveal Genomics. J. Parker: Financial Interests, Personal, Other, Advisory: Reveal Genomics, Bristol Myers Squibb; Financial Interests, Personal, Full or part-time Employment: LifeEdit Therapeutics; Financial Interests, Personal, Ownership Interest: Reveal Genomics, GeneCentric; Financial Interests, Personal, Royalties: Veracyte. A. Vivancos: Financial Interests, Personal, Advisory Board: Roche, Bristol Meyers Squibb, Guardant Health, Bayer, Incyte; Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Bristol Meyers Squibb, Roche, Incyte. S. Pernas Simon: Financial Interests, Personal, Advisory Board: Seagen, AstraZeneca- Daiichi Sankyo, Pierre-Fabre, Pfizer; Financial Interests, Personal, Invited Speaker: Lilly, Novartis, Eisai, Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Novartis, Daiichi-Sankyo; Non-Financial Interests, Invited Speaker: SOLTI. E.P. Winer: Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Personal, Advisory Board: Athenex, Carrick Therapeutics, G1 Therapeutics, Genentech/Roche, Genomic Health, Gilead, GlaxoSmithKline, Jounce, Lilly, St Lucia, Syros, Zymeworks; Non-Financial Interests, Personal, Advisory Board, non-paid: Leap Therapeutics; Other, Personal, Leadership Role, President: ASCO. E.A. Mittendorf: Financial Interests, Personal, Advisory Board: Merck, BioNTech; Financial Interests, Institutional, Research Grant, I have a grant from SU2C funded by Roche/Genentech that supports the conduct of a clinical trial: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Gillead provides clinical trial support to my institution for a study that I am the PI on: Gillead; Financial Interests, Personal, Invited Speaker: Roche/Genentech, BMS; Non-Financial Interests, Invited Speaker: American Society of Clinical Oncology; Non-Financial Interests, Advisory Role, I serve in an advisory role as a Komen Scholar: Komen for the Cure. 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. 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. All other authors have declared no conflicts of interest.