Top

Breast Cancer Research and Treatment

Published in:

Open Access 01-02-2021 | Breast Cancer | Clinical trial

Clinical validity of clinical treatment score 5 (CTS5) for estimating risk of late recurrence in unselected, non-trial patients with early oestrogen receptor-positive breast cancer

Authors: Juliet Richman, Alistair Ring, Mitch Dowsett, Ivana Sestak

Published in: Breast Cancer Research and Treatment | Issue 1/2021

Abstract

Purpose

Clinical Treatment Score at 5 years (CTS5) is a prognostic tool to estimate distant recurrence (DR) risk after 5 years of endocrine therapy for postmenopausal women with oestrogen receptor-positive (ER-positive) breast cancer.

Methods

The validity of CTS5 was tested in a retrospective cohort of patients diagnosed with early ER-positive breast cancer. The primary endpoint was DR in years 5–10. The primary analysis cohort consisted of postmenopausal women, with premenopausal women as a secondary analysis cohort. Cox regression models were used to determine the prognostic value of CTS5 and Kaplan–Meier curves were used with associated 10-year DR risks (%).

Results

2428 women were included with a median follow-up of 13.4 years. The CTS5 was significantly prognostic in both postmenopausal (N = 1662, HR = 2.18 95% CI (1.78–2.67)) and premenopausal women (N = 766, HR = 1.84 95% CI (1.32–2.56)). The 10-year DR risks were 2.9% (1.9–4.5), 7.2% (5.3–9.9), and 12.9% (10.0–16.7) for low, intermediate and high risk in postmenopausal women and 3.8% (2.2–6.7), 6.9% (4.4–10.8), and 11.1% (7.4–16.5) in premenopausal women, respectively. The number of observed DRs was significantly greater than expected in those predicted to be at high risk by CTS5 but this discordance was lost when those receiving more than 60 months of endocrine therapy were excluded.

Conclusions

The CTS5 demonstrated clinical validity for predicting late DR within a large cohort of unselected postmenopausal patients but less so in premenopausal patients. Calibration of the CTS5 was good in patients who did not receive extended endocrine therapy. The CTS5 low-risk cohort has risk of DR so low as to not warrant extended endocrine therapy.

Available only for authorised users

Pan H, Gray R, Braybrooke J, Davies C, Taylor C, McGale P, Peto R, Pritchard KI, Bergh J, Dowsett M, Hayes DF, Ebctcg (2017) 20-year risks of breast-Cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med 377(19):1836–1846CrossRef

Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V, Abraham M, Alencar VHM, Badran A, Bonfill X, Bradbury J, Clarke M, Collins R, Davis SR, Delmestri A, Forbes JF, Haddad P, Hou MF, Inbar M, Khaled H, Kielanowska J, Kwan WH, Mathew BS, Mittra I, Muller B, Nicolucci A, Peralta O, Pernas F, Petruzelka L, Pienkowski T, Radhika R, Rajan B, Rubach MT, Tort S, Urrutia G, Valentini M, Wang Y, Peto R, G. Adjuvant Tamoxifen: Longer Against Shorter Collaborative (2013) Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 381(9869):805–816CrossRef

Gray RG, Rea D, Handley K (2013) aTTom: long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6,953 women with early breast cancer. J Clin Oncol 31(18):5CrossRef

Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Pater JL (2005) Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst 97(17):1262–1271CrossRef

Goss PE, Ingle JN, Pritchard KI, Robert NJ, Muss H, Gralow J, Gelmon K, Whelan T, Strasser-Weippl K, Rubin S, Sturtz K, Wolff AC, Winer E, Hudis C, Stopeck A, Beck JT, Kaur JS, Whelan K, Tu D, Parulekar WR (2016) Extending aromatase-inhibitor adjuvant therapy to 10 years. N Engl J Med 375(3):209–219CrossRef

Ohtani S, Iijima K, Higaki K, Sato Y, Hozumi Y, Hasegawa Y, Takei H, Tanaka M, Yagata H, Masuoka H, Tanabe M, Egawa C, Komoike Y, Saji S, Nakamura T, Yanagita Y, Ohtsu H, Mukai H, Iwase T (2019) Abstract GS3-04: a prospective randomized multi-center open-label phase III trial of extending aromatase-inhibitor adjuvant therapy to 10 years - results from 1697 postmenopausal women in the N-SAS BC 05 trial: Arimidex extended adjuvant randomized study (AERAS). Cancer Res 79(4 Supplement):GS3-04-GS3-04

Mamounas EP, Bandos H, Lembersky BC, Jeong JH, Geyer CE Jr, Rastogi P, Fehrenbacher L, Graham ML, Chia SK, Brufsky AM, Walshe JM, Soori GS, Dakhil SR, Seay TE, Wade JL 3rd, McCarron EC, Paik S, Swain SM, Wickerham DL, Wolmark N (2019) Use of letrozole after aromatase inhibitor-based therapy in postmenopausal breast cancer (NRG oncology/NSABP B-42): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 20(1):88–99CrossRef

Dowsett M, Sestak I, Regan MM, Dodson A, Viale G, Thurlimann B, Colleoni M, Cuzick J (2018) Integration of clinical variables for the prediction of late distant recurrence in patients with Estrogen receptor-positive breast cancer treated with 5 years of endocrine therapy: CTS5. J Clin Oncol 36(19):1941–1948CrossRef

Blok EJ, Kroep JR, Meershoek-Klein Kranenbarg E, Duijm-de Carpentier M, Putter H, van den Bosch J, Maartense E, van Leeuwen-Stok AE, Liefers GJ, Nortier JWR, Rutgers EJT, van de Velde CJH, I.S. Group (2018) Optimal duration of extended adjuvant endocrine therapy for early breast cancer; results of the IDEAL trial (BOOG 2006-05). J Natl Cancer Inst 110(1)

10.

Colleoni M, Luo W, Karlsson P, Chirgwin J, Aebi S, Jerusalem G, Neven P, Hitre E, Graas MP, Simoncini E, Kamby C, Thompson A, Loibl S, Gavila J, Kuroi K, Marth C, Muller B, O’Reilly S, Di Lauro V, Gombos A, Ruhstaller T, Burstein H, Ribi K, Bernhard J, Viale G, Maibach R, Rabaglio-Poretti M, Gelber RD, Coates AS, Di Leo A, Regan MM, Goldhirsch A, S. Investigators (2018) Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 19(1):127–138CrossRef

11.

Gnant M, Steger G, Greil R, Fitzal F, Mlineritsch B, Manfreda D, Tausch C, Balic M, Dubsky P, Moik M, Thaler J, Egle D, Bjelic-Radisic V, Selim R, Exner R, Singer C, Melbinger E, Haslbauer F, Stöger H, Helfgott R, Sevelda P, Trapl H, Wette V, Sölkner L, Jakesz R (2018) Abstract GS3-01: a prospective randomized multi-center phase-III trial of additional 2 versus additional 5 years of anastrozole after initial 5 years of adjuvant endocrine therapy – results from 3,484 postmenopausal women in the ABCSG-16 trial. Cancer Res 78(4 Supplement)

12.

Noordhoek I, Blok EJ, Meershoek-Klein Kranenbarg E, Putter H, Duijm-de Carpentier M, Rutgers EJT, Seynaeve C, Bartlett JMS, Vannetzel JM, Rea DW, Hasenburg A, Paridaens R, Markopoulos CJ, Hozumi Y, Portielje JEA, Kroep JR, van de Velde CJH, Liefers GJ (2020) Overestimation of late distant recurrences in high-risk patients with ER-positive breast cancer: validity and accuracy of the CTS5 risk score in the TEAM and IDEAL trials. J Clin Oncol:JCO1902427

13.

Sestak, I., Crager M., J. Cuzick, et al (2019) Validation of the clinical treatment score post 5 years (CTS5) in women with hormone receptor positive, HER2-negative, node-negative disease from the TAILORx study. In SABCS, TX, USA

14.

Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Revil C, Jones A (2009) Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol 27(33):5529–5537CrossRef

15.

Strasser-Weippl K, Horick N, Smith IE, O’Shaughnessy J, Ejlertsen B, Boyle F, Buzdar AU, Fumoleau P, Gradishar W, Martin M, Moy B, Piccart-Gebhart M, Pritchard KI, Lindquist D, Rappold E, Finkelstein DM, Goss PE (2015) Long-term hazard of recurrence in HER2+ breast cancer patients untreated with anti-HER2 therapy. Breast Cancer Res 17:56CrossRef

16.

Cameron D, Piccart-Gebhart MJ, Gelber RD, Procter M, Goldhirsch A, de Azambuja E, Castro G Jr, Untch M, Smith I, Gianni L, Baselga J, Al-Sakaff N, Lauer S, McFadden E, Leyland-Jones B, Bell R, Dowsett M, Jackisch C, T. Herceptin Adjuvant Trial Study (2017) 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet 389(10075):1195–1205CrossRef

17.

Filipits M, Nielsen TO, Rudas M, Greil R, Stoger H, Jakesz R, Bago-Horvath Z, Dietze O, Regitnig P, Gruber-Rossipal C, Muller-Holzner E, Singer CF, Mlineritsch B, Dubsky P, Bauernhofer T, Hubalek M, Knauer M, Trapl H, Fesl C, Schaper C, Ferree S, Liu S, Cowens JW, Gnant M, Austrian B, G. Colorectal Cancer Study (2014) The PAM50 risk-of-recurrence score predicts risk for late distant recurrence after endocrine therapy in postmenopausal women with endocrine-responsive early breast cancer. Clin Cancer Res 20(5):1298–1305CrossRef

18.

Sestak I, Cuzick J, Dowsett M, Lopez-Knowles E, Filipits M, Dubsky P, Cowens JW, Ferree S, Schaper C, Fesl C, Gnant M (2015) Prediction of late distant recurrence after 5 years of endocrine treatment: a combined analysis of patients from the Austrian breast and colorectal cancer study group 8 and arimidex, tamoxifen alone or in combination randomized trials using the PAM50 risk of recurrence score. J Clin Oncol 33(8):916–922CrossRef

19.

Sgroi DC, Sestak I, Cuzick J, Zhang Y, Schnabel CA, Schroeder B, Erlander MG, Dunbier A, Sidhu K, Lopez-Knowles E, Goss PE, Dowsett M (2013) Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population. Lancet Oncol 14(11):1067–1076CrossRef

20.

Buus R, Sestak I, Kronenwett R, Denkert C, Dubsky P, Krappmann K, Scheer M, Petry C, Cuzick J, Dowsett M (2016) Comparison of EndoPredict and EPclin with Oncotype DX recurrence score for prediction of risk of distant recurrence after endocrine therapy. J Natl Cancer Inst 108(11)

Title: Clinical validity of clinical treatment score 5 (CTS5) for estimating risk of late recurrence in unselected, non-trial patients with early oestrogen receptor-positive breast cancer
Authors: Juliet Richman
Alistair Ring
Mitch Dowsett
Ivana Sestak
Publication date: 01-02-2021
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Estrogens
Published in: Breast Cancer Research and Treatment / Issue 1/2021
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-020-06013-6

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2021

HDAC6 inhibition enhances the anti-tumor effect of eribulin through tubulin acetylation in triple-negative breast cancer cells

Association between VEGF single nucleotide polymorphism and breast cancer in the Northern China Han population

Drug use disorder and risk of incident and fatal breast cancer: a nationwide epidemiological study

N-myristoyltransferase proteins in breast cancer: prognostic relevance and validation as a new drug target

Relationships between pathological factors and long-term outcomes in patients enrolled in two prospective randomized controlled trials comparing the efficacy of oral tegafur–uracil with CMF (N·SAS-BC 01 trial and CUBC trial)

Cancer stem cell transcriptome landscape reveals biomarkers driving breast carcinoma heterogeneity

Keynote webinar | Spotlight on antibody–drug conjugates in cancer