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Impact on the Sustainable Development Goals (SDGs)

Analysis of institutional authors

Vidal Rodriguez, MartaAuthorMartínez-Sáez OAuthorPascual TAuthorBrasó-Maristany FAuthorChic NAuthorGonzalez-Farre BAuthorSanfeliu EAuthorRodriguez AAuthorMartinez DAuthorGalvan PAuthorSchettini FAuthorConte BAuthorVidal MAuthorAdamo BAuthorMartinez AAuthorMunoz MAuthorPrat ACorresponding Author

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February 7, 2021
Publications
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Article

Circulating tumor DNA dynamics in advanced breast cancer treated with CDK4/6 inhibition and endocrine therapy

Publicated to: NPJ Breast Cancer. 7 (1): 8- - 2021-02-03 7(1), DOI: 10.1038/s41523-021-00218-8

Authors:

Martinez-Saez, Olga; Pascual, Tomas; Braso-Maristany, Fara; Chic, Nuria; Gonzalez-Farre, Blanca; Sanfeliu, Esther; Rodriguez, Adela; Martinez, Debora; Galvan, Patricia; Rodriguez, Anna Belen; Schettini, Francesco; Conte, Benedetta; Vidal, Maria; Adamo, Barbara; Martinez, Antoni; Munoz, Montserrat; Moreno, Reinaldo; Villagrasa, Patricia; Salvador, Fernando; Ciruelos, Eva M; Faull, Iris; Odegaard, Justin I; Prat, Aleix
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Affiliations

Guardant Health, Inc. - Author
Hospital Clinic Barcelona - Author
Hospital Universitario 12 de octubre - Author
Institut d'Investigacions Biomèdiques August Pi i Sunyer - IDIBAPS - Author
Ospedale Policlinico San Martino - Author
SOLTI Breast Cancer Research Group - Author
The University of North Carolina at Chapel Hill - Author
Universita degli Studi di Napoli Federico II - Author
Universitat de Barcelona - Author
‎ August Pi i Sunyer Biomed Res Inst IDIBAPS, Translat Genom & Targeted Therapies Solid Tumors, Barcelona, Spain - Author
‎ Guardant Hlth Inc, Redwood City, CA USA - Author
‎ Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain - Author
‎ Hosp Clin Barcelona, Dept Pathol, Barcelona, Spain - Author
‎ Hosp Univ 12 Octubre, Dept Med Oncol, Madrid, Spain - Author
‎ IRCCS Osped Policlin San Martino, UO Oncol Med, Dept Med Oncol, Genoa, Italy - Author
‎ SOLTI Canc Res Grp, Barcelona, Spain - Author
‎ Univ Barcelona, Dept Med, Barcelona, Spain - Author
‎ Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27515 USA - Author
‎ Univ Naples Federico II, Dept Clin Med & Surg, Naples, Italy - Author
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Abstract

© 2021, The Author(s). Circulating tumor DNA (ctDNA) levels may predict response to anticancer drugs, including CDK4/6 inhibitors and endocrine therapy combinations (CDK4/6i+ET); however, critical questions remain unanswered such as which assay or statistical method to use. Here, we obtained paired plasma samples at baseline and week 4 in 45 consecutive patients with advanced breast cancer treated with CDK4/6i+ET. ctDNA was detected in 96% of cases using the 74-gene Guardant360 assay. A variant allele fraction ratio (VAFR) was calculated for each of the 79 detected mutations between both timepoints. Mean of all VAFRs (mVAFR) was computed for each patient. In our dataset, mVAFR was significantly associated with progression-free survival (PFS). Baseline VAF, on-treatment VAF or absolute changes in VAF were not associated with PFS, nor were CA-15.3 levels at baseline, week 4 or the CA-15.3 ratio. These findings demonstrate that ctDNA dynamics using a standardized multi-gene panel and a unique methodological approach predicts treatment outcome. Clinical trials in patients with an unfavorable ctDNA response are needed.
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Keywords

Good health and well-being

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal NPJ Breast Cancer 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, 2021, it was in position 50/245, thus managing to position itself as a Q1 (Primer Cuartil), in the category Oncology.

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: 1.87. 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 13, 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2026-04-04, the following number of citations:

  • WoS: 32
  • Scopus: 15
  • Europe PMC: 13
  • Open Alex: 18
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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 2026-04-04:

  • 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: 52.
  • 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: 52 (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: 9.
  • The number of mentions on the social network X (formerly Twitter): 13 (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.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: http://hdl.handle.net/11579/192940
Continuing with the social impact of the work, it is important to emphasize that, due to its content, it can be assigned to the area of interest of ODS 3 - Good Health And Well-being, with a probability of 87% according to the mBERT algorithm developed by Aurora University.
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Leadership analysis of institutional authors

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

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Martínez Sáez, Olga) and Last Author (Prat Aparicio, Aleix).

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

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Project objectives

El presente estudio tiene como objetivo principal analizar la dinámica del ADN tumoral circulante (ctDNA) en pacientes con cáncer de mama avanzado tratados con inhibidores de CDK4/6 y terapia endocrina. Se busca evaluar la capacidad predictiva del ctDNA para la respuesta al tratamiento mediante la comparación de muestras plasmáticas en diferentes momentos. Además, se pretende determinar la asociación entre la media de las razones de fracción alélica variante (mVAFR) y la supervivencia libre de progresión (PFS). También se aspira a caracterizar la eficacia de un panel multigénico estandarizado y un enfoque metodológico específico para predecir resultados terapéuticos. Finalmente, se propone identificar la necesidad de ensayos clínicos en pacientes con respuesta desfavorable del ctDNA.
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Most relevant results

El estudio analiza la dinámica del ADN tumoral circulante (ctDNA) en pacientes con cáncer de mama avanzado tratados con inhibidores de CDK4/6 y terapia endocrina. Los resultados más relevantes son: (1) el ctDNA fue detectado en el 96% de los casos mediante el panel Guardant360 de 74 genes; (2) se calculó el cociente de fracción alélica variante (VAFR) para 79 mutaciones entre la línea base y la semana 4; (3) el promedio de todos los VAFR (mVAFR) por paciente mostró una asociación significativa con la supervivencia libre de progresión (PFS); (4) ni el VAF basal, ni el VAF durante el tratamiento, ni los cambios absolutos en VAF, ni los niveles o cocientes de CA-15.3 se relacionaron con la PFS; (5) estos resultados sugieren que la dinámica del ctDNA mediante un panel multigénico estandarizado y un método único predice el resultado del
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Awards linked to the item

This study was funded by Instituto de Salud Carlos III (PI19/01846) (to A.P.), Instituto de Salud Carlos III (PI18/01408) (to E.C.), Breast Cancer Research Foundation (to A.P.), PhD4MD (to N.C.), Fundacio La Marato TV3 (to A.P), RESCUER Horizon 2020 (to A.P.), Save the Mama (to A.P.), Pas a Pas (to A.P.), Asociacion Cancer de Mama Metastasico (to A.P.), Fundacion Cientifica Asociacion Espanola Contra el Cancer (to F.B.M.) and Fundacion SEOM (SEOM 2018 Grant: Fellowship for Training in Research in Reference Centers) (to T.P.). The study was designed by investigators from Hospital Clinic. Funding sources had no role in the design and conduction of this study, and in the analysis and interpretation of data. Guardant Health provided the assay. All authors had full access to all data in the study and had final responsibility for the decision to submit for publication.
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