Breast cancer research and treatment
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Breast Cancer Res. Treat. · Jun 2012
Randomized Controlled TrialA randomized trial of combination anastrozole plus gefitinib and of combination fulvestrant plus gefitinib in the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer.
EGFR signalling pathways appear involved in endocrine therapy resistance in breast cancer. This trial estimates the antitumor efficacy and toxicity of the EGFR tyrosine kinase inhibitor gefitinib in combination with anastrozole or fulvestrant in postmenopausal hormone receptor positive breast cancer. Subjects with estrogen receptor and/or PgR positive, metastatic breast cancer were randomized into this phase II study of gefitinib (initial dose was 500 mg orally daily, due to high rate of diarrhea, starting dose was reduced to 250 mg orally daily) with either anastrozole 1 mg daily or fulvestrant 250 mg every 4 weeks. ⋯ In general, the toxicity is greater than expected for single agent endocrine therapy alone. Anastrozole plus gefitinib and fulvestrant plus gefitinib have similar clinical benefit rates in the treatment of estrogen and/or PgR positive metastatic breast cancer, and the rates of response are not clearly superior to gefitinib or endocrine therapy alone. Further studies of EGFR inhibition plus endocrine therapy do not appear warranted, but if performed should include attempts to identify biomarkers predictive of antitumor activity.
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Breast Cancer Res. Treat. · May 2012
Randomized Controlled Trial Multicenter StudyHealth-related quality of life, psychological distress, and adverse events in postmenopausal women with breast cancer who receive tamoxifen, exemestane, or anastrozole as adjuvant endocrine therapy: National Surgical Adjuvant Study of Breast Cancer 04 (N-SAS BC 04).
Health-related quality of life (HRQOL), symptoms of depression, and adverse events (AEs) were compared between Japanese postmenopausal patients with hormone-sensitive breast cancer (BC) who received adjuvant tamoxifen, exemestane, or anastrozole in an open-labeled, randomized, multicenter trial designated as the National Surgical Adjuvant Study of Breast Cancer (N-SAS BC) 04 substudy of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. During the first year of treatment, HRQOL and symptoms of depression were analyzed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) and its Endocrine Symptom Subscale (ES), and the Center for Epidemiologic Studies Depression Scale (CES-D), respectively. In addition, predefined AEs were analyzed. ⋯ HRQOL was better in Japanese postmenopausal women treated with tamoxifen than those treated with exemestane or anastrozole. HRQOL and AEs were similar with exemestane and anastrozole. Given the results of the TEAM trial, upfront use of tamoxifen followed by an aromatase inhibitor (AI) may be an important option for adjuvant endocrine therapy in Japanese postmenopausal women.
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Breast Cancer Res. Treat. · Apr 2012
Randomized Controlled Trial Multicenter StudyEffect of baseline serum vitamin D levels on aromatase inhibitors induced musculoskeletal symptoms: results from the IBIS-II, chemoprevention study using anastrozole.
Severe deficiency of vitamin D in adults can cause musculoskeletal pain, stiffness, and joint discomfort. Musculoskeletal symptoms similar to those associated with vitamin D deficiency are frequently seen in breast cancer patients receiving adjuvant aromatase inhibitors (AIs). This is presumably due to oestrogen deficiency caused by AIs. ⋯ Absolute serum levels of vitamin D increased significantly at one year in the anastrozole group (2.88 ng/ml, [1.71, 4.06; P < 0.0001]) but not in the placebo group (0.75 ng/ml [-0.35, 1.85; P = 0.18]). Only a small and a nonsignificant effect of baseline vitamin D levels were seen on the risk of musculoskeletal symptoms. This does not appear to be a major determinant of risk for these symptoms.
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Breast Cancer Res. Treat. · Jan 2012
Randomized Controlled TrialA GINECO randomized phase II trial of two capecitabine and weekly paclitaxel schedules in metastatic breast cancer.
To determine whether capecitabine schedule adaptation improves the tolerability of capecitabine-paclitaxel combination therapy for metastatic breast cancer (MBC), patients with anthracycline-pretreated HER2-negative MBC were randomized to either arm A (21-day cycles: capecitabine 1,000 mg/m(2) twice daily, days 1-14; paclitaxel 60 mg/m(2), days 1, 8, and 15) or arm B (28-day cycles: capecitabine 1,000 mg/m(2) twice daily, days 1-5, 8-12, and 15-19; paclitaxel 80 mg/m(2), days 1, 8, and 15). The primary endpoint was the incidence of dose reductions or delays >1 week for grade 3/4 toxicity. Secondary endpoints were efficacy and safety. ⋯ Grade 3 diarrhea occurred in 12 and 0%, respectively, and grade 3 hand-foot syndrome in 12 versus 9%, respectively (grade 4 not applicable). There were no detectable differences in efficacy. Weekday capecitabine dosing with weekly paclitaxel may improve tolerability without a detrimental effect on efficacy, and merits further evaluation in patients suited to combination chemotherapy.
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Breast Cancer Res. Treat. · Aug 2011
Randomized Controlled Trial Multicenter Study Clinical TrialInteraction between goserelin and tamoxifen in a prospective randomised clinical trial of adjuvant endocrine therapy in premenopausal breast cancer.
Ovarian ablation improves survival in premenopausal early breast cancer, but the potential added value by luteinizing hormone-releasing hormone (LHRH) agonists to tamoxifen is still not clear. The purpose of our study is to examine the efficacy of the LHRH agonist goserelin for adjuvant therapy of premenopausal breast cancer, the role of interaction between goserelin and tamoxifen and the impact of estrogen receptor (ER) content. A total of 927 patients were included in the Stockholm part of the Zoladex in Premenopausal Patients (ZIPP) trial. ⋯ Women with strongly ER-positive tumours may benefit more from goserelin treatment. The combination of goserelin and tamoxifen is not superior to either modality alone. With the limitations of a subset trial, these data have to be interpreted cautiously.