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Breast Cancer Index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the Adjuvant Tamoxifen—To Offer More? (aTTom) trial

BACKGROUND: Extending the duration of adjuvant endocrine therapy reduces the risk of recurrence in a subset of women with early-stage hormone receptor-positive (HR+) breast cancer. Validated predictive biomarkers of endocrine response could significantly improve patient selection for extended therap...

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Autores principales: Bartlett, J M S, Sgroi, D C, Treuner, K, Zhang, Y, Ahmed, I, Piper, T, Salunga, R, Brachtel, E F, Pirrie, S J, Schnabel, C A, Rea, D W
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927322/
https://www.ncbi.nlm.nih.gov/pubmed/31504126
http://dx.doi.org/10.1093/annonc/mdz289
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author Bartlett, J M S
Sgroi, D C
Treuner, K
Zhang, Y
Ahmed, I
Piper, T
Salunga, R
Brachtel, E F
Pirrie, S J
Schnabel, C A
Rea, D W
author_facet Bartlett, J M S
Sgroi, D C
Treuner, K
Zhang, Y
Ahmed, I
Piper, T
Salunga, R
Brachtel, E F
Pirrie, S J
Schnabel, C A
Rea, D W
author_sort Bartlett, J M S
collection PubMed
description BACKGROUND: Extending the duration of adjuvant endocrine therapy reduces the risk of recurrence in a subset of women with early-stage hormone receptor-positive (HR+) breast cancer. Validated predictive biomarkers of endocrine response could significantly improve patient selection for extended therapy. Breast cancer index (BCI) [HOXB13/IL17BR ratio (H/I)] was evaluated for its ability to predict benefit from extended endocrine therapy in patients previously randomized in the Adjuvant Tamoxifen—To Offer More? (aTTom) trial. PATIENTS AND METHODS: Trans-aTTom is a multi-institutional, prospective–retrospective study in patients with available formalin-fixed paraffin-embedded primary tumor blocks. BCI testing and central determination of estrogen receptor (ER) and progesterone receptor (PR) status by immunohistochemistry were carried out blinded to clinical outcome. Survival endpoints were evaluated using Kaplan–Meier analysis and Cox regression with recurrence-free interval (RFI) as the primary endpoint. Interaction between extended endocrine therapy and BCI (H/I) was assessed using the likelihood ratio test. RESULTS: Of 583 HR+, N+ patients analyzed, 49% classified as BCI (H/I)-High derived a significant benefit from 10 versus 5 years of tamoxifen treatment [hazard ratio (HR): 0.35; 95% confidence interval (CI) 0.15–0.86; 10.2% absolute risk reduction based on RFI, P = 0.027]. BCI (H/I)-low patients showed no significant benefit from extended endocrine therapy (HR: 1.07; 95% CI 0.69–1.65; −0.2% absolute risk reduction; P = 0.768). Continuous BCI (H/I) levels predicted the magnitude of benefit from extended tamoxifen, whereas centralized ER and PR did not. Interaction between extended tamoxifen treatment and BCI (H/I) was statistically significant (P = 0.012), adjusting for clinicopathological factors. CONCLUSION: BCI by high H/I expression was predictive of endocrine response and identified a subset of HR+, N+ patients with significant benefit from 10 versus 5 years of tamoxifen therapy. These data provide further validation, consistent with previous MA.17 data, establishing level 1B evidence for BCI as a predictive biomarker of benefit from extended endocrine therapy. TRIAL REGISTRATION: ISRCTN17222211; NCT00003678.
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spelling pubmed-69273222019-12-27 Breast Cancer Index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the Adjuvant Tamoxifen—To Offer More? (aTTom) trial Bartlett, J M S Sgroi, D C Treuner, K Zhang, Y Ahmed, I Piper, T Salunga, R Brachtel, E F Pirrie, S J Schnabel, C A Rea, D W Ann Oncol Original Articles BACKGROUND: Extending the duration of adjuvant endocrine therapy reduces the risk of recurrence in a subset of women with early-stage hormone receptor-positive (HR+) breast cancer. Validated predictive biomarkers of endocrine response could significantly improve patient selection for extended therapy. Breast cancer index (BCI) [HOXB13/IL17BR ratio (H/I)] was evaluated for its ability to predict benefit from extended endocrine therapy in patients previously randomized in the Adjuvant Tamoxifen—To Offer More? (aTTom) trial. PATIENTS AND METHODS: Trans-aTTom is a multi-institutional, prospective–retrospective study in patients with available formalin-fixed paraffin-embedded primary tumor blocks. BCI testing and central determination of estrogen receptor (ER) and progesterone receptor (PR) status by immunohistochemistry were carried out blinded to clinical outcome. Survival endpoints were evaluated using Kaplan–Meier analysis and Cox regression with recurrence-free interval (RFI) as the primary endpoint. Interaction between extended endocrine therapy and BCI (H/I) was assessed using the likelihood ratio test. RESULTS: Of 583 HR+, N+ patients analyzed, 49% classified as BCI (H/I)-High derived a significant benefit from 10 versus 5 years of tamoxifen treatment [hazard ratio (HR): 0.35; 95% confidence interval (CI) 0.15–0.86; 10.2% absolute risk reduction based on RFI, P = 0.027]. BCI (H/I)-low patients showed no significant benefit from extended endocrine therapy (HR: 1.07; 95% CI 0.69–1.65; −0.2% absolute risk reduction; P = 0.768). Continuous BCI (H/I) levels predicted the magnitude of benefit from extended tamoxifen, whereas centralized ER and PR did not. Interaction between extended tamoxifen treatment and BCI (H/I) was statistically significant (P = 0.012), adjusting for clinicopathological factors. CONCLUSION: BCI by high H/I expression was predictive of endocrine response and identified a subset of HR+, N+ patients with significant benefit from 10 versus 5 years of tamoxifen therapy. These data provide further validation, consistent with previous MA.17 data, establishing level 1B evidence for BCI as a predictive biomarker of benefit from extended endocrine therapy. TRIAL REGISTRATION: ISRCTN17222211; NCT00003678. Oxford University Press 2019-11 2019-08-28 /pmc/articles/PMC6927322/ /pubmed/31504126 http://dx.doi.org/10.1093/annonc/mdz289 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Articles
Bartlett, J M S
Sgroi, D C
Treuner, K
Zhang, Y
Ahmed, I
Piper, T
Salunga, R
Brachtel, E F
Pirrie, S J
Schnabel, C A
Rea, D W
Breast Cancer Index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the Adjuvant Tamoxifen—To Offer More? (aTTom) trial
title Breast Cancer Index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the Adjuvant Tamoxifen—To Offer More? (aTTom) trial
title_full Breast Cancer Index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the Adjuvant Tamoxifen—To Offer More? (aTTom) trial
title_fullStr Breast Cancer Index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the Adjuvant Tamoxifen—To Offer More? (aTTom) trial
title_full_unstemmed Breast Cancer Index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the Adjuvant Tamoxifen—To Offer More? (aTTom) trial
title_short Breast Cancer Index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the Adjuvant Tamoxifen—To Offer More? (aTTom) trial
title_sort breast cancer index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the adjuvant tamoxifen—to offer more? (attom) trial
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927322/
https://www.ncbi.nlm.nih.gov/pubmed/31504126
http://dx.doi.org/10.1093/annonc/mdz289
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