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Investigating the discernible and distinct effects of platinum-based chemotherapy regimens for metastatic triple-negative breast cancer on time to progression.

ABSTRACT: Platinum-based chemotherapy regimens are frequently used in patients with triple-negative breast cancer (TNBC). The aim of the current study was to assess whether or not platinum-based chemotherapy is associated with an increased time to progression when compared with non-platinum-based regimens in TNBC and non-TNBC. A retrospective analysis was conducted within a cohort of patients with metastatic breast cancer who received platinum-based chemotherapy at a single institution. Data were collected for up to three lines of treatment for metastatic disease. Time to progression was determined for platinum-based chemotherapy and non-platinum-based regimens for each line of treatment. Adjusted hazard ratios (HRs), together with 95% confidence intervals (CIs) were estimated comparing the time to progression associated with the use of platinum-based chemotherapy versus non-platinum-based regimens. A total of 159 patients were included in the analysis, with 58 diagnosed with TNBC. Among the patients with TNBC, compared with non-platinum-based chemotherapy, no correlation was identified between platinum-based chemotherapy and an improved time to progression [first line: HR, 0.97 (95% CI, 0.40-2.35); second line: HR, 0.91 (95% CI, 0.42-2.01); and third line: HR, 2.83 (95% CI, 0.73-11.03)]. By contrast, patients with non-TNBC appeared to improve with non-platinum-based chemotherapy [first line: HR, 2.57 (95% CI, 1.11-5.99); second line: HR, 1.91 (95% CI, 1.00-3.63); and third line: HR, 1.08 (95% CI, 0.53-2.18)]. Although the present study was limited by the sample size and its observational nature, the results indicated that platinum-based chemotherapy does not offer a discernible or distinct advantage compared with standard regimens in patients with TNBC, and is perhaps less efficacious in patients with non-TNBC.

SUBMITTER: Khalaf D

PROVIDER: S-EPMC3919882 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Investigating the discernible and distinct effects of platinum-based chemotherapy regimens for metastatic triple-negative breast cancer on time to progression.

Khalaf Daniel D Hilton John F JF Clemons Mark M Azoulay Laurent L Yin Hui H Vandermeer Lisa L Dent Susan S Hopkins Sean S Bouganim Nathaniel N

Oncology letters 20140107 3

Platinum-based chemotherapy regimens are frequently used in patients with triple-negative breast cancer (TNBC). The aim of the current study was to assess whether or not platinum-based chemotherapy is associated with an increased time to progression when compared with non-platinum-based regimens in TNBC and non-TNBC. A retrospective analysis was conducted within a cohort of patients with metastatic breast cancer who received platinum-based chemotherapy at a single institution. Data were collecte ...[more]

PMID: 24527094

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Project description:PurposeTo determine whether specific somatic copy-number alterations detectable in circulating tumor DNA (ctDNA) from patients with metastatic triple-negative breast cancer (mTNBC) are associated with sensitivity to platinum chemotherapy.Materials and methodsIn this secondary analysis of a large cohort of patients with mTNBC whose ctDNA underwent ultralow-pass whole-genome sequencing, tumor fraction and somatic copy-number alterations were derived with the ichorCNA algorithm. Seventy-two patients were identified who had received a platinum-based chemotherapy regimen in the metastatic setting. Gene-level copy-number analyses were performed with GISTIC2.0. Cytobands were associated with progression-free survival (PFS) to platinum chemotherapy using Cox proportional hazards models. The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium data sets were interrogated for frequency of significant cytobands in primary triple-negative breast cancer (pTNBC) tumors.ResultsAmong 71 evaluable patients, 17q21 and 17q22 amplifications were most strongly associated with improved PFS with platinum chemotherapy. There were no significant differences in clinicopathologic features or (neo)adjuvant chemotherapy among patients with 17q22 amplification. Patients with 17q22 amplification (n = 17) had longer median PFS with platinum (7.0 v 3.8 months; log-rank P = .015) than patients without 17q22 amplification (n = 54), an effect that remained significant in multivariable analyses (PFS hazard ratio 0.37; 95% CI, 0.16 to 0.84; P = .02). Among 39 patients who received the nonplatinum chemotherapy agent capecitabine, there was no association between 17q22 amplification and capecitabine PFS (log-rank P = .69). In The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium, 17q22 amplification occurred in more than 20% of both pTNBC and mTNBC tumors, whereas 17q21 was more frequently amplified in mTNBC relative to pTNBC (16% v 8.1%, P = .015).ConclusionThe 17q22 amplicon, detected by ctDNA, is associated with improved PFS with platinum chemotherapy in patients with mTNBC and warrants further investigation.

Project description:BACKGROUND:Chemotherapy resistance is a great obstacle in effective treatment for metastatic triple negative breast cancer (TNBC). The ability to predict chemotherapy response would allow chemotherapy administration to be directed toward only those patients who would benefit, thus maximizing treatment efficiency. Differentially expressed plasma proteins may serve as putative biomarkers for predicting chemotherapy outcomes. PATIENTS AND METHODS:In this study, 26 plasma samples (10 samples with partial response (S) and 16 samples with progression disease (R)) from patients with metastatic TNBC were measured by Tandem Mass Tag (TMT)-based proteomics analysis to identify differentially expressed proteins between the S and R group. Potential proteinswere validated with enzyme-linked immunosorbent assay (ELISA) in another 67 plasma samples. RESULTS:A total of 320 plasma proteins were identified, and statistical analysis showed that 108 proteins were significantly dysregulated between R and S groups in the screening stage. Bioinformatics revealed relevant pathways and regulatory networks of the differentially expressed proteins. Three differentially expressed proteins were validated by ELISA with 67 samples from TNBC patients. The R group had significantly higher plasma CAMK2A level than the S group (P=0.0074). The ROC curve analysis showed an AUC of 0.708, with sensitivity 48.4% and specificity 86.1%. In multivariate logistic regression analysis, the level of plasma CAMK2A was also significant for chemotherapeutic response (P=0.009, OR=0.152). Furthermore, the patients with higher CAMK2A level had shorter OS than those with lower CAMK2A level, which amounted to 13.9 and 28.9 months, respectively (P=0.034). In the multivariate Cox regression analysis, CAMK2A level still had significant effect on OS (P=0.031, HR=1.865). CONCLUSION:TMT-based proteomic analysis was able to identify potential biomarkers in plasma that predicted chemotherapy resistance in the metastatic TNBC. The plasma of CAMK2A level may serve as apotential predictive and prognostic biomarker for chemotherapy in metastatic TNBC.

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Investigating the discernible and distinct effects of platinum-based chemotherapy regimens for metastatic triple-negative breast cancer on time to progression.

Publications

Investigating the discernible and distinct effects of platinum-based chemotherapy regimens for metastatic triple-negative breast cancer on time to progression.

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