In the APT and ATEMPT trials, adjuvant paclitaxel and trastuzumab (TH) and T-DM1 were found associated with excellent long-term outcomes for patients (pts) with small, node-negative HER2-positive breast cancer (HER2+ BC), respectively. HER2DX risk score was found associated with outcomes in both trials, separately.
We conducted a retrospective analysis combining pts included in the APT and ATEMPT trials with available HER2DX data. Co-primary endpoints were associations of HER2DX with relapse-free interval (RFI) and invasive disease-free survival (iDFS). The HER2DX risk-score was evaluated i) as a continuous variable (0-100), ii) using the predefined cut-off (50), and iii) using an exploratory optimal cut-off (32). The Kaplan-Meier method and stratified Cox regression models were used to evaluate the association between HER2DX and outcomes.
In total, 471 pts receiving TH (n=324) or T-DM1 (n=147) were included in the study, most having stage I (n=432, 92%) and hormone receptor-positive disease (n=335, 75%). The median follow-up was 6.7 years (10.8 and 5.8 for APT and ATEMPT, respectively). The median HER2DX risk-score was 13.9 (IQR 4.7 - 27.0), with 5.5% and 18.3% of the pts having HER2DX high-risk disease according to the predefined and optimal cut-off, respectively. HER2DX risk score as a continuous variable was associated with RFI (HR per 10-units: 1.39, 95%CI: 1.09-1.78; p=0.009) but not with iDFS (HR per 10-units: 1.18, 0.98-1.42; p=0.09). Using the predefined cut-off (50), pts with HER2DX high-risk disease had higher RFI risk (HR: 7.33, 2.29-23.47, p<0.001), but the effect on iDFS was non-significant (HR: 2.78, 0.97-7.95, p=0.057). In multivariable analysis of RFI, HER2DX remained statistically significant after adjustment for hormone receptor status and tumor size (HR: 7.89, 2.06-30.22, p=0.003). The optimal cut-off (32) distinguished pts with low-risk (7-year RFI of 98.2%; 96.7%-99.6%) from high-risk disease (7-year RFI: 88.7%; 80.4%-97.8%) [delta of 9.5%], including in multivariable analysis for RFI (HR: 6.87, 2.22-21.27, p<0.001) and iDFS (HR: 2.81, 1.26-6.23, p=0.01).
The HER2DX risk score is associated with the risk of recurrence among pts with small, node-negative HER2+ breast tumors treated with adjuvant TH or T-DM1.
The authors.
Has not received any funding.
P. Tarantino: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Lilly, Gilead. P. Villagrasa Gonzalez: Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Personal, Advisory Board: Nanostring. F. Brasó-Maristany: Financial Interests, Personal, Invited Speaker: 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. A.H. Partridge: Financial Interests, Personal, Royalties, Royalties received for authorship of Breast Cancer Survivorship section: UpToDate; Non-Financial Interests, Leadership Role, co-Chair of Breast Committee: Alliance for Clinical Trials, National Cancer Institute; Non-Financial Interests, Other, Board of Directors, Member 2022-2026: ASCO. H.J. Burstein: Non-Financial Interests, Principal Investigator, Grant for clinical research: National Cancer Insti; Non-Financial Interests, Invited Speaker: Alliance for Clinical Trials in Oncology. I. Krop: Financial Interests, Personal, Advisory Board: genentech/Roche, AstraZeneca, Daiichi Sankyo, Macrogenics, Seagen; Financial Interests, Personal, Other, DSMB member: Novartis; Financial Interests, Personal, Other, DSMC member: Merck; Financial Interests, Personal, Full or part-time Employment, Spouse: PureTech, Freeline; Financial Interests, Personal, Stocks/Shares, Spouse: PureTech, Freeline; Financial Interests, Institutional, Invited Speaker: Pfizer, Macrogenics, Genentech?Roche. E.P. Winer: Financial Interests, Personal, Advisory Board: Athenex, Carrick Therapeutics, G1 Therapeutics, Genentech/Roche, Genomic Health, Gilead, GlaxoSmithKline, Jouce, Lilly, St. Lucia, Syros, Zymeworks; Non-Financial Interests, Personal, Advisory Board: Leap Therapeutics; Non-Financial Interests, Personal, Invited Speaker: ASCO. 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.