Oncotype DX Recurrence Score and Germline BRCA Variants in Patients with HR-Positive/HER2-Negative Early Breast Cancer: A Retrospective Observational Study

Abstract Introduction The Oncotype DX (ODX) recurrence score (RS) is prognostic and predictive of chemotherapy benefit in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. Data on the distribution of germline BRCA1 and/or BRCA2...

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Main Authors: Stefania Morganti, Rabia A. Khan, Luis C. Berrocal-Almanza, Miguel Miranda, Linlin Luo, Xiaoqing Xu, Ann H. Partridge, Filipa Lynce
Format: Article
Language:English
Published: Adis, Springer Healthcare 2025-04-01
Series:Oncology and Therapy
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Online Access:https://doi.org/10.1007/s40487-025-00332-8
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author Stefania Morganti
Rabia A. Khan
Luis C. Berrocal-Almanza
Miguel Miranda
Linlin Luo
Xiaoqing Xu
Ann H. Partridge
Filipa Lynce
author_facet Stefania Morganti
Rabia A. Khan
Luis C. Berrocal-Almanza
Miguel Miranda
Linlin Luo
Xiaoqing Xu
Ann H. Partridge
Filipa Lynce
author_sort Stefania Morganti
collection DOAJ
description Abstract Introduction The Oncotype DX (ODX) recurrence score (RS) is prognostic and predictive of chemotherapy benefit in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. Data on the distribution of germline BRCA1 and/or BRCA2 pathogenic variants (gBRCA PV) by RS are limited. This retrospective, real-world study explored demographics, clinical characteristics, gBRCA testing rates, and gBRCA PV prevalence in HR-positive/HER2-negative stage I–III breast cancer, stratified by RS. Methods Deidentified patient data (from 1 January 2011 to 30 September 2022) from US electronic health records in a nationwide database were used. Patients aged ≥ 18 years with HR-positive/HER2-negative breast cancer and a known ODX RS were included. Demographics, clinical characteristics, and genetic testing rates were compared in patients with low, intermediate, and high tumor RS. gBRCA PV prevalence was compared across categories in patients who underwent genetic testing. Results Of 3637 patients (median age: 62 years), 950 (26.1%) had low, 2155 (59.3%) had intermediate, and 532 (14.6%) had high tumor RS. Despite increases in genetic testing over time, gBRCA status was determined in only 31.5% (n = 1147/3637) of patients. Among tested patients, 37/1147 (3.2%) had gBRCA PV; median age was lower in gBRCA PV carriers than in noncarriers (52 versus 56 years; p = 0.034); tumors from gBRCA PV carriers had significantly higher grade (p = 0.002) and median RS (p = 0.001) than tumors from noncarriers; prevalence of gBRCA PV was highest among tested patients with high tumor RS (n = 14/185; 7.6%), but gBRCA PVs were identified among patients with intermediate (n = 19/674; 2.8%) and low (n = 4/288; 1.4%) tumor RS. Conclusions Prevalence of gBRCA PV was highest among patients with high tumor RS, but not negligible in patients with intermediate and low tumor RS. Wider implementation of genetic testing, irrespective of ODX RS, could help optimize the management of patients with HR-positive/HER2-negative early breast cancer. Graphical Abstract
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spelling doaj-art-3161a53a11894ab883acdf66487026cd2025-08-20T03:10:27ZengAdis, Springer HealthcareOncology and Therapy2366-10702366-10892025-04-0113236337910.1007/s40487-025-00332-8Oncotype DX Recurrence Score and Germline BRCA Variants in Patients with HR-Positive/HER2-Negative Early Breast Cancer: A Retrospective Observational StudyStefania Morganti0Rabia A. Khan1Luis C. Berrocal-Almanza2Miguel Miranda3Linlin Luo4Xiaoqing Xu5Ann H. Partridge6Filipa Lynce7Dana-Farber Cancer Institute, Harvard Medical SchoolOncology Outcomes Research, AstraZenecaOncology Outcomes Research, AstraZenecaOncology Outcomes Research, AstraZenecaOncology Outcomes Research, AstraZenecaOncology Outcomes Research, AstraZenecaDana-Farber Cancer Institute, Harvard Medical SchoolDana-Farber Cancer Institute, Harvard Medical SchoolAbstract Introduction The Oncotype DX (ODX) recurrence score (RS) is prognostic and predictive of chemotherapy benefit in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. Data on the distribution of germline BRCA1 and/or BRCA2 pathogenic variants (gBRCA PV) by RS are limited. This retrospective, real-world study explored demographics, clinical characteristics, gBRCA testing rates, and gBRCA PV prevalence in HR-positive/HER2-negative stage I–III breast cancer, stratified by RS. Methods Deidentified patient data (from 1 January 2011 to 30 September 2022) from US electronic health records in a nationwide database were used. Patients aged ≥ 18 years with HR-positive/HER2-negative breast cancer and a known ODX RS were included. Demographics, clinical characteristics, and genetic testing rates were compared in patients with low, intermediate, and high tumor RS. gBRCA PV prevalence was compared across categories in patients who underwent genetic testing. Results Of 3637 patients (median age: 62 years), 950 (26.1%) had low, 2155 (59.3%) had intermediate, and 532 (14.6%) had high tumor RS. Despite increases in genetic testing over time, gBRCA status was determined in only 31.5% (n = 1147/3637) of patients. Among tested patients, 37/1147 (3.2%) had gBRCA PV; median age was lower in gBRCA PV carriers than in noncarriers (52 versus 56 years; p = 0.034); tumors from gBRCA PV carriers had significantly higher grade (p = 0.002) and median RS (p = 0.001) than tumors from noncarriers; prevalence of gBRCA PV was highest among tested patients with high tumor RS (n = 14/185; 7.6%), but gBRCA PVs were identified among patients with intermediate (n = 19/674; 2.8%) and low (n = 4/288; 1.4%) tumor RS. Conclusions Prevalence of gBRCA PV was highest among patients with high tumor RS, but not negligible in patients with intermediate and low tumor RS. Wider implementation of genetic testing, irrespective of ODX RS, could help optimize the management of patients with HR-positive/HER2-negative early breast cancer. Graphical Abstracthttps://doi.org/10.1007/s40487-025-00332-8BRCA1/BRCA2 geneBRCA testingEarly breast cancerGenetic testingGermline BRCA pathogenic variantsGermline BRCA variant HR-positive
spellingShingle Stefania Morganti
Rabia A. Khan
Luis C. Berrocal-Almanza
Miguel Miranda
Linlin Luo
Xiaoqing Xu
Ann H. Partridge
Filipa Lynce
Oncotype DX Recurrence Score and Germline BRCA Variants in Patients with HR-Positive/HER2-Negative Early Breast Cancer: A Retrospective Observational Study
Oncology and Therapy
BRCA1/BRCA2 gene
BRCA testing
Early breast cancer
Genetic testing
Germline BRCA pathogenic variants
Germline BRCA variant HR-positive
title Oncotype DX Recurrence Score and Germline BRCA Variants in Patients with HR-Positive/HER2-Negative Early Breast Cancer: A Retrospective Observational Study
title_full Oncotype DX Recurrence Score and Germline BRCA Variants in Patients with HR-Positive/HER2-Negative Early Breast Cancer: A Retrospective Observational Study
title_fullStr Oncotype DX Recurrence Score and Germline BRCA Variants in Patients with HR-Positive/HER2-Negative Early Breast Cancer: A Retrospective Observational Study
title_full_unstemmed Oncotype DX Recurrence Score and Germline BRCA Variants in Patients with HR-Positive/HER2-Negative Early Breast Cancer: A Retrospective Observational Study
title_short Oncotype DX Recurrence Score and Germline BRCA Variants in Patients with HR-Positive/HER2-Negative Early Breast Cancer: A Retrospective Observational Study
title_sort oncotype dx recurrence score and germline brca variants in patients with hr positive her2 negative early breast cancer a retrospective observational study
topic BRCA1/BRCA2 gene
BRCA testing
Early breast cancer
Genetic testing
Germline BRCA pathogenic variants
Germline BRCA variant HR-positive
url https://doi.org/10.1007/s40487-025-00332-8
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