Breast cancer research and treatment
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Breast Cancer Res. Treat. · Nov 2013
Randomized Controlled TrialPhase II randomized trial of weekly and every-3-week ixabepilone in metastatic breast cancer patients.
This multicenter, open-label, randomized phase II trial compared the efficacy and tolerability of weekly ixabepilone versus the standard 3 weekly dosing regimen. Patients with human epidermal growth factor receptor 2-negative, metastatic breast cancer (MBC) were randomly assigned to receive either ixabepilone 16 mg/m(2) as a 1-h intravenous (IV) infusion weekly on days 1, 8, and 15 of a 28-day cycle (1 week off therapy; n = 85), or 40 mg/m(2) as a 3-h IV infusion on day 1 of a 21-day cycle (n = 91), until disease progression or unacceptable toxicity. Randomization was stratified by (i) measurable versus nonmeasurable (evaluable) disease, (ii) ≤two versus >two prior chemotherapy regimens for MBC, and (iii) hormone receptor (HR)-positive versus HR-negative breast cancer. ⋯ Every-3-week dosing significantly prolonged median PFS versus weekly dosing (5.3 vs. 2.9 months; log-rank P = 0.05). The every-3-week regimen was associated with higher rates of grade 3/4 toxicities, particularly neutropenia (38.2 vs. 6.1 %) and a higher rate of patient withdrawal due to adverse events. These results suggest that every-3-week ixabepilone is more effective than weekly treatment in MBC, albeit with more toxicity.
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Breast Cancer Res. Treat. · Nov 2013
Randomized Controlled Trial Multicenter StudyTreatment of older patients with HER2-positive metastatic breast cancer with pertuzumab, trastuzumab, and docetaxel: subgroup analyses from a randomized, double-blind, placebo-controlled phase III trial (CLEOPATRA).
Although the incidence of cancer increases with age, older patients are under-represented in cancer treatment trials, resulting in limited data availability in this patient population. Here we present results from pre-defined subgroup analyses conducted by age group (<65 vs ≥ 65 years) from a randomized, double-blind, placebo-controlled phase III trial in patients with HER2-positive metastatic breast cancer. Patients who had not received previous chemotherapy or biological therapy for HER2-positive locally recurrent, unresectable or metastatic breast cancer were randomly assigned to treatment with placebo, trastuzumab, and docetaxel or with pertuzumab, trastuzumab, and docetaxel. ⋯ Diarrhoea, fatigue, asthenia, decreased appetite, vomiting, and dysgeusia were reported more frequently in patients 65 years of age or older compared with younger patients. Neutropenia and febrile neutropenia were reported less frequently in the older age group. The efficacy and safety data reported in CLEOPATRA suggest that the combined use of pertuzumab, trastuzumab, and docetaxel should not be limited by patient age.
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Breast Cancer Res. Treat. · Nov 2013
Randomized Controlled Trial Multicenter StudyPreliminary results of centralized HER2 testing in ductal carcinoma in situ (DCIS): NSABP B-43.
NSABP B-43 is the first prospective, randomized phase III multi-institution clinical trial targeting high-risk, HER2-positive DCIS. It compares whole breast irradiation alone with WBI given concurrently with trastuzumab in women with HER2-positive DCIS treated by lumpectomy. The primary aim is to determine if trastuzumab plus radiation will reduce in-breast tumor recurrence. ⋯ In NSABP B-43 the HER2-positive rate for pure DCIS among patients undergoing breast-preserving surgery is 34.9 %, lower than the previously reported rate. No trastuzumab-related safety signals have been observed. Interest in this trial has been robust.
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Breast Cancer Res. Treat. · Nov 2013
Trastuzumab-related cardiac events in the treatment of early breast cancer.
Trastuzumab is considered a cornerstone in the treatment of human epidermal growth factor receptor-2 (HER2)-positive breast cancer. Cardiac toxicity is an important side effect of treatment and can limit the use of this drug known to act synergistically with cardiotoxicity from anthracyclines. A retrospective study was performed on breast cancer patients with early breast cancer, and HER2 overexpression treated with adjuvant/neoadjuvant chemotherapy and trastuzumab between 2005 and 2010. ⋯ The incidence of cardiac toxicity with trastuzumab adjuvant treatment in our study is similar to other reports. Only radiotherapy to the left chest wall increased the risk for CE. Further prospective studies are needed, including echocardiographic measurement and biochemical data (troponin I), for early recognition and monitoring of high-risk patients.
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Breast Cancer Res. Treat. · Nov 2013
Preemptive tumor profiling for biomarker-stratified early clinical drug development in metastatic breast cancer patients.
Biomarker-stratified cancer pharmacotherapy was pioneered in the care of breast cancer patients. The utility of agents modulating hormone receptors, synthesis of steroid hormones, or HER2-targeting agents has been greatly enhanced by the detection of predictive biomarkers in diagnostic tumor samples. Based on deeper understanding of breast cancer biology multiple drug candidates have been developed to modulate additional molecular targets which may associate with specific biomarker profiles. ⋯ So far 16 “profiled” patients (12 %) have been enrolled in biomarker-stratified early clinical trials. Preemptive profiling of investigational biomarkers can be integrated into the diagnostic algorithm of a large Comprehensive Cancer Center. Extensive administrative efforts are required to successfully enroll “profiled” patients with metastatic breast cancer in early clinical trials stratified by exploratory biomarkers.