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Multicenter Study
. 2025 Apr:80:104415.
doi: 10.1016/j.breast.2025.104415. Epub 2025 Feb 19.

Validation of the CTS5 in four prospective, multicenter, randomized ABCSG trials

Kerstin Wimmer  1 , Dominik Hlauschek  2 , Marija Balic  3 , Georg Pfeiler  4 , Richard Greil  5 , Christian F Singer  4 , Stefan Halper, Günther Steger  6 , Christoph Suppan  3 , Simon Peter Gampenrieder  5 , Ruth Helfgott  7 , Daniel Egle  8 , Martin Filipits  9 , Raimund Jakesz  10 , Lidija Sölkner  2 , Christian Fesl  2 , Michael Gnant  11 , Florian Fitzal  12 ; Austrian Breast & Colorectal Cancer Study Group
Affiliations
Multicenter Study

Validation of the CTS5 in four prospective, multicenter, randomized ABCSG trials

Kerstin Wimmer et al. Breast. 2025 Apr.

Abstract

Background: The Clinical Treatment Score post-5 years (CTS5) is a clinicopathological tool designed to estimate late distant recurrence (LDR) in hormone receptor-positive (HR+) breast cancer patients after 5 years of adjuvant endocrine therapy (ET). While intended as a prognostic algorithm, its predictive value for ET extension remains uncertain.

Methods: The score was calculated in 4931 patients from four prospective randomized ABCSG trials (ABCSG-6, -6a, -8, and -16) with 250 LDR events. We assessed its prognostic power, calibration accuracy, and predictive value. Time to LDR was analyzed using Cox regression models.

Results: In our cohorts, the CTS5 provided prognostic information whether used as a continuous or categorical score. In the ABCSG-8 cohort (n = 2054) and the combined ABCSG-6+8 cohort (n = 3308), a higher continuous score was significantly associated with increased LDR risk. The categorical CTS5 showed that high-risk patients had significantly higher LDR rates compared to low- or intermediate-risk patients. The score slightly overestimated LDR risk, regardless of predicted risk. Although no significant predictive value was found on the relative scale, an absolute LDR risk reduction of 23.4 % was found in patients with a high CTS5 of 5 when extended ET was administered additional five than two years. In patients with a CTS5 of 2, no benefit was found when ET was extended to 10 instead of 7 years.

Conclusion: The CTS5 is a valid tool for LDR risk stratification in HR + breast cancer, but should be used cautiously for determining benefits from ET extension, as no significant predictive value was found.

Keywords: Adjuvant setting; CTS5; Endocrine therapy; Late distant recurrence; Predictive value.

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Conflict of interest statement

Declaration of competing interest All authors have completed and submitted the Declaration of Interest form. Marija Balic reported having received research funding from Amgen, Celgene, Eli Lilly, Novartis, Roche, Pfizer, Samsung and has an advisory role at Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Samsung and Gilead. Marija Balic also reports to be part of the speakers bureau at Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen and Gilead. Daniel Egle reports having received honoraria, travel grants and is a member of Advisory Boards at Amgen, AstraZeneca, Daiichi-Sankyo, Gilead, Lilly, MSD, Novartis, Pfizer, Pierre-Fabre, Roche, Sandoz, Seagen and Sirius. Martin Filipits has received honoraria from Astra Zeneca, Biomedica, Biorad, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, and Pfizer. Florian Fitzal reports a role as Editor for Oncoplastic Surgery part I and II: Springer and having received travel and scientific support from Comesa (Mentor), Novartis, Roche, Astra Zeneca, Pfizer, Myriad, Nanostring, Bondimed (Polytech, Integra) and Eli Lilly. Florian Fitzal has also an Advisory Role for Pfizer, Astra Zeneca, Lilly and Roche and is founder of the Breast analyzing tool (BAT): breastanalyzing. com. Simon Peter Gampenrieder reports having received speaking and lecture fees from Novartis Pharma AG, Roche, Bristol Myers Squibb Co, AstraZeneca Pharmaceuticals LP, Merck Sharp & Dohme UK Ltd, Pfizer Inc, Eli Lilly and Company, Seagen Inc; travel reimbursement from Novartis Pharma AG, Roche, Pfizer Inc, Amgen Inc, Shire, Bayer AG, Celgene GmbH, Daiichi Sankyo Inc and funding grants from Roche. Also, Simon Peter Gampenrieder reports to have a consulting and advisory role at Roche, Bristol Myers Squibb Co, AstraZeneca Pharmaceuticals LP, Merck Sharp & Dohme UK Ltd, Eli Lilly and Company and Seagen Inc. Michael Gnant reports having received personal fees/travel support from Amgen, DaiichiSankyo, AstraZeneca, Eli Lilly, LifeBrain, Nanostring, Novartis, PierreFabre, MSD, also an immediate family member is employed by Sandoz. Richard Greil reports having received research funding and honoraria from Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, Abbvie, Gilead and Daiichi Sankyo. In addition, honoraria were also received from Sanofi. Richard Greil has also a consulting or Advisory Role at Celgene, Novartis, Roche, BMS, Takeda, Abbvie, Astra Zeneca, Janssen, MSD, Merck, Gilead, Daiichi Sankyo and Sanofi. Richard Greil was supported for travel, accommodations, expenses by Roche, Amgen, Janssen, Astra Zeneca, Novartis, MSD, Celgene, Gilead, BMS, Abbvie and Daiichi Sankyo. Georg Pfeiler reports having received grants and honoraria from Pfizer, Roche, Seagen, Daiichi, Lilly, Novartis, AstraZeneca, MSD and UCB. Christian F. Singer reports that administrative support, statistical analysis, and writing assistance were provided by Medical University of Vienna. Christian F singer reports a relationship with the Medical University of Vienna that includes board membership, consulting or advisory, funding grants, speaking and lecture fees, and travel reimbursement. Following authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper: Kerstin Wimmer, Dominik Hlauschek, Günther Steger, Christoph Suppan, Ruth Helfgott, Raimund Jakesz, Lidija Sölkner, Christian Fesl.

Figures

Fig. 1
Fig. 1
Patient flow of the patients included in this analysis.
Fig. 2
Fig. 2
5- to 10-year DR-free survival curves according to the CTS5 risk categories in patients from ABCSG-8 (n = 2054).
Fig. 3
Fig. 3
Calibration plot of the CTS5 comparing the observed with the predicted LDR risk when the population of ABCSG-6+8 (n = 3308) was divided into quintiles according to the CTS5 score.
Fig. 4
Fig. 4
Five-year LDR risk (starting at randomization to ABCSG-16) according to the continuous CTS5 in patients with either 2 years or 5 years of additional AI therapy. The confidence bands reflect the 95 % pointwise confidence intervals. The semi-transparent bars reflect the numbers of patients in each CTS5 value group.
See this image and copyright information in PMC

References

    1. Pedersen R.N., Esen B.O., Mellemkjaer L., Christiansen P., Ejlertsen B., Lash T.L., et al. The incidence of breast cancer recurrence 10-32 Years after primary diagnosis. J Natl Cancer Inst. 2022;114(3):391–399. - PMC - PubMed
    1. Negoita S, Ramirez-Pena E. Prevention of Late Recurrence: An Increasingly Important Target for Breast Cancer Research and Control. J Natl Cancer Inst. 2022;114(3):340–341. - PMC - PubMed
    1. Laenkholm A.V., Jensen M.B., Eriksen J.O., Rasmussen B.B., Knoop A.S., Buckingham W., et al. PAM50 risk of recurrence score predicts 10-year distant recurrence in a comprehensive Danish cohort of postmenopausal women allocated to 5 Years of endocrine therapy for hormone receptor-positive early breast cancer. J Clin Oncol. 2018;36(8):735–740. - PubMed
    1. Burstein H.J., Curigliano G., Thurlimann B., Weber W.P., Poortmans P., Regan M.M., et al. Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021. Ann Oncol. 2021;32(10):1216–1235. - PMC - PubMed
    1. Thomssen C., Balic M., Harbeck N., Gnant M. St. Gallen/Vienna 2021: a brief summary of the consensus discussion on customizing therapies for women with early breast cancer. Breast Care. 2021;16(2):135–143. - PMC - PubMed

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