Clinical outcomes based on multigene profiling in metastatic breast cancer patients

被引:23
作者
Basho, Reva K. [1 ]
Gagliato, Debora de Melo [2 ]
Ueno, Naoto T. [2 ]
Wathoo, Chetna [3 ]
Chen, Huiqin [4 ]
Shariati, Maryam [5 ]
Wei, Caimiao [4 ,6 ]
Alvarez, Ricardo H. [2 ,7 ]
Moulder, Stacy L. [2 ]
Sahin, Aysegul A. [8 ]
Roy-Chowdhuri, Sinchita [8 ]
Chavez-MacGregor, Mariana [2 ,9 ]
Litton, Jennifer K. [2 ]
Valero, Vincent [2 ]
Luthra, Raja [8 ]
Zeng, Jia [3 ]
Shaw, Kenna R. [3 ]
Mendelsohn, John [3 ,10 ]
Mills, Gordon B. [3 ,11 ]
Tripathy, Debu [2 ]
Meric-Bernstam, Funda [3 ,5 ,12 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA
[2] Univ Texas MD Anderson Canc Ctr, Breast Med Oncol, Houston, TX 77030 USA
[3] Univ Texas MD Anderson Canc Ctr, Sheikh Khalifa Bin Zayed Al Nahyan Inst Personali, Houston, TX 77030 USA
[4] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA
[5] Univ Texas MD Anderson Canc Ctr, Invest Canc Therapeut Phase Trials Program I, Houston, TX 77030 USA
[6] Pfizer Inc, New York, NY USA
[7] Canc Treatment Ctr Amer, Chicago, IL USA
[8] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
[9] Univ Texas MD Anderson Canc Ctr, Hlth Serv Res, Houston, TX 77030 USA
[10] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA
[11] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA
[12] Univ Texas MD Anderson Canc Ctr, Breast Surg Oncol, Houston, TX 77030 USA
关键词
metastatic breast cancer; genomics; TP53; PIK3CA; TRASTUZUMAB RESISTANCE; PIK3CA MUTATIONS; NEOADJUVANT TREATMENT; AMERICAN SOCIETY; TP53; MUTATION; GENE; PTEN; P53; ONCOLOGY/COLLEGE; RECOMMENDATIONS;
D O I
10.18632/oncotarget.12987
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND: Identifying the clinical impact of recurrent mutations can help define their role in cancer. Here, we identify frequent hotspot mutations in metastatic breast cancer (MBC) patients and associate them with clinical outcomes. PATIENTS AND METHODS: Hotspot mutation testing was conducted in 500 MBC patients using an 11 gene (N = 126) and/or 46 or 50 gene (N = 391) panel. Patients were stratified by hormone receptor (HR) and human epidermal growth factor 2 (HER2) status. Clinical outcomes were retrospectively collected. RESULTS: Hotspot mutations were most frequently detected in TP53 (30%), PIK3CA (27%) and AKT1 (4%). Triple-negative breast cancer (TNBC) patients had the highest incidence of TP53 (58%) and the lowest incidence of PIK3CA (9%) mutations. TP53 mutation was associated with shorter relapse-free survival (RFS) (median 22 vs 42months; P < 0.001) and overall survival (OS) from diagnosis of distant metastatic disease (median 26 vs 51months; P < 0.001). Conversely, PIK3CA mutation was associated with a trend towards better clinical outcomes including RFS (median 41 vs 30months; P = 0.074) and OS (52 vs 40months; P = 0.066). In HR-positive patients, TP53 mutation was again associated with shorter RFS (median 30 vs 46months; P = 0.017) and OS (median 30 vs 55months; P = 0.001). When multivariable analysis was performed for RFS and OS, TP53 but not PIK3CA mutation remained a significant predictor of outcomes in the overall cohort and in HR-positive patients. CONCLUSIONS: Clinical hotspot sequencing identifies potentially actionable mutations. In this cohort, TP53 mutation was associated with worse clinical outcomes, while PIK3CA mutation did not remain a significant predictor of outcomes after multivariable analysis.
引用
收藏
页码:76362 / 76373
页数:12
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