Dataset Information

Clinical outcomes based on multigene profiling in metastatic breast cancer patients.

ABSTRACT:

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.

SUBMITTER: Basho RK

PROVIDER: S-EPMC5363515 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Publications

Clinical outcomes based on multigene profiling in metastatic breast cancer patients.

Basho Reva K RK de Melo Gagliato Debora D Ueno Naoto T NT Wathoo Chetna C Chen Huiqin H Shariati Maryam M Wei Caimiao C Alvarez Ricardo H RH Moulder Stacy L SL Sahin Aysegul A AA Roy-Chowdhuri Sinchita S Chavez-MacGregor Mariana M Litton Jennifer K JK Valero Vincent V Luthra Raja R Zeng Jia J Shaw Kenna R KR Mendelsohn John J Mills Gordon B GB Tripathy Debu D Meric-Bernstam Funda F

Oncotarget 20161101 47

<h4>Background</h4>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.<h4>Patients and methods</h4>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. Clin ...[more]

PMID: 27806348

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Project description:BackgroundImmuno-oncology (IO) agents have demonstrated efficacy across many tumor types and have led to change in standard of care. In breast cancer, atezolizumab and pembrolizumab were recently FDA-approved in combination with chemotherapy specifically for patients with PD-L1-positive metastatic triple-negative breast cancer (TNBC). However, the single agent PD-1/PD-L1 inhibitors demonstrate only modest single agent efficacy in breast cancer. The purpose of this study was to investigate the efficacy of novel IO agents in patients with metastatic breast cancer (MBC), beyond TNBC, treated in phase I clinical trials at the University of Colorado.MethodsWe performed a retrospective analysis using a database of patients with MBC who received treatment with IO agents in phase I/Ib clinical trials at the University of Colorado Hospital from January 1, 2012 to July 1, 2018. Patient demographics, treatments and clinical outcomes were obtained.ResultsWe identified 43 patients treated with an IO agent either as a single agent or in combination. The average age was 53 years; 55.8% had hormone receptor-positive/HER2-negative breast cancer, 39.5% TNBC and 4.7% HER2-positive. Patients received an average of 2 prior lines of chemotherapy (range 0-7) in the metastatic setting. Most patients (72.1%) received IO alone and 27.9% received IO plus chemotherapy. Median progression-free survival (PFS) was 2.3 months and median overall survival (OS) was 12.1 months. Patients remaining on study ≥ 6 months (20.9%) were more likely to be treated with chemotherapy plus IO compared to patients with a PFS < 6 months (77.8% v. 14.7%). No differences in number of metastatic sites, prior lines of chemotherapy, breast cancer subtype, absolute lymphocyte count, or LDH were identified between patients with a PFS ≥ 6 months vs. < 6 months.ConclusionsOur phase I experience demonstrates benefit from IO therapy that was not limited to patients with TNBC and confirms improved efficacy from IO agents in combination with chemotherapy. A subset of patients with MBC treated in phase I clinical trials with an IO agent derived prolonged clinical benefit. Predictors of response to immunotherapy in breast cancer remain uncharacterized and further research is needed to identify these factors.

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Dataset Information

Clinical outcomes based on multigene profiling in metastatic breast cancer patients.

Background

Patients and methods

Results

Conclusions

Publications

Clinical outcomes based on multigene profiling in metastatic breast cancer patients.

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