Moumita Chaki, Mona Benrashid, Subir Puri, Smruthy Sivakumar, Ethan S Sokol, Josefa M Briceno, Neil Vasan
{"title":"回顾性比较乳腺癌组织和血液为基础的下一代测序结果检测PIK3CA， AKT1和PTEN的改变。","authors":"Moumita Chaki, Mona Benrashid, Subir Puri, Smruthy Sivakumar, Ethan S Sokol, Josefa M Briceno, Neil Vasan","doi":"10.1186/s13058-025-02055-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Based on the CAPItello-291 phase III trial results, capivasertib in combination with fulvestrant has been approved for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer harboring one or more PIK3CA, AKT1, and/or PTEN alterations. Given the growing interest in circulating tumor DNA (ctDNA) next-generation sequencing (NGS) to detect PIK3CA/AKT1/PTEN alterations, we retrospectively compared blood-based FoundationOne®Liquid CDx versus tumor tissue-based FoundationOne®CDx real-world data from patients with various breast cancer subtypes.</p><p><strong>Methods: </strong>We utilized a database of patients profiled with FoundationOne®CDx and/or FoundationOne®Liquid CDx during routine clinical care. Analytical comparison of all pathogenic alterations in PIK3CA, AKT1, AKT2, AKT3, and PTEN, including alterations defined in the CAPItello-291 protocol (CAPItello-defined alterations), was performed in paired data from 289 patients with both tissue and liquid biopsies sampled within 90 days of each other.</p><p><strong>Results: </strong>Overall positive percent agreement (PPA) for short variants across ctDNA tumor fraction (TF) subgroups in paired biopsy samples was: ctDNA TF ≥ 10%: PIK3CA, 93.9%; AKT1, 100%; PTEN, 100%; ctDNA TF 1%-10%: PIK3CA, 96.3%; AKT1, 100%; PTEN, 100%; ctDNA TF < 1%: PIK3CA, 34.7%; AKT1, 50.0%; PTEN, 37.5%. PPA for CAPItello-defined alterations was: ctDNA TF ≥ 10%: 92.5%; ctDNA TF 1%-10%: 97.1%; ctDNA TF < 1%: 33.9%. For PTEN homozygous deletions, PPA was 50.0% in cases with ctDNA TF ≥ 10%. Overall PPA for AKT2 and AKT3 copy number variations (CNVs) was 66.7% and 0%, respectively.</p><p><strong>Conclusions: </strong>Blood-based NGS could offer a minimally invasive option to identify clinically relevant PIK3CA/AKT1/PTEN short variants in cases with ctDNA TF ≥ 1%. Confirmatory tissue-based NGS should be performed when blood-based NGS results are negative, especially when ctDNA TF is < 1% and for enhanced detection of CNVs in general.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"122"},"PeriodicalIF":5.6000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12217283/pdf/","citationCount":"0","resultStr":"{\"title\":\"Retrospective comparison between breast cancer tissue- and blood-based next-generation sequencing results in detection of PIK3CA, AKT1, and PTEN alterations.\",\"authors\":\"Moumita Chaki, Mona Benrashid, Subir Puri, Smruthy Sivakumar, Ethan S Sokol, Josefa M Briceno, Neil Vasan\",\"doi\":\"10.1186/s13058-025-02055-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Based on the CAPItello-291 phase III trial results, capivasertib in combination with fulvestrant has been approved for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer harboring one or more PIK3CA, AKT1, and/or PTEN alterations. Given the growing interest in circulating tumor DNA (ctDNA) next-generation sequencing (NGS) to detect PIK3CA/AKT1/PTEN alterations, we retrospectively compared blood-based FoundationOne®Liquid CDx versus tumor tissue-based FoundationOne®CDx real-world data from patients with various breast cancer subtypes.</p><p><strong>Methods: </strong>We utilized a database of patients profiled with FoundationOne®CDx and/or FoundationOne®Liquid CDx during routine clinical care. Analytical comparison of all pathogenic alterations in PIK3CA, AKT1, AKT2, AKT3, and PTEN, including alterations defined in the CAPItello-291 protocol (CAPItello-defined alterations), was performed in paired data from 289 patients with both tissue and liquid biopsies sampled within 90 days of each other.</p><p><strong>Results: </strong>Overall positive percent agreement (PPA) for short variants across ctDNA tumor fraction (TF) subgroups in paired biopsy samples was: ctDNA TF ≥ 10%: PIK3CA, 93.9%; AKT1, 100%; PTEN, 100%; ctDNA TF 1%-10%: PIK3CA, 96.3%; AKT1, 100%; PTEN, 100%; ctDNA TF < 1%: PIK3CA, 34.7%; AKT1, 50.0%; PTEN, 37.5%. PPA for CAPItello-defined alterations was: ctDNA TF ≥ 10%: 92.5%; ctDNA TF 1%-10%: 97.1%; ctDNA TF < 1%: 33.9%. For PTEN homozygous deletions, PPA was 50.0% in cases with ctDNA TF ≥ 10%. Overall PPA for AKT2 and AKT3 copy number variations (CNVs) was 66.7% and 0%, respectively.</p><p><strong>Conclusions: </strong>Blood-based NGS could offer a minimally invasive option to identify clinically relevant PIK3CA/AKT1/PTEN short variants in cases with ctDNA TF ≥ 1%. Confirmatory tissue-based NGS should be performed when blood-based NGS results are negative, especially when ctDNA TF is < 1% and for enhanced detection of CNVs in general.</p>\",\"PeriodicalId\":49227,\"journal\":{\"name\":\"Breast Cancer Research\",\"volume\":\"27 1\",\"pages\":\"122\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12217283/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Breast Cancer Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13058-025-02055-0\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Breast Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13058-025-02055-0","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
Retrospective comparison between breast cancer tissue- and blood-based next-generation sequencing results in detection of PIK3CA, AKT1, and PTEN alterations.
Background: Based on the CAPItello-291 phase III trial results, capivasertib in combination with fulvestrant has been approved for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer harboring one or more PIK3CA, AKT1, and/or PTEN alterations. Given the growing interest in circulating tumor DNA (ctDNA) next-generation sequencing (NGS) to detect PIK3CA/AKT1/PTEN alterations, we retrospectively compared blood-based FoundationOne®Liquid CDx versus tumor tissue-based FoundationOne®CDx real-world data from patients with various breast cancer subtypes.
Methods: We utilized a database of patients profiled with FoundationOne®CDx and/or FoundationOne®Liquid CDx during routine clinical care. Analytical comparison of all pathogenic alterations in PIK3CA, AKT1, AKT2, AKT3, and PTEN, including alterations defined in the CAPItello-291 protocol (CAPItello-defined alterations), was performed in paired data from 289 patients with both tissue and liquid biopsies sampled within 90 days of each other.
Results: Overall positive percent agreement (PPA) for short variants across ctDNA tumor fraction (TF) subgroups in paired biopsy samples was: ctDNA TF ≥ 10%: PIK3CA, 93.9%; AKT1, 100%; PTEN, 100%; ctDNA TF 1%-10%: PIK3CA, 96.3%; AKT1, 100%; PTEN, 100%; ctDNA TF < 1%: PIK3CA, 34.7%; AKT1, 50.0%; PTEN, 37.5%. PPA for CAPItello-defined alterations was: ctDNA TF ≥ 10%: 92.5%; ctDNA TF 1%-10%: 97.1%; ctDNA TF < 1%: 33.9%. For PTEN homozygous deletions, PPA was 50.0% in cases with ctDNA TF ≥ 10%. Overall PPA for AKT2 and AKT3 copy number variations (CNVs) was 66.7% and 0%, respectively.
Conclusions: Blood-based NGS could offer a minimally invasive option to identify clinically relevant PIK3CA/AKT1/PTEN short variants in cases with ctDNA TF ≥ 1%. Confirmatory tissue-based NGS should be performed when blood-based NGS results are negative, especially when ctDNA TF is < 1% and for enhanced detection of CNVs in general.
期刊介绍：
Breast Cancer Research, an international, peer-reviewed online journal, publishes original research, reviews, editorials, and reports. It features open-access research articles of exceptional interest across all areas of biology and medicine relevant to breast cancer. This includes normal mammary gland biology, with a special emphasis on the genetic, biochemical, and cellular basis of breast cancer. In addition to basic research, the journal covers preclinical, translational, and clinical studies with a biological basis, including Phase I and Phase II trials.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
