Cargando…

Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial

BACKGROUND: The prospective phase 3 PlanB trial used the Oncotype DX(®) Recurrence Score(®) (RS) to define a genomically low-risk subset of clinically high-risk pN0-1 early breast cancer (EBC) patients for treatment with adjuvant endocrine therapy (ET) alone. Here, we report five-year data evaluatin...

Descripción completa

Detalles Bibliográficos
Autores principales: Nitz, Ulrike, Gluz, Oleg, Christgen, Matthias, Kates, Ronald E., Clemens, Michael, Malter, Wolfram, Nuding, Benno, Aktas, Bahriye, Kuemmel, Sherko, Reimer, Toralf, Stefek, Andrea, Lorenz-Salehi, Fatemeh, Krabisch, Petra, Just, Marianne, Augustin, Doris, Liedtke, Cornelia, Chao, Calvin, Shak, Steven, Wuerstlein, Rachel, Kreipe, Hans H., Harbeck, Nadia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336763/
https://www.ncbi.nlm.nih.gov/pubmed/28664507
http://dx.doi.org/10.1007/s10549-017-4358-6
_version_ 1783388112286646272
author Nitz, Ulrike
Gluz, Oleg
Christgen, Matthias
Kates, Ronald E.
Clemens, Michael
Malter, Wolfram
Nuding, Benno
Aktas, Bahriye
Kuemmel, Sherko
Reimer, Toralf
Stefek, Andrea
Lorenz-Salehi, Fatemeh
Krabisch, Petra
Just, Marianne
Augustin, Doris
Liedtke, Cornelia
Chao, Calvin
Shak, Steven
Wuerstlein, Rachel
Kreipe, Hans H.
Harbeck, Nadia
author_facet Nitz, Ulrike
Gluz, Oleg
Christgen, Matthias
Kates, Ronald E.
Clemens, Michael
Malter, Wolfram
Nuding, Benno
Aktas, Bahriye
Kuemmel, Sherko
Reimer, Toralf
Stefek, Andrea
Lorenz-Salehi, Fatemeh
Krabisch, Petra
Just, Marianne
Augustin, Doris
Liedtke, Cornelia
Chao, Calvin
Shak, Steven
Wuerstlein, Rachel
Kreipe, Hans H.
Harbeck, Nadia
author_sort Nitz, Ulrike
collection PubMed
description BACKGROUND: The prospective phase 3 PlanB trial used the Oncotype DX(®) Recurrence Score(®) (RS) to define a genomically low-risk subset of clinically high-risk pN0-1 early breast cancer (EBC) patients for treatment with adjuvant endocrine therapy (ET) alone. Here, we report five-year data evaluating the prognostic value of RS, Ki-67, and other traditional clinicopathological parameters. METHODS: A central tumour bank was prospectively established within PlanB. Following an early amendment, hormone receptor (HR)+ , pN0-1 RS ≤ 11 patients were recommended to omit chemotherapy. Patients with RS ≥ 12, pN2-3, or HR-negative/HER2-negative disease were randomised to anthracycline-containing or anthracycline-free chemotherapy. Primary endpoint: disease-free survival (DFS). PlanB Clinicaltrials.gov identifier: NCT01049425. FINDINGS: From 2009 to 2011, PlanB enrolled 3198 patients (central tumour bank, n = 3073) with the median age of 56 years, 41.1% pN+, and 32.5% grade 3 EBC. Chemotherapy was omitted in 348/404 (86.1%) eligible RS ≤ 11 patients. After 55 months of median follow-up, five-year DFS in ET-treated RS ≤ 11 patients was 94% (in both pN0 and pN1) versus 94% (RS 12–25) and 84% (RS > 25) in chemotherapy-treated patients (p < 0.001); five-year overall survival (OS) was 99 versus 97% and 93%, respectively (p < 0.001). Nodal status, central/local grade, tumour size, continuous Ki-67, progesterone receptor (PR), IHC4, and RS were univariate prognostic factors for DFS. In a multivariate analysis including all univariate prognostic markers, only pN2-3, central and local grade 3, tumour size >2 cm, and RS, but not IHC4 or Ki-67 were independent adverse factors. If RS was excluded, IHC4 or both Ki-67 and PR entered the model. The impact of RS was particularly pronounced in patients with intermediate Ki-67 (>10%, <40%) tumours. INTERPRETATION: The excellent five-year outcomes in clinically high-risk, genomically low-risk (RS ≤ 11) pN0-1 patients without adjuvant chemotherapy support using RS with standardised pathology for treatment decisions in HR+ HER2-negative EBC. Ki-67 has the potential to support patient selection for genomic testing.
format Online
Article
Text
id pubmed-6336763
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Springer US
record_format MEDLINE/PubMed
spelling pubmed-63367632019-02-06 Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial Nitz, Ulrike Gluz, Oleg Christgen, Matthias Kates, Ronald E. Clemens, Michael Malter, Wolfram Nuding, Benno Aktas, Bahriye Kuemmel, Sherko Reimer, Toralf Stefek, Andrea Lorenz-Salehi, Fatemeh Krabisch, Petra Just, Marianne Augustin, Doris Liedtke, Cornelia Chao, Calvin Shak, Steven Wuerstlein, Rachel Kreipe, Hans H. Harbeck, Nadia Breast Cancer Res Treat Clinical Trial BACKGROUND: The prospective phase 3 PlanB trial used the Oncotype DX(®) Recurrence Score(®) (RS) to define a genomically low-risk subset of clinically high-risk pN0-1 early breast cancer (EBC) patients for treatment with adjuvant endocrine therapy (ET) alone. Here, we report five-year data evaluating the prognostic value of RS, Ki-67, and other traditional clinicopathological parameters. METHODS: A central tumour bank was prospectively established within PlanB. Following an early amendment, hormone receptor (HR)+ , pN0-1 RS ≤ 11 patients were recommended to omit chemotherapy. Patients with RS ≥ 12, pN2-3, or HR-negative/HER2-negative disease were randomised to anthracycline-containing or anthracycline-free chemotherapy. Primary endpoint: disease-free survival (DFS). PlanB Clinicaltrials.gov identifier: NCT01049425. FINDINGS: From 2009 to 2011, PlanB enrolled 3198 patients (central tumour bank, n = 3073) with the median age of 56 years, 41.1% pN+, and 32.5% grade 3 EBC. Chemotherapy was omitted in 348/404 (86.1%) eligible RS ≤ 11 patients. After 55 months of median follow-up, five-year DFS in ET-treated RS ≤ 11 patients was 94% (in both pN0 and pN1) versus 94% (RS 12–25) and 84% (RS > 25) in chemotherapy-treated patients (p < 0.001); five-year overall survival (OS) was 99 versus 97% and 93%, respectively (p < 0.001). Nodal status, central/local grade, tumour size, continuous Ki-67, progesterone receptor (PR), IHC4, and RS were univariate prognostic factors for DFS. In a multivariate analysis including all univariate prognostic markers, only pN2-3, central and local grade 3, tumour size >2 cm, and RS, but not IHC4 or Ki-67 were independent adverse factors. If RS was excluded, IHC4 or both Ki-67 and PR entered the model. The impact of RS was particularly pronounced in patients with intermediate Ki-67 (>10%, <40%) tumours. INTERPRETATION: The excellent five-year outcomes in clinically high-risk, genomically low-risk (RS ≤ 11) pN0-1 patients without adjuvant chemotherapy support using RS with standardised pathology for treatment decisions in HR+ HER2-negative EBC. Ki-67 has the potential to support patient selection for genomic testing. Springer US 2017-06-29 2017 /pmc/articles/PMC6336763/ /pubmed/28664507 http://dx.doi.org/10.1007/s10549-017-4358-6 Text en © The Author(s) 2017, corrected publication 2019 This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, a link is provided to the Creative Commons license and any changes made are indicated.
spellingShingle Clinical Trial
Nitz, Ulrike
Gluz, Oleg
Christgen, Matthias
Kates, Ronald E.
Clemens, Michael
Malter, Wolfram
Nuding, Benno
Aktas, Bahriye
Kuemmel, Sherko
Reimer, Toralf
Stefek, Andrea
Lorenz-Salehi, Fatemeh
Krabisch, Petra
Just, Marianne
Augustin, Doris
Liedtke, Cornelia
Chao, Calvin
Shak, Steven
Wuerstlein, Rachel
Kreipe, Hans H.
Harbeck, Nadia
Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial
title Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial
title_full Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial
title_fullStr Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial
title_full_unstemmed Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial
title_short Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial
title_sort reducing chemotherapy use in clinically high-risk, genomically low-risk pn0 and pn1 early breast cancer patients: five-year data from the prospective, randomised phase 3 west german study group (wsg) planb trial
topic Clinical Trial
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336763/
https://www.ncbi.nlm.nih.gov/pubmed/28664507
http://dx.doi.org/10.1007/s10549-017-4358-6
work_keys_str_mv AT nitzulrike reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT gluzoleg reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT christgenmatthias reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT katesronalde reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT clemensmichael reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT malterwolfram reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT nudingbenno reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT aktasbahriye reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT kuemmelsherko reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT reimertoralf reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT stefekandrea reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT lorenzsalehifatemeh reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT krabischpetra reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT justmarianne reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT augustindoris reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT liedtkecornelia reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT chaocalvin reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT shaksteven reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT wuerstleinrachel reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT kreipehansh reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial
AT harbecknadia reducingchemotherapyuseinclinicallyhighriskgenomicallylowriskpn0andpn1earlybreastcancerpatientsfiveyeardatafromtheprospectiverandomisedphase3westgermanstudygroupwsgplanbtrial