Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to compare changes in bone mineral density (BMD) in premenopausal patients with node-positive early breast cancer treated with goserelin (Zoladex) or cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Patients ( n=1640) were randomized to goserelin (3.6 mg every 28 days for 2 years) or CMF (sixx28-day cycles) treatment. In a protocoled sub-study involving 96 patients from eight centers (goserelin: n=53; CMF: n=43), lumbar spine (L2-L4) and femoral neck BMD were assessed by dual X-ray absorptiometry at baseline and then annually for 3 years. At the end of the 2-year goserelin-treatment period, mean BMD losses for goserelin-treated and CMF-treated patients were -10.5% and -6.5% ( P=0.0005) for lumbar spine and -6.4% and -4.5% ( P=0.04) for femoral neck, respectively. At 3 years, partial recovery of BMD was observed in goserelin recipients. In contrast, mean BMD losses for the CMF group indicated persistent BMD loss. No significant differences in BMD were observed between groups at the 3-year assessment of the spine or femoral neck. In the CMF group, based on amenorrhea status at 48 weeks, BMD losses at the lumbar spine were greater for amenorrheic than non-amenorrheic patients. Ovarian suppression resulting in amenorrhea was closely related to BMD loss in both treatment groups. Overall, patients who received CMF did not show recovery of BMD throughout follow-up, whereas partial recovery was observed 1 year after cessation of goserelin therapy, associated with the return of ovarian function in the majority of patients.
 ...
PMID:Bone mineral density in premenopausal women treated for node-positive early breast cancer with 2 years of goserelin or 6 months of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). 1453 Sep 12

The use of adjuvant endocrine therapy in the treatment of hormone receptor-positive, early breast cancer has become important in both pre- and postmenopausal women. Tamoxifen has been the principal adjuvant hormonal therapy in pre- and postmenopausal women with hormone receptor-positive breast cancer for nearly 20 years. Recent data in premenopausal women suggest benefit from ovarian ablation with or without tamoxifen. Early results from the 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial have demonstrated that the third-generation, selective aromatase inhibitor (AI) anastrozole ('Arimidex') is a suitable alternative adjuvant therapy for postmenopausal women with hormone receptor-positive disease. After recurrence or relapse on adjuvant endocrine therapy, responses to the sequential use of additional endocrine agents are common. The increase in the number of options now available for adjuvant therapy will have important implications for the selection of the optimal sequence of endocrine agents in the treatment of recurrent breast cancer. Menopausal status is an important factor in determining the endocrine therapy that a patient receives. For premenopausal women, tamoxifen and/or a luteinizing hormone-releasing hormone agonist such as goserelin ('Zoladex') are both options for adjuvant endocrine treatment. After progression on adjuvant and first-line tamoxifen, ovarian ablation is an appropriate second-line therapy. For premenopausal women who have undergone ovarian ablation, the use of third-line therapy with an AI becomes possible. For postmenopausal women, a wide choice of endocrine treatment options is available and an optimal sequence has yet to be determined. Options for first-line therapy of metastatic disease include an AI for women who have received adjuvant tamoxifen or tamoxifen for patients who have received adjuvant anastrozole. In addition, data suggest that fulvestrant ('Faslodex'), a novel estrogen receptor (ER) antagonist that downregulates the ER protein and has no known agonist effects, is a promising therapeutic option that has shown efficacy in the treatment of postmenopausal women with advanced breast cancer. Other agents that may be used in the sequence include the steroidal AI exemestane and the progestin megestrol acetate. The widening range of adjuvant endocrine options therefore represents an opportunity to prolong patient benefits in the treatment of hormone receptor-positive breast cancer, and will require the further refinement of the optimal sequence of endocrine agents for the treatment of recurrent breast cancer.
Breast Cancer Res Treat 2003
PMID:Sequential hormonal therapy for metastatic breast cancer after adjuvant tamoxifen or anastrozole. 1453 31

During the recently held 8th International Conference on Primary Therapy of Early Breast Cancer, (March 12-15, 2003 St. Gallen/Switzerland) established recommendations for adjuvant endocrine treatment were confirmed, while new options were introduced. Ovarian ablation, limited for 2 years (e. g. Goserelin, combined with 5 years of Tamoxifen), was suggested as an effective treatment option in premenopausal patients with a hormonsensitive breast cancer. The efficacy of this endocrine regimen is equivalent to CMF-chemotherapy in these patients. In "very" young patients with hormonsensitive tumors, chemotherapy alone is not sufficient. These patients will particularly benefit from endocrine treatment. The reversibility of endocrine treatment is its main advantage, avoiding long lasting symptoms of hormone deficiency. In postmenopausal hormonsensitive patients the aromatase inhibitor Anastrozol (Arimidex trade mark ) has been approved as an alternative for patients with contraindications against Tamoxifen (e. g. increased risk of thromboembolism, varicosis, smokers, endometrium changes). The initiation of endocrine should be postponed until the completion of chemotherapy, because combined application reduces the efficacy of adjuvant treatment. "Older" patients will get only limited advantage of chemoendocrine treatment compared to endocrine treatment alone. Preliminary treatment recommendations comprise a wide range of possible treatment options.
 ...
PMID:[Adjuvant endocrine treatment of breast cancer beyond St. Gallen 2003]. 1456 10

A total of 16 premenopausal women with metastatic breast cancer (N=13) or locally advanced primary breast cancer (N=3) were treated with a combination of a gonadotropin-releasing hormone agonist goserelin, and a selective aromatase inhibitor anastrozole. All had previously been treated with goserelin and tamoxifen. In all, 12 patients (75%) achieved objective response or durable stable disease at 6 months, with a median duration of remission of 17+ months (range 6-47 months). Four patients still have clinical benefit. Introduction of goserelin and tamoxifen resulted in an 89% reduction in mean oestradiol levels (pretreatment vs 6 months=224 vs 24 pmol l(-1)) (P<0.0001). Substitution of tamoxifen by anastrozole on progression resulted in a further 76% fall (to 6 pmol l(-1) at 3 months) (P<0.0001). Treatment with goserelin and tamoxifen led to a 90% fall in the mean follicle-stimulating hormone (P<0.001). This was reversed once therapy was changed to goserelin and anastrozole. A similar initial reduction was seen in the mean luteinising hormone levels, but substitution of tamoxifen by anastrozole on progression resulted in no significant change. Goserelin and tamoxifen did not lead to any significant change in testosterone and androstenedione levels. The combined use of goserelin and anastrozole as second-line endocrine therapy produces a significant clinical response of worthwhile duration, with demonstrable endocrine changes, in premenopausal women with advanced breast cancer, and offers them another therapeutic option. Further studies involving more patients and longer follow-up are indicated.
 ...
PMID:Clinical and endocrine data for goserelin plus anastrozole as second-line endocrine therapy for premenopausal advanced breast cancer. 1558 87

Postoperative adjuvant drugs are usually given long-term for breast cancer to obtain various effects and their effects on serum lipid level changes were studied. Between June 1990 and May 2003, changes in serum levels of five serum lipids, cholesterol (CHO), triglyceride (TG), phospholipid (PL), free fatty acid (FFA), and high-density lipoprotein-cholesterol (HDL-C), were quantitated for 453 surgically-treated patients with breast cancer. Postoperative adjuvant settings were: 1. no drug; 2. Goserelin (G) of subcutaneous gradual release form; 3. tamoxifen; 4. oral fluoropyrimidines, i. e. tegafur, carmofur and doxyfluridine; and 5. oral alkylating agents, i. e. carboquone or cyclophosphamide. Preoperative levels of all five lipids correlated with age until 70, and postoperative levels of all five increased. The CHO level increased in patients treated with G, fluoropyrimidines and oral alkylating agents, decreased in patients treated with tamoxifen, and was stable in patients without adjuvant treatment. While the increase in the CHO level in G or decrease in tamoxifen was restored nearly to the preoperative level, the changes in patients with fluoropyrimidines or alkylating agents continued after five-year administration. Multiple regression analysis revealed significant effects of preoperative levels of all lipids, including T for CHO, G and oral fluoropyrimidines for TG, G for FFA, and oral fluoropyrimidines for PL. While postoperative adjuvant treatment for breast cancer affects changes in serum lipid levels as a function of preoperative level and age, it seems to be due to direct or indirect endocrine milieu.
 ...
PMID:[Postoperative changes in serum lipid levels of breast cancer and adjuvant chemotherapy]. 1550 43

The luteinising hormone-releasing hormone analogue goserelin ('Zoladex') suppresses ovarian oestrogen production in pre- and perimenopausal women. Goserelin is a biodegradable, sustained-release 3.6 mg depot that is administered by subcutaneous injection every 28 days. Clinical trials in premenopausal women with hormone-sensitive early breast cancer have demonstrated that goserelin alone, or in combination with tamoxifen, is at least as effective as cyclophosphamide, methotrexate, 5-fluorouracil (CMF) chemotherapy. Goserelin plus tamoxifen after cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) chemotherapy resulted in improved disease-free survival compared with CAF alone. These trials have also shown that goserelin is well tolerated and is associated with less acute toxicity than cytotoxic chemotherapy. Early improvements in quality of life over the first 3-6 months of goserelin treatment support the use of this agent as an alternative to chemotherapy in this patient population. Patients should be provided with information on the benefits and risks associated with available treatment options so that they can be involved in the decision-making process.
 ...
PMID:Goserelin ('Zoladex')--offering patients more choice in early breast cancer. 1559 Mar 21

Gonadotropin-releasing hormone analogs are, alongside tamoxifen, one of the most commonly used drugs in the treatment of pre-/perimenopausal endocrine-responsive breast cancer. Goserelin, as a principal agent of this class of drugs, is mainly investigated in clinical trials. The indirect comparison of goserelin with tamoxifen as a single drug in the adjuvant setting showed similar efficacy. Furthermore, goserelin is as effective as cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy, and total endocrine blockade as a combination of gonadotropin-releasing hormone analog and tamoxifen showed a comparable benefit with anthracycline-containing adjuvant chemotherapy. Goserelin administered after cessation of chemotherapy leads to a further improvement and may be equieffective as tamoxifen or a combination of both. Data concerning taxane-based and dose-dense chemotherapy as well as combination of gonadotropin-releasing hormone analogs with third-generation aromatase inhibitors are still lacking (ongoing suppression of ovarian function, tamoxifen and exemestane, and premenopausal endocrine-responsive chemotherapy trials). Moreover, duration of therapy with gonadotropin-releasing hormone analogs (2-3 years or longer) is still a matter of debate. Palliative endocrine treatment is standard in the first-line therapy of patients without life-threatening disease and endocrine-responsive breast cancer. Treatment decisions depend upon adjuvant endocrine pretreatment. Clinical data regarding ovarian protection by synchronous use of gonadotropin-releasing hormone in young breast cancer patients receiving chemotherapy are incoherent.
 ...
PMID:Use of goserelin in the treatment of breast cancer. 1611 61

Goserelin (Zoladex), a gonadotropin-releasing hormone analogue, reduces plasma/serum estrogen levels in pre- or perimenopausal women (to postmenopausal levels), and is indicated in hormone receptor-positive early breast cancer in this population group. Adjuvant goserelin monotherapy has similar efficacy to adjuvant chemotherapy in pre- or perimenopausal women with early, hormone receptor-positive breast cancer. Furthermore, the addition of goserelin to adjuvant chemotherapy appeared to offer an advantage over chemotherapy alone in younger patients. Fewer patients remained amenorrheic after goserelin therapy than after chemotherapy. Complete endocrine blockade provided by the addition of tamoxifen to therapy including goserelin appears to improve outcomes. Thus, goserelin offers a valuable addition to the currently available options for treating pre- or perimenopausal women with hormone therapy-responsive early breast cancer, particularly for women wishing to regain ovarian function after treatment.
 ...
PMID:Goserelin: a review of its use in the treatment of early breast cancer in premenopausal and perimenopausal women. 1639 82

The Zoladex In Pre-menopausal Patients (ZIPP) study was designed to determine whether addition of goserelin ('Zoladex') and/or tamoxifen to adjuvant therapy (radiotherapy and/or chemotherapy), provided benefit to pre- or peri-menopausal women with operable, early breast cancer. A combined analysis of four randomised trials using a core protocol was performed. Patients (n = 2710) were randomised into a 2 x 2 factorial trial based on goserelin and tamoxifen (n = 1800) or randomised to receive goserelin or not (n = 910; some received elective tamoxifen) for 2 years. The analysis presented here compares women who did (n = 1354) or did not (n = 1356) receive goserelin. After a median follow-up of 5.5 years, goserelin provided a significant benefit for event-free survival (hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.69, 0.92; P = 0.002) and overall survival (HR 0.81; 95% CI 0.67, 0.99; P = 0.038). Goserelin was well tolerated. These data show that the addition of goserelin to standard adjuvant therapy is more effective than standard therapy alone in pre-menopausal women with early breast cancer.
 ...
PMID:Adjuvant goserelin in pre-menopausal patients with early breast cancer: Results from the ZIPP study. 1654 60

Adjuvant ovarian function suppression is acknowledged today as effective therapy for premenopausal patients with early breast cancer. Various modalities have been applied to achieve this treatment option: First, early investigations comparing ovarian ablation with chemotherapy identified similar outcomes in terms of patients' rates of disease-free survival (DFS). Second, prospective randomized trials have more recently focused on luteinizing hormone-releasing hormone analogues (LHRHa) that induce medical ovarian suppression and avoid the morbidity and irreversibility associated with surgical ovariectomy or irradiation. These trials analyzed the value of treatment with goserelin or other LHRHa, with or without tamoxifen, as against chemotherapy. Goserelin was subsequently established as a valid alternative, and our own results demonstrated that goserelin + tamoxifen is more effective and better tolerated in hormone-responsive patients. Third, other multiple-arm studies have compared LHRHa + chemotherapy with chemotherapy alone. Addition of tamoxifen to goserelin + chemotherapy was shown to improve DFS, and significant benefits in goserelin-treated patients were seen irrespective of use of chemotherapy or tamoxifen. Finally, ongoing trials are addressing the appropriate duration of LHRHa therapy and other unresolved issues. In summary, combined ovarian suppression with adjuvant goserelin and tamoxifen is considered to be at least as effective as chemotherapy in premenopausal breast cancer patients. Published reports have demonstrated that ovarian suppression is a safe means of reducing risk of recurrence in estrogen receptor-positive women and underlined its use as a competitive alternative to chemotherapy in this patient subset.
 ...
PMID:An update on ovarian suppression/ablation. 1701 60


<< Previous 1 2 3 4 5 6 Next >>