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Muñoz Mateu, MontserratAuthorVidal Rodriguez, MartaAuthorMarin Menendez, AlejandroAuthorVidal Laliena, MiriamAuthorMarin-Aguilera MAuthorBrasó-Maristany FAuthorPascual TAuthorMartínez-Sáez OAuthorMunoz MAuthorVidal MAuthorAdamo BAuthorPrat ACorresponding Author

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June 12, 2023
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Article

Association of HER2DX with pathological complete response and survival outcomes in HER2-positive breast cancer

Publicated to:Annals Of Oncology. 34 (9): 783-795 - 2023-09-01 34(9), DOI: 10.1016/j.annonc.2023.05.012

Authors: Villacampa, G; Tung, NM; Pernas, S; Paré, L; Bueno-Muiño, C; Echavarría, I; López-Tarruella, S; Roche-Molina, M; del Monte-Millán, M; Marín-Aguilera, M; Brasó-Maristany, F; Waks, AG; Pascual, T; Martínez-Sáez, O; Vivancos, A; Conte, PF; Guarneri, V; Dieci, MV; Griguolo, G; Cortés, J; Llombart-Cussac, A; Muñoz, M; Vidal, M; Adamo, B; Wolff, AC; Demichele, A; Villagrasa, P; Parker, JS; Perou, CM; Fernandez-Martinez, A; Carey, LA; Mittendorf, EA; Martín, M; Prat, A; Tolaney, SM

Affiliations

- Author
Arnau de Vilanova Hospital, Universidad Católica de Valencia, Valencia, Spain. - Author
Beth Israel - Author
Beth Israel, Boston, USA. - Author
Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA - Author
Brigham & Womens Hosp, Dept Surg, Div Breast Surg - Author
Cancer Genomics Group, VHIO, Barcelona, Spain. - Author
Catalan Inst Oncol, Med Oncol Dept - Author
Dana Farber Canc Inst, Dept Med Oncol - Author
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, USA. - Author
Department of Medical Oncology, Hospital Clinic of Barcelona, Spain - Author
Department of Medical Oncology, Hospital Clinic of Barcelona, Spain. - Author
Department of Medical Oncology, Hospital General Universitario Gregorio Marañón Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. - Author
Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, CIBERONC, Madrid, Spain. - Author
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, USA. - Author
Department of Oncology, University of Pennsylvania, Philadelphia, USA. - Author
Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy - Author
Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA. - Author
Fdn Invest Biomed HU Puerta Hierro, Hosp Infanta Cristina Parla, Med Oncol Dept - Author
Harvard Med Sch - Author
Harvard Medical School, Boston, MA, USA - Author
Harvard Medical School, Boston, MA, USA. - Author
Harvard Medical School, Boston, MA, USA. Electronic address: sara_tolaney@dfci.harvard.edu. - Author
Hosp Clin Barcelona, Dept Med Oncol - Author
Hosp Clin Barcelona, Med Oncol Dept, Villarroel 170,Stair 2-5 Floor - Author
Hosp Gen Univ Gregorio Maranon, CiberOnc, Inst Invest Sanitaria Gregorio Maranon, Dept Med Oncol - Author
Institute of Oncology (IOB)-Quirón, Barcelona, Spain. Electronic address: alprat@clinic.cat. - Author
International Breast Cancer Center, Pangaea Oncology, Quirónsalud Group, Barcelona, Spain. - Author
IRCCS, Ist Oncol Veneto - Author
Istituto Oncologico Veneto, IRCCS, Padova, Italy. - Author
Johns Hopkins Univ, Sch Med, Dept Oncol - Author
Medical Oncology Department, Catalan Institute of Oncology, 08908, L'Hospitalet de Llobregat, Barcelona, Spain. - Author
Medical Oncology Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañon (IiSGM), CIBERONC, Geicam, Universidad Complutense, 28007 Madrid, Spain. - Author
Medical Oncology Department, Hospital Infanta Cristina (Parla), Fundación de Investigación Biomédica del H.U. Puerta de Hierro, Majadahonda, 28009 Madrid, Spain. - Author
Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA - Author
Oncology Data Science, Vall d'Hebron Institute of Oncology, Barcelona, Spain. - Author
Quironsalud Grp, Pangaea Oncol, Int Breast Canc Ctr - Author
Reveal Genom - Author
Reveal Genomics, Barcelona, Spain - Author
Reveal Genomics, Barcelona, Spain. - Author
SOLTI Breast Cancer Research Group, Barcelona, Spain - Author
Translational Genomics and Targeted Therapies in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain - Author
Univ Catol Valencia, Arnau Vilanova Hosp - Author
Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet - Author
Univ Penn, Dept Oncol - Author
Vall dHebron Inst Oncol, Oncol Data Sci - Author
VHIO, Canc Genom Grp - Author
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Abstract

The HER2DX genomic test predicts pathological complete response (pCR) and survival outcome in early-stage HER2+ breast cancer. Here, we evaluated the association of HER2DX scores with 1) pCR according to hormone receptor status and various treatment regimens, and 2) survival outcome according to pCR status.Seven neoadjuvant cohorts with HER2DX and clinical individual patient data were evaluated (DAPHNe, GOM-HGUGM-2018-05, CALGB-40601, ISPY-2, BiOnHER, NEOHER and PAMELA). All patients were treated with neoadjuvant trastuzumab (n=765) in combination with pertuzumab (n=328), lapatinib (n=187) or without a second anti-HER2 drug (n=250). Event-free survival (EFS) and overall survival (OS) outcomes were available in a combined series of 268 patients (i.e., NEOHER and PAMELA) with a pCR (n=118) and without a pCR (n=150). Cox models were adjusted to evaluate whether HER2DX can identify patients with low- or high-risk beyond pCR status.HER2DX pCR score was significantly associated with pCR in all patients (odds-ratio [OR] per 10-unit increase=1.59, 95% CI 1.43-1.77; AUC=0.75), with or without dual HER2 blockade. A statistically significant increase in pCR rate due to dual HER2 blockade over trastuzumab-only was observed in HER2DX pCR-high tumors treated with chemotherapy (OR=2.56, 1.29-5.20). A statistically significant increase in pCR rate due to multi-agent chemotherapy over a single taxane was observed in HER2DX pCR-medium tumors treated with dual HER2 blockade (OR=3.11, 1.54-6.49). The pCR rates in HER2DX pCR-low tumors were ≤30.0% regardless of treatment administered. After adjusting by pCR status, patients identified as HER2DX low-risk had better EFS (p<0.001) and OS (p=0.006) compared to patients with HER2DX high-risk.HER2DX pCR-score and risk-score might help identify ideal candidates to receive neoadjuvant dual HER2 blockade in combination with a single taxane in early-stage HER2+ breast cancer.Copyright © 2023. Published by Elsevier Ltd.

Keywords

AdultAgedAntineoplastic agentAntineoplastic combined chemotherapy protocolsArticleBiomarkerBreast cancerBreast neoplasmsBreast tumorCancer stagingCancer survivalClinical assessmentClinical evaluationClinical featureCohort analysisComparative studyControlled studyDisease associationEarly cancerEpidermal growth factor receptor 2Event free survivalFemaleFollow upGeneticsGenomicsHer2Her2dxHer2dx scoreHigh risk patientHumanHuman epidermal growth factor receptor 2 positive breast cancerHumansLapatinibLong term careMajor clinical studyNeoadjuvantNeoadjuvant chemotherapyNeoadjuvant therapyOverall survivalPathological complete responsePathologyPertuzumabRandomized controlled trialReceptor, erbb-2Risk assessmentTaxaneTaxoidTaxoidsTrastuzumabTreatment outcomeTreatment responseTumor volume

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Annals Of Oncology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2023, it was in position 4/322, thus managing to position itself as a Q1 (Primer Cuartil), in the category Oncology. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 5.8. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 2.97 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 19.87 (source consulted: Dimensions Sep 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-09-08, the following number of citations:

  • WoS: 32
  • Scopus: 19
  • Europe PMC: 6

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-09-08:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 29.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 29 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 10.7.
  • The number of mentions on the social network X (formerly Twitter): 16 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Israel; Italy; Timor-Leste; United States of America.

the author responsible for correspondence tasks has been Prat Aparicio, Aleix.