Morganti Stefania, Khan Rabia A, Berrocal-Almanza Luis C, Miranda Miguel, Luo Linlin, Xu Xiaoqing, Partridge Ann H, Lynce Filipa
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Oncology Outcomes Research, AstraZeneca, Cambridge, UK.
Oncol Ther. 2025 Apr 15. doi: 10.1007/s40487-025-00332-8.
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.
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.
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.
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.
Oncotype DX（ODX）复发评分（RS）可用于预测激素受体（HR）阳性/人表皮生长因子受体2（HER2）阴性早期乳腺癌患者的预后及化疗获益情况。关于按RS分层的种系BRCA1和/或BRCA2致病变异（gBRCA PV）分布的数据有限。这项回顾性的真实世界研究探讨了HR阳性/HER2阴性I-III期乳腺癌患者的人口统计学特征、临床特征、gBRCA检测率和gBRCA PV患病率，并按RS进行分层。
使用来自全国数据库中美国电子健康记录的去识别化患者数据（2011年1月1日至2022年9月30日）。纳入年龄≥18岁、患有HR阳性/HER2阴性乳腺癌且已知ODX RS的患者。比较低、中、高肿瘤RS患者的人口统计学特征、临床特征和基因检测率。对接受基因检测的患者按类别比较gBRCA PV患病率。
在3637例患者（中位年龄：62岁）中，950例（26.1%）肿瘤RS低，2155例（59.3%）肿瘤RS中等，532例（14.6%）肿瘤RS高。尽管随着时间推移基因检测有所增加，但仅31.5%（n = 1147/3637）的患者确定了gBRCA状态。在接受检测的患者中，37/1147（3.2%）有gBRCA PV；gBRCA PV携带者的中位年龄低于非携带者（52岁对56岁；p = 0.034）；gBRCA PV携带者的肿瘤分级（p = 0.002）和中位RS（p = 0.001）显著高于非携带者；gBRCA PV患病率在肿瘤RS高的检测患者中最高（n = 14/185；7.6%），但在肿瘤RS中等（n = 19/674；2.8%）和低（n = 4/288；1.4%）的患者中也发现了gBRCA PV。
gBRCA PV患病率在肿瘤RS高的患者中最高，但在肿瘤RS中等和低的患者中也不容忽视。无论ODX RS如何，更广泛地开展基因检测有助于优化HR阳性/HER2阴性早期乳腺癌患者的管理。
