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Clinical Trial
. 2025 Oct:83:104528.
doi: 10.1016/j.breast.2025.104528. Epub 2025 Jul 4.

Does RSClin provide additional information over classic clinico-pathologic scores (PREDICT 2.1, INFLUENCE 2.0, CTS5)?

Ana-Alicia Beltran-Bless  1 , Gregory R Pond  2 , Jane Bayani  3 , Sarah L Barker  4 , Melanie Spears  3 , Elizabeth Mallon  5 , Karen J Taylor  6 , Annette Hasenburg  7 , Christos Markopoulos  8 , Luc Dirix  9 , Elma Meershoek-Klein Kranenbarg  10 , Cornelis J H van de Velde  10 , Daniel W Rea  11 , Lisa Vandermeer  12 , John Hilton  13 , John M S Bartlett  6 , Mark Clemons  14
Affiliations
Clinical Trial

Does RSClin provide additional information over classic clinico-pathologic scores (PREDICT 2.1, INFLUENCE 2.0, CTS5)?

Ana-Alicia Beltran-Bless et al. Breast. 2025 Oct.

Abstract

Purpose: Few studies have compared the performance of gene-expression profiling tests (e.g. Oncotype-Dx) to clinico-pathologic risk calculators (e.g. PREDICT 2.1, INFLUENCE 2.0, and CTS5) or tools that combine both (e.g. RSClin) in patients with early breast cancer (EBC). A large trial dataset was used to evaluate the prognostic performance of different tests based on patient outcomes.

Methods: The TEAM pathology cohort accrued samples from 4736 postmenopausal hormone positive women with EBC, treated with either exemestane or tamoxifen followed by exemestane. Oncotype-Dx-trained risk scores were previously generated by gene-expression profiling. Patient data was used to calculate various recurrence scores. Analysis was restricted to the N0/N1 population and prognostic ability of selected risk tools was assessed using Cox regression analysis and Harrell's C-statistic.

Results: Results were available for 2065 patients. There was low correlation between PREDICT 2.1 (r = -0.12), INFLUENCE 2.0 (r = 0.20), CTS5 (r = 0.16) with Oncotype-Dx-trained results. In N0 patients, RSClin had improved prognostic ability (C-statistic = 0.66) on DMFS compared to PREDICT 2.1 (0.60), INFLUENCE 2.0 (0.57), CTS-5 (0.62), and Oncotype-Dx (0.63).

Conclusion: Combining molecular and clinico-pathologic factors enhances prognostic information. However, the impact of this on actual patient management requires further prospective validation. The trial is registered with clinicaltrials.gov NCT00279448 and NCT00032136; with Netherlands Trial Register, number NTR 267; and the Ethics Commission Trial, number 27/2001.

Keywords: Adjuvant; Breast cancer; Clinical risk; Gene-expression profiling; Prognostic; RSClin.

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Conflict of interest statement

Declaration of competing interests G.R.P. has received consultancy from Takeda, Merck, Profound Medical and honoraria from AstraZeneca. J.B has received honoraria from Thermo Fisher Scientific, Nanostring Technologies and research funding from Thermo Fisher Scientific. K.T has received research funding from Exact Sciences. A.H has received consultancy from PharmaMar, Tesaro, Roche, AstraZeneca, LEO Pharma, GlaxoSmithKline/MSD, Promedicis, travel/accommodations from AstraZeneca, MedConcept and honoraria from AstraZeneca, Pfizer, Roche, Streamedup!, Tesaro, MedConcept, LEO Pharma, Celgene, Medicultus Kassel, GlaxoSmithKline, Promedicis, SoftConsultGroup. C.M. has received travel accommodations and honoraria from Exact Sciences. D.W.R has received consultancy from Genomic Health, MSD Oncology, travel accommodations from Pfizer, Daiichi Sankyo, Eisai, Novartis, honoraria from Roche, Novartis, Pfizer, Lilly, Daiichi Sankyo and research funding from Celgene, Roche, bioTheranostics. J. H. received consultancy from Bristol-Myers Squibb, Novartis, Pfizer, Puma Biotechnology, AstraZeneca, Lilly, Merck. J.B has received consultancy from Insight Genetics, BioNTech, bioTheranostics, RNA Diagnostics, Pfizer, oncoXchange, Herbert Smith Freehills Paris, OncoCyte, Ontario Institute for Cancer Research, AstraZeneca, Cerca Biotech, Tempus, leadership from MedcomXchange, travel accommodation from bioTheranostics, honoraria from bioTheranostics, MedcomXchange, and research funding from Nanostring Technologies, Stratifyer GmBH, Genoptix, Thermos Fisher Scientific, Agendia, bioTheranostics, Exact Sciences. All remaining authors have declared no conflicts of interest.

Figures

Fig. 1
Fig. 1
Consort diagram.
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