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Advances in first-line treatment for patients with HER-2+ metastatic breast cancer.

ABSTRACT: The prognosis for breast cancer patients overexpressing human epidermal growth factor receptor (HER)-2 has changed with anti-HER-2-targeted therapy. Although anti-HER-2 therapy with trastuzumab and chemotherapy is the standard first-line treatment, the best therapeutic regimen has yet to be defined, and new strategies are evolving.A literature review of well-established and recently published trials, reviews, and ongoing clinical trials addressing first-line treatment for HER-2(+) metastatic breast cancer patients was performed.Taxanes are the agents most commonly used in combination with trastuzumab, but other chemotherapy drugs, such as anthracyclines, vinorelbine, and gemcitabine and triple-combination therapies including platinum compounds, capecitabine, and taxanes have been studied. The combination of aromatase inhibitors with anti-HER-2 therapies is a new therapeutic option for some patients who coexpress HER-2 and hormone receptors, although its activity observed in randomized clinical trials seems to be inferior to that of chemotherapy plus anti-HER-2 therapies. In addition, new anti-HER-2 therapies have shown activity in HER-2(+) tumors, both alone and in combination with trastuzumab.Trastuzumab plus chemotherapy is the current standard of care for the upfront treatment of HER-2(+) breast cancer patients, though other anti-HER-2-targeting agents may appear as new standards in the upcoming years.

SUBMITTER: De Mattos-Arruda L

PROVIDER: S-EPMC3360903 | biostudies-other | 2012

REPOSITORIES: biostudies-other

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Advances in first-line treatment for patients with HER-2+ metastatic breast cancer.

De Mattos-Arruda Leticia L Cortes Javier J

The oncologist 20120420 5

<h4>Background</h4>The prognosis for breast cancer patients overexpressing human epidermal growth factor receptor (HER)-2 has changed with anti-HER-2-targeted therapy. Although anti-HER-2 therapy with trastuzumab and chemotherapy is the standard first-line treatment, the best therapeutic regimen has yet to be defined, and new strategies are evolving.<h4>Methods</h4>A literature review of well-established and recently published trials, reviews, and ongoing clinical trials addressing first-line tr ...[more]

PMID: 22523199

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Project description:BACKGROUND:Intratumoral heterogeneity of 18F-fluorodeoxyglucose (18F-FDG) uptake in primary tumor has proven to be a surrogate marker for predicting treatment outcome in various tumors. However, the value of intraindividual heterogeneity in metastatic diseases remains unknown. The aim of this study was to evaluate pretreatment positron emission tomography/computed tomography (PET/CT) 18F-FDG-based heterogeneity for the prediction of first-line treatment outcome in metastatic triple-negative breast cancer (mTNBC). MATERIALS AND METHODS:mTNBC patients from three clinical trials (NCT00601159, NCT01287624, and NCT02341911) with whole-body 18F-FDG PET/CT scan before first-line gemcitabine/platinum were included. Heterogeneity index (HI) and the maximum of FDG uptake (MAX) across total metastatic lesions (-T) on baseline PET/CT scans were assessed. HI was measured by MAX divided by the minimum FDG uptake across metastatic lesions. Optimal cutoffs were determined by time-dependent receiver operator characteristics (ROC) analysis. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test. RESULTS:A total of 42 mTNBC patients were included in this study. The median PFS of patients with high HI-T (>1.9) and high MAX-T (>10.5) was significantly shorter than patients with low HI-T (<1.9; p = .049) and low MAX-T (<10.5; p = .001). In terms of OS, only high MAX-T was significant for poorer outcome (p = .013). ROC curve analysis confirmed the predictive value of MAX and HI in mTNBC patients. Area under the ROC curve for MAX-T and HI-T was 0.75 and 0.65, indicating a higher predictive accuracy than conventional clinical risk factors. CONCLUSION:HI and MAX measured among metastatic lesions on pretreatment 18F-FDG PET/CT scans could be potential predicators for first-line treatment outcome in patients with mTNBC. IMPLICATIONS FOR PRACTICE:Intratumoral heterogeneity of 18F-fluorodeoxyglucose (FDG) uptake in primary tumor has proven to be a robust surrogate predictive marker. A novel positron emission tomography/computed tomography (PET/CT) parameter-heterogeneity index (HI) to quantify the heterogeneous characteristics of metastatic disease is proposed. Triple-negative breast cancer (TNBC) is a highly heterogeneous disease and remains a clinical challenge. The predictive performance of HI, along with the maximum FDG uptake (MAX), measured on pretreatment PET/CT scans in patients with metastatic TNBC was evaluated. Results indicate that HI and MAX may serve as applicable imaging predicators for treatment outcome of metastatic TNBC in clinical practice.

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Advances in first-line treatment for patients with HER-2+ metastatic breast cancer.

Publications

Advances in first-line treatment for patients with HER-2+ metastatic breast cancer.

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