Haas JS, Liang SY, Hassett MJ, Shiboski S, Elkin EB, Phillips KAGene expression profile testing for breast cancer and the use of chemotherapy, serious adverse effects, and costs of care. Breast Cancer Res Treat 130: 619-626
Division of General Medicine and Primary Care, Brigham and Women's Hospital, 1620 Tremont Street, Boston, MA 02120, USA. Breast Cancer Research and Treatment
(Impact Factor: 3.94).
06/2011; 130(2):619-26. DOI: 10.1007/s10549-011-1628-6
As gene expression profile (GEP) testing for breast cancer may provide additional prognostic information to guide the use of adjuvant chemotherapy, we examined the association between GEP testing and use of chemotherapy, serious chemotherapy-related adverse effects, and total charges during the 12 months following diagnosis. Medical record review was conducted for women age 30-64 years, with incident, non-metastatic, invasive breast cancer diagnosed 2006-2008 in a large, national health plan. Of 534 patients, 25.8% received GEP testing, 68.2% received chemotherapy, and 10.5% experienced a serious chemotherapy-related adverse effect. GEP testing was most commonly used in women at moderate clinical risk of recurrence (52.0 vs. 25.0% of low-risk women and 5.5% of high-risk). Controlling for the propensity to receive GEP testing, women who had GEP were less likely to receive chemotherapy (propensity adjusted odds ratio, 95% confidence interval 0.62, 0.39-0.99). Use of GEP was associated with more chemotherapy use among women at low risk based on clinical characteristics (OR = 42.19; CI 2.50-711.82), but less use among women with a high risk based on clinical characteristics (OR = 0.12; CI 0.03-0.47). Use of GEP was not associated with chemotherapy for the moderate risk group. There was no significant relationship between GEP use and either serious chemotherapy-associated adverse effects or total charges. While GEP testing was associated with an overall decrease in adjuvant chemotherapy, we did not find differences in serious chemotherapy-associated adverse events or charges during the 12 months following diagnosis.
Available from: Elisabeth Edström Elder
- "Gene expression profiling is emerging as a tool for classifying breast cancers, guiding therapy, and predicting treatment responses (Cheang et al, 2008; Haas et al, 2011). However, genome and transcriptome analyses alone provide only a partial picture, as alternative splicing of mRNA, combined with more than 100 unique post-translational protein modifications, mean that each gene may give rise to multiple protein species (Banks et al, 2000). "
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Tissue protein expression profiling has the potential to detect new biomarkers to improve breast cancer (BC) diagnosis, staging, and prognostication. This study aimed to identify tissue proteins that differentiate breast cancer tissue from healthy breast tissue using protein chip mass spectrometry and to examine associations with conventional pathological features.
To develop a training model, 82 BC and 82 adjacent unaffected tissue (AT) samples were analysed on cation-exchange protein chips by time-of-flight mass spectrometry. For validation, 89 independent BC and AT sample pairs were analysed.
From the protein peaks that were differentially expressed between BC and AT by univariate analysis, binary logistic regression yielded two peaks that together classified BC and AT with a ROC area under the curve of 0.92. Two proteins, ubiquitin and S100P (in a novel truncated form), were identified by liquid chromatography/tandem mass spectrometry and validated by immunoblotting and reactive-surface protein chip immunocapture. The combined marker panel was positively associated with high histologic grade, larger tumour size, lymphovascular invasion, ER and PR positivity, and HER2 overexpression, suggesting that it may be associated with a HER2-enriched molecular subtype of breast cancer.
This independently validated protein panel may be valuable in the classification and prognostication of breast cancer patients.
British Journal of Cancer 01/2013; 108(2). DOI:10.1038/bjc.2012.552 · 4.84 Impact Factor
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ABSTRACT: Aims: Trastuzumab, one of the best known examples of personalized medicine, requires regular cardiac monitoring because it can cause heart failure. We aimed to assess the utilization of cardiac monitoring in women with nonmetastatic breast cancer receiving trastuzumab-based chemotherapy in routine clinical practice. Patients & methods: The medical records of women continuously enrolled in a large national health insurance plan who were diagnosed with nonmetastatic breast cancer and treated with trastuzumab from 2006 to 2008 were reviewed (n = 109). The primary outcome variables were the use and type of cardiac monitoring testing before and during trastuzumab therapy. An exploratory multivariable logistic regression analysis was performed to identify predictors for receiving cardiac monitoring both at baseline and during trastuzumab treatment. Results: Monitoring both before and during therapy was less common (62%), although 74% had cardiac monitoring before therapy and 80% had at least one test during therapy. Radionuclide ventriculogram was utilized more often than echocardiography (48 vs 42%). Only the use of anthracycline (odds ratio: 2.39; 95% CI: 1.01-5.71) was significantly associated with use of a cardiac monitoring both at baseline and during trastuzumab treatment. Conclusion: The use of cardiac monitoring testing was variable and opportunities to improve quality and reduce cost are evident. These results have clinical implications for other personalized medicine interventions requiring regular laboratory monitoring.
Personalized Medicine 09/2013; 10(7):703-708. DOI:10.2217/pme.13.68 · 1.34 Impact Factor
Available from: spandidos-publications.com
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ABSTRACT: Oncolytic adenoviruses are a novel class of anticancer treatment, based upon their ability to replicate selectively within malignant cells resulting in cell lysis. The replication‑selective adenovirus, ZD55‑IL‑24, was constructed by harboring an E1B‑55 kDa deletion and arming with interleukin-24 (IL-24). The microtubule‑stabilizing drug paclitaxel (PTX) exhibits activity in relapsed cancer. In the present study, the synergistic antitumor effects of the combination of PTX and ZD55‑IL‑24 on breast cancer cells was investigated. The results demonstrated that there were different roles for PTX in the expression of transgenic mRNA and protein. ZD55‑IL‑24 combined with PTX induced marked growth inhibition of MDA‑MB‑231 and Bcap‑37 cells. PTX increased viral uptake and appeared not to alter the replication of ZD55‑IL‑24 in breast cancer cells. Annexin V‑fluorescein isothiocyanate/propidium iodide staining and the Hoechst 33258 assay indicated that ZD55‑IL‑24 induced an increase in the number of apoptotic cells when administered in combination with PTX. It was demonstrated that ZD55‑IL‑24 conjugated with PTX was highly concomitant, and increased proapoptotic proteins levels, activated caspase‑3, -7 and -9 and downregulated anti‑apoptotic proteins. These results suggested that ZD55‑IL‑24 in combination with PTX exhibited a markedly increased cytotoxic and apoptosis‑inducing effect in breast cancer cells. Thus, this chemo‑gene‑viro therapeutic strategy was demonstrated to be superior to conventional chemotherapy or gene‑viro therapy alone.
Molecular Medicine Reports 09/2013; 8(5). DOI:10.3892/mmr.2013.1680 · 1.55 Impact Factor
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