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21-Gene assay as predictor of chemotherapy benefit in HER2-negative breast cancer
The NSABP B-20 prospective-retrospective study of the 21-gene Oncotype DX Breast Cancer Recurrence Score® test predicted benefit from addition of chemotherapy to tamoxifen in node-negative, estrogen-receptor positive breast cancer when recurrence score (RS) was ≥31. HER2 is a component of the RS alg...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235896/ https://www.ncbi.nlm.nih.gov/pubmed/30456299 http://dx.doi.org/10.1038/s41523-018-0090-6 |
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author | Geyer, Charles E. Tang, Gong Mamounas, Eleftherios P. Rastogi, Priya Paik, Soonmyung Shak, Steven Baehner, Frederick L. Crager, Michael Wickerham, D. Lawrence Costantino, Joseph P. Wolmark, Norman |
author_facet | Geyer, Charles E. Tang, Gong Mamounas, Eleftherios P. Rastogi, Priya Paik, Soonmyung Shak, Steven Baehner, Frederick L. Crager, Michael Wickerham, D. Lawrence Costantino, Joseph P. Wolmark, Norman |
author_sort | Geyer, Charles E. |
collection | PubMed |
description | The NSABP B-20 prospective-retrospective study of the 21-gene Oncotype DX Breast Cancer Recurrence Score® test predicted benefit from addition of chemotherapy to tamoxifen in node-negative, estrogen-receptor positive breast cancer when recurrence score (RS) was ≥31. HER2 is a component of the RS algorithm with a positive coefficient and contributes to higher RS values. Accrual to B-20 occurred prior to routine testing for HER2, so questions have arisen regarding assay performance if HER2-positive patients were identified and excluded. We report an exploratory reanalysis of the B-20, 21-gene study following exclusion of such patients. Patients were considered HER2 positive if quantitative RT-PCR for HER2 was ≥11.5 units, and excluded from re-analyses performed using the original cutoffs: <18, 18–30, ≥31, and the TAILORx cutoffs: <11, 11–25, >25. The endpoint remained distant recurrence-free interval (DRFI) as in the original study. Distribution was estimated via the Kaplan–Meier method and compared via log-rank test. Multivariate Cox proportional hazards models estimated chemotherapy benefit in each group. In the RS < 18 and 18–30 groups, 1.7 and 6.7% were HER2 positive. In the RS ≥ 31 group, 41% were HER2 positive. Exclusion resulted in fewer events, with loss of significance for benefit from chemotherapy in the overall HER2-negative cohort (log-rank P = 0.06), but substantial benefit from chemotherapy remained in the RS ≥ 31 cohort (HR = 0.18; 95% CI: 0.07–0.47) and the RS > 25 cohort (HR = 0.28; 95% CI: 0.12–0.64). No benefit from chemotherapy was evident in the other RS groups. Following exclusion of HER2-positive patients based on RT-PCR expression, substantial benefit of chemotherapy remained for RS ≥ 31 as originally employed, and with RS > 25 employed in TAILORx. |
format | Online Article Text |
id | pubmed-6235896 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-62358962018-11-19 21-Gene assay as predictor of chemotherapy benefit in HER2-negative breast cancer Geyer, Charles E. Tang, Gong Mamounas, Eleftherios P. Rastogi, Priya Paik, Soonmyung Shak, Steven Baehner, Frederick L. Crager, Michael Wickerham, D. Lawrence Costantino, Joseph P. Wolmark, Norman NPJ Breast Cancer Article The NSABP B-20 prospective-retrospective study of the 21-gene Oncotype DX Breast Cancer Recurrence Score® test predicted benefit from addition of chemotherapy to tamoxifen in node-negative, estrogen-receptor positive breast cancer when recurrence score (RS) was ≥31. HER2 is a component of the RS algorithm with a positive coefficient and contributes to higher RS values. Accrual to B-20 occurred prior to routine testing for HER2, so questions have arisen regarding assay performance if HER2-positive patients were identified and excluded. We report an exploratory reanalysis of the B-20, 21-gene study following exclusion of such patients. Patients were considered HER2 positive if quantitative RT-PCR for HER2 was ≥11.5 units, and excluded from re-analyses performed using the original cutoffs: <18, 18–30, ≥31, and the TAILORx cutoffs: <11, 11–25, >25. The endpoint remained distant recurrence-free interval (DRFI) as in the original study. Distribution was estimated via the Kaplan–Meier method and compared via log-rank test. Multivariate Cox proportional hazards models estimated chemotherapy benefit in each group. In the RS < 18 and 18–30 groups, 1.7 and 6.7% were HER2 positive. In the RS ≥ 31 group, 41% were HER2 positive. Exclusion resulted in fewer events, with loss of significance for benefit from chemotherapy in the overall HER2-negative cohort (log-rank P = 0.06), but substantial benefit from chemotherapy remained in the RS ≥ 31 cohort (HR = 0.18; 95% CI: 0.07–0.47) and the RS > 25 cohort (HR = 0.28; 95% CI: 0.12–0.64). No benefit from chemotherapy was evident in the other RS groups. Following exclusion of HER2-positive patients based on RT-PCR expression, substantial benefit of chemotherapy remained for RS ≥ 31 as originally employed, and with RS > 25 employed in TAILORx. Nature Publishing Group UK 2018-11-14 /pmc/articles/PMC6235896/ /pubmed/30456299 http://dx.doi.org/10.1038/s41523-018-0090-6 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Geyer, Charles E. Tang, Gong Mamounas, Eleftherios P. Rastogi, Priya Paik, Soonmyung Shak, Steven Baehner, Frederick L. Crager, Michael Wickerham, D. Lawrence Costantino, Joseph P. Wolmark, Norman 21-Gene assay as predictor of chemotherapy benefit in HER2-negative breast cancer |
title | 21-Gene assay as predictor of chemotherapy benefit in HER2-negative breast cancer |
title_full | 21-Gene assay as predictor of chemotherapy benefit in HER2-negative breast cancer |
title_fullStr | 21-Gene assay as predictor of chemotherapy benefit in HER2-negative breast cancer |
title_full_unstemmed | 21-Gene assay as predictor of chemotherapy benefit in HER2-negative breast cancer |
title_short | 21-Gene assay as predictor of chemotherapy benefit in HER2-negative breast cancer |
title_sort | 21-gene assay as predictor of chemotherapy benefit in her2-negative breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235896/ https://www.ncbi.nlm.nih.gov/pubmed/30456299 http://dx.doi.org/10.1038/s41523-018-0090-6 |
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