Siddhartha Yadav, Fergus J Couch, Sam Hillman, Linlin Luo, Weiyan Li, Qixin Li, Jennifer Fallas Hayes, Jagadeswara R Earla, Xiaoqing Xu
{"title":"真实世界种系BRCA检测、聚（adp -核糖）聚合酶抑制剂的使用和人类表皮生长因子受体2阴性转移性乳腺癌的生存结果","authors":"Siddhartha Yadav, Fergus J Couch, Sam Hillman, Linlin Luo, Weiyan Li, Qixin Li, Jennifer Fallas Hayes, Jagadeswara R Earla, Xiaoqing Xu","doi":"10.1200/PO-24-00814","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Testing for germline <i>BRCA1</i> and/or <i>BRCA2</i> mutations (gBRCAm) is recommended for patients with human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) to guide treatment selection with poly (ADP-ribose) polymerase inhibitors (PARPis). However, real-world data on germline <i>BRCA1</i> and/or <i>BRCA2</i> (gBRCA) testing and PARPi treatment patterns in metastatic BC (mBC) are limited.</p><p><strong>Methods: </strong>Deidentified patient data from adults diagnosed with HER2- mBC between 2014 and 2022 were captured from electronic health records in the US Flatiron Health database. gBRCA testing patterns and prevalence were examined by tumor subtype (hormone receptor-positive [HR+]/triple-negative) and disease stage at diagnosis. Demographic and clinical characteristics were described by receipt of gBRCA testing and PARPi. PARPi treatment patterns were assessed, and real-word overall survival (OS) was estimated in patients with gBRCAm diagnosed with mBC after January 1, 2018.</p><p><strong>Results: </strong>Of the 15,006 total patients, 4,654 (31.0%) received a gBRCA test. gBRCA testing rates mostly increased from 2014 to 2022 and were lower in patients with HR+ than triple-negative tumors. Of the patients who underwent gBRCA testing, 337 (7.2%) had gBRCAm. From 2018 to 2022, PARPi was initiated in 94 (45.6%) of 206 patients with gBRCAm. With a median follow-up of 22.8 months across patients with available first-line treatment start dates, real-world OS was numerically longer among 94 patients with gBRCAm who received PARPi (32.3 months [95% CI, 22.7 to 47.4]) than among 99 patients who did not (21.9 months [95% CI, 18.4 to not reached]).</p><p><strong>Conclusion: </strong>Although gBRCA testing increased over time, testing and PARPi utilization rates remained suboptimal in potentially eligible patients with HER2- mBC. Exploratory analysis showed numerically longer OS in patients who received PARPi. Wider and timelier gBRCA testing is warranted to inform potentially optimal treatment decisions.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400814"},"PeriodicalIF":5.6000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278751/pdf/","citationCount":"0","resultStr":"{\"title\":\"Real-World Germline BRCA Testing, Poly(ADP-ribose) Polymerase Inhibitor Utilization, and Survival Outcomes in Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer.\",\"authors\":\"Siddhartha Yadav, Fergus J Couch, Sam Hillman, Linlin Luo, Weiyan Li, Qixin Li, Jennifer Fallas Hayes, Jagadeswara R Earla, Xiaoqing Xu\",\"doi\":\"10.1200/PO-24-00814\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Testing for germline <i>BRCA1</i> and/or <i>BRCA2</i> mutations (gBRCAm) is recommended for patients with human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) to guide treatment selection with poly (ADP-ribose) polymerase inhibitors (PARPis). However, real-world data on germline <i>BRCA1</i> and/or <i>BRCA2</i> (gBRCA) testing and PARPi treatment patterns in metastatic BC (mBC) are limited.</p><p><strong>Methods: </strong>Deidentified patient data from adults diagnosed with HER2- mBC between 2014 and 2022 were captured from electronic health records in the US Flatiron Health database. gBRCA testing patterns and prevalence were examined by tumor subtype (hormone receptor-positive [HR+]/triple-negative) and disease stage at diagnosis. Demographic and clinical characteristics were described by receipt of gBRCA testing and PARPi. PARPi treatment patterns were assessed, and real-word overall survival (OS) was estimated in patients with gBRCAm diagnosed with mBC after January 1, 2018.</p><p><strong>Results: </strong>Of the 15,006 total patients, 4,654 (31.0%) received a gBRCA test. gBRCA testing rates mostly increased from 2014 to 2022 and were lower in patients with HR+ than triple-negative tumors. Of the patients who underwent gBRCA testing, 337 (7.2%) had gBRCAm. From 2018 to 2022, PARPi was initiated in 94 (45.6%) of 206 patients with gBRCAm. With a median follow-up of 22.8 months across patients with available first-line treatment start dates, real-world OS was numerically longer among 94 patients with gBRCAm who received PARPi (32.3 months [95% CI, 22.7 to 47.4]) than among 99 patients who did not (21.9 months [95% CI, 18.4 to not reached]).</p><p><strong>Conclusion: </strong>Although gBRCA testing increased over time, testing and PARPi utilization rates remained suboptimal in potentially eligible patients with HER2- mBC. Exploratory analysis showed numerically longer OS in patients who received PARPi. Wider and timelier gBRCA testing is warranted to inform potentially optimal treatment decisions.</p>\",\"PeriodicalId\":14797,\"journal\":{\"name\":\"JCO precision oncology\",\"volume\":\"9 \",\"pages\":\"e2400814\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278751/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JCO precision oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/PO-24-00814\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/7/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JCO precision oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/PO-24-00814","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/16 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Real-World Germline BRCA Testing, Poly(ADP-ribose) Polymerase Inhibitor Utilization, and Survival Outcomes in Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer.
Purpose: Testing for germline BRCA1 and/or BRCA2 mutations (gBRCAm) is recommended for patients with human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) to guide treatment selection with poly (ADP-ribose) polymerase inhibitors (PARPis). However, real-world data on germline BRCA1 and/or BRCA2 (gBRCA) testing and PARPi treatment patterns in metastatic BC (mBC) are limited.
Methods: Deidentified patient data from adults diagnosed with HER2- mBC between 2014 and 2022 were captured from electronic health records in the US Flatiron Health database. gBRCA testing patterns and prevalence were examined by tumor subtype (hormone receptor-positive [HR+]/triple-negative) and disease stage at diagnosis. Demographic and clinical characteristics were described by receipt of gBRCA testing and PARPi. PARPi treatment patterns were assessed, and real-word overall survival (OS) was estimated in patients with gBRCAm diagnosed with mBC after January 1, 2018.
Results: Of the 15,006 total patients, 4,654 (31.0%) received a gBRCA test. gBRCA testing rates mostly increased from 2014 to 2022 and were lower in patients with HR+ than triple-negative tumors. Of the patients who underwent gBRCA testing, 337 (7.2%) had gBRCAm. From 2018 to 2022, PARPi was initiated in 94 (45.6%) of 206 patients with gBRCAm. With a median follow-up of 22.8 months across patients with available first-line treatment start dates, real-world OS was numerically longer among 94 patients with gBRCAm who received PARPi (32.3 months [95% CI, 22.7 to 47.4]) than among 99 patients who did not (21.9 months [95% CI, 18.4 to not reached]).
Conclusion: Although gBRCA testing increased over time, testing and PARPi utilization rates remained suboptimal in potentially eligible patients with HER2- mBC. Exploratory analysis showed numerically longer OS in patients who received PARPi. Wider and timelier gBRCA testing is warranted to inform potentially optimal treatment decisions.
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