Hamdy A Azim, Hagar Elghazawy, Kyrillus S Shohdy, Shaimaa Lasheen, Mahmoud Elghazawy, Ramy Mohamed Ghazy, Dalia Abdelnasser, Loay Kassem
{"title":"BRCA突变对激素受体阳性/人表皮生长因子受体2阴性乳腺癌患者内分泌治疗±CDK4/6抑制剂治疗结果的影响：一项系统综述和荟萃分析","authors":"Hamdy A Azim, Hagar Elghazawy, Kyrillus S Shohdy, Shaimaa Lasheen, Mahmoud Elghazawy, Ramy Mohamed Ghazy, Dalia Abdelnasser, Loay Kassem","doi":"10.1200/PO-24-00841","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>The prognostic significance of <i>BRCA1/2</i> mutation and <i>RB1</i> alteration (Alt) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor-2-negative (HER2-) breast cancer (BC) treated with endocrine therapy (ET) ± cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) remains unresolved. This meta-analysis aimed to define their influence on therapy outcomes in the early and metastatic stages.</p><p><strong>Materials and methods: </strong>We systematically searched PubMed, Cochrane, and Google Scholar databases. Primary end points included disease-free (or progression-free) survival (DFS/PFS) and overall survival (OS) according to <i>BRCA1/2</i> mutation or <i>RB1 Alt</i> status. A separate analysis of individual-patient data for metastatic HR+/HER2- BC extracted from MSK-MET project was performed.</p><p><strong>Results: </strong>Twenty-two studies comprising 34,960 patients were eligible for meta-analysis. In the early setting, in eight studies (n = 7,857 patients with HR+ BC received ET), <i>BRCA1/2 mutant type</i> (<i>MT</i>) was associated with a marginally significant worse DFS (hazard ratio, 1.64 [95% CI, 1 to 2.69]; <i>P</i> = .05) and a significantly worse OS (hazard ratio, 1.52 [95% CI, 1.20 to 1.92]; <i>P</i> = .0006) versus <i>BRCA</i> wild-type (<i>WT</i>). In the metastatic setting, in 11 studies (n = 12,670 patients received ET+ CDK4/6i), <i>BRCA1/2</i> mutation was associated with a significantly worse PFS (hazard ratio, 1.87 [95% CI, 1.45 to 2.41]; <i>P</i> < .00001) and OS (hazard ratio, 1.38 [95% CI, 1.15 to 1.65]; <i>P</i> = .0005) versus <i>BRCA WT</i>. The individual-patient data confirmed the poorer prognosis of <i>BRCA2 MT</i> and <i>RB1 Alt</i>, but not <i>BRCA1 MT</i>, and a significant co-occurrence of <i>RB1</i> loss of heterozygosity (<i>LOH</i>) among <i>BRCA2 MT</i> carriers.</p><p><strong>Conclusion: </strong>The current analysis adds to the body of evidence supporting the inferior outcomes of ET± CDK4/6i in <i>BRCA MT</i> compared with <i>BRCA WT</i>. Given its significant coexistence with <i>RB1</i> LOH, <i>BRCA2 MT</i> BC seems uniquely resistant to ET± CDK4/6i, a point that is profoundly different from sporadic or even <i>BRCA1 MT</i> HR+/HER2- BC.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400841"},"PeriodicalIF":5.6000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impact of <i>BRCA</i> Mutation on Treatment Outcomes of Endocrine Therapy ± CDK4/6 Inhibitors in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor-2-Negative Breast Cancer: A Systematic Review and Meta-Analysis.\",\"authors\":\"Hamdy A Azim, Hagar Elghazawy, Kyrillus S Shohdy, Shaimaa Lasheen, Mahmoud Elghazawy, Ramy Mohamed Ghazy, Dalia Abdelnasser, Loay Kassem\",\"doi\":\"10.1200/PO-24-00841\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>The prognostic significance of <i>BRCA1/2</i> mutation and <i>RB1</i> alteration (Alt) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor-2-negative (HER2-) breast cancer (BC) treated with endocrine therapy (ET) ± cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) remains unresolved. This meta-analysis aimed to define their influence on therapy outcomes in the early and metastatic stages.</p><p><strong>Materials and methods: </strong>We systematically searched PubMed, Cochrane, and Google Scholar databases. Primary end points included disease-free (or progression-free) survival (DFS/PFS) and overall survival (OS) according to <i>BRCA1/2</i> mutation or <i>RB1 Alt</i> status. A separate analysis of individual-patient data for metastatic HR+/HER2- BC extracted from MSK-MET project was performed.</p><p><strong>Results: </strong>Twenty-two studies comprising 34,960 patients were eligible for meta-analysis. In the early setting, in eight studies (n = 7,857 patients with HR+ BC received ET), <i>BRCA1/2 mutant type</i> (<i>MT</i>) was associated with a marginally significant worse DFS (hazard ratio, 1.64 [95% CI, 1 to 2.69]; <i>P</i> = .05) and a significantly worse OS (hazard ratio, 1.52 [95% CI, 1.20 to 1.92]; <i>P</i> = .0006) versus <i>BRCA</i> wild-type (<i>WT</i>). In the metastatic setting, in 11 studies (n = 12,670 patients received ET+ CDK4/6i), <i>BRCA1/2</i> mutation was associated with a significantly worse PFS (hazard ratio, 1.87 [95% CI, 1.45 to 2.41]; <i>P</i> < .00001) and OS (hazard ratio, 1.38 [95% CI, 1.15 to 1.65]; <i>P</i> = .0005) versus <i>BRCA WT</i>. The individual-patient data confirmed the poorer prognosis of <i>BRCA2 MT</i> and <i>RB1 Alt</i>, but not <i>BRCA1 MT</i>, and a significant co-occurrence of <i>RB1</i> loss of heterozygosity (<i>LOH</i>) among <i>BRCA2 MT</i> carriers.</p><p><strong>Conclusion: </strong>The current analysis adds to the body of evidence supporting the inferior outcomes of ET± CDK4/6i in <i>BRCA MT</i> compared with <i>BRCA WT</i>. Given its significant coexistence with <i>RB1</i> LOH, <i>BRCA2 MT</i> BC seems uniquely resistant to ET± CDK4/6i, a point that is profoundly different from sporadic or even <i>BRCA1 MT</i> HR+/HER2- BC.</p>\",\"PeriodicalId\":14797,\"journal\":{\"name\":\"JCO precision oncology\",\"volume\":\"9 \",\"pages\":\"e2400841\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2025-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JCO precision oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/PO-24-00841\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/6 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-24-00841","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/6 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Impact of BRCA Mutation on Treatment Outcomes of Endocrine Therapy ± CDK4/6 Inhibitors in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor-2-Negative Breast Cancer: A Systematic Review and Meta-Analysis.
Purpose: The prognostic significance of BRCA1/2 mutation and RB1 alteration (Alt) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor-2-negative (HER2-) breast cancer (BC) treated with endocrine therapy (ET) ± cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) remains unresolved. This meta-analysis aimed to define their influence on therapy outcomes in the early and metastatic stages.
Materials and methods: We systematically searched PubMed, Cochrane, and Google Scholar databases. Primary end points included disease-free (or progression-free) survival (DFS/PFS) and overall survival (OS) according to BRCA1/2 mutation or RB1 Alt status. A separate analysis of individual-patient data for metastatic HR+/HER2- BC extracted from MSK-MET project was performed.
Results: Twenty-two studies comprising 34,960 patients were eligible for meta-analysis. In the early setting, in eight studies (n = 7,857 patients with HR+ BC received ET), BRCA1/2 mutant type (MT) was associated with a marginally significant worse DFS (hazard ratio, 1.64 [95% CI, 1 to 2.69]; P = .05) and a significantly worse OS (hazard ratio, 1.52 [95% CI, 1.20 to 1.92]; P = .0006) versus BRCA wild-type (WT). In the metastatic setting, in 11 studies (n = 12,670 patients received ET+ CDK4/6i), BRCA1/2 mutation was associated with a significantly worse PFS (hazard ratio, 1.87 [95% CI, 1.45 to 2.41]; P < .00001) and OS (hazard ratio, 1.38 [95% CI, 1.15 to 1.65]; P = .0005) versus BRCA WT. The individual-patient data confirmed the poorer prognosis of BRCA2 MT and RB1 Alt, but not BRCA1 MT, and a significant co-occurrence of RB1 loss of heterozygosity (LOH) among BRCA2 MT carriers.
Conclusion: The current analysis adds to the body of evidence supporting the inferior outcomes of ET± CDK4/6i in BRCA MT compared with BRCA WT. Given its significant coexistence with RB1 LOH, BRCA2 MT BC seems uniquely resistant to ET± CDK4/6i, a point that is profoundly different from sporadic or even BRCA1 MT HR+/HER2- BC.
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