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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hormone therapy is the most important systemic treatment of hormone receptor-positive breast cancer at all stages. Selective oestrogen receptor modulators (SERMs), such as tamoxifen, the mainstay of hormone receptor positive breast cancer manipulation for many years, are limited by their agonist actions. Oestrogen-like activity of these drugs may stimulate cancer growth such as in the endometrium and is a mechanism of resistance in breast cancer. Fulvestrant, the first of a new class of drugs, an oestrogen receptor down regulator, may have advantages over tamoxifen in the treatment of oestrogen-dependent disease. The pre-clinical development and early clinical data of fulvestrant are reviewed. Fulvestrant was as effective as the aromatase inhibitor anastrazole in second-line advanced breast cancer. The phase III trial of fulvestrant versus tamoxifen, as first-line treatment for metastatic breast cancer, has completed accrual and is maturing. Fulvestrant has useful activity against breast cancer as well as a favourable side-effect profile and is likely to represent a useful addition to the fight against hormone dependent breast cancer. Its place will be better defined by ongoing clinical trials.
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PMID:Fulvestrant: a review of its development, pre-clinical and clinical data. 1207 16

During 1986-1987, 192 women aged 26-86 with invasive breast cancer were treated with radiotherapy, hormonotherapy, and chemotherapy and then underwent modified radical mastectomy or wide local excision at Luis Castelazo Ayala Hospital of Obstetrics and Gynecology of the Mexican Social Security Institute in Mexico City. At diagnosis, metastatic bone surveys and bone scans showed that no one had distant metastasis. The physicians used incisional biopsy to determine the type of breast carcinoma (infiltrating ductal carcinoma [IDC] and infiltrating lobular carcinoma [ILC]). The researchers aimed to identify prognostic factors in primary breast cancer. 156 patients (81.3%) and 36 patients (18.7%) had IDC and ILC, respectively. Among women with IDC, axillary nodes were involved in 23.5% of premenopausal women and in 23% of postmenopausal women. 83.8% of all patients with IDC and 52.3% of IDC patients aged at least 50 had clinical stage III disease. Among women with ILC, axillary nodes were involved in 19.4% of premenopausal women and in 19.4% of postmenopausal women. 70% of all patients with ILC and 84.6% of ILC patients aged at least 50 had clinical stage III disease. All the patients had advanced breast cancer (i.e., clinical stage II and III). Some tumors were only estrogen receptor types, while others were only progesterone receptor types. Some tumors were even both receptor types, while another category had neither steroid hormone receptor. Survival rates for metastatic and non-metastatic breast cancer was greater among postmenopausal women than premenopausal women (32.7% vs. 14.8% and 21.8% vs. 12.8% for ICD and 19.4% vs. 8.4% and 30.5% vs. 13.9% for ILC, respectively). These findings suggest that axillary node status, status of estrogen and progesterone receptors, and menstrual status were important prognostic factors of breast cancer.
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PMID:Infiltrating ductal / lobular carcinoma: an evaluation of prognostic factors in primary breast cancer. 1232 22

A wide range of endocrine therapies has demonstrated activity in the treatment of hormone receptor-positive metastatic breast cancer and sequential tumor responses to sequential hormonal therapies are common. However, the optimal sequence of the hormonal therapies has not yet been determined. The selection of endocrine therapies in women with hormone receptor-positive breast cancer is strongly influenced by the menopausal status of the patient. For premenopausal women, tamoxifen alone or combined with ovarian suppression using a luteinizing hormone-releasing hormone (LHRH) agonist - such as goserelin or leuprolide - is an appropriate first-line hormonal therapy. Ovarian ablation or megestrol acetate is an appropriate second-line hormonal therapy for premenopausal women treated with tamoxifen as first-line therapy, or ovarian ablation plus an aromatase inhibitor (AI) or megestrol acetate for women treated with first-line tamoxifen plus an LHRH agonist. For postmenopausal women, the non-steroidal AIs anastrozole and letrozole now represent the preferred first-line hormonal treatment for metastatic breast cancer, based upon both efficacy and toxicity considerations. For second-line therapy in postmenopausal women, a number of options now exist, including tamoxifen, the steroidal AI exemestane, and the new agent fulvestrant. Fulvestrant, a novel estrogen receptor (ER) antagonist that downregulates the ER and has no known agonist effects, has been demonstrated to be at least as effective as anastrozole in postmenopausal women whose tumors progress on tamoxifen. The establishment of the optimal sequence of the endocrine therapies should offer significant benefits to women with hormone-sensitive metastatic breast cancer.
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PMID:Sequencing of endocrine therapies in breast cancer--integration of recent data. 1235 21

Over recent decades, there have been significant advances in the variety of therapies available for the treatment of breast cancer. These developments have produced many improvements in patient response and survival. In primary breast cancer, chemotherapy has been shown to provide significant long-term benefits in the prevention of recurrence and prolongation of patient survival. Similar benefits have been documented for various hormonal manipulations in patients with steroid hormone receptor-positive tumors. Work is ongoing to establish the optimal type and combination of endocrine therapy and chemotherapies. In endocrine-sensitive, metastatic breast cancer, the sequential use of endocrine therapies is considered the optimal strategy, and studies are underway to integrate novel endocrine agents into the management of this disease. For patients with high-risk disease, chemotherapy agents (such as the anthracyclines and taxanes) have exhibited survival benefits, as has the new anticancer monoclonal antibody, trastuzumab. As the number of effective therapies increases, it becomes increasingly important to be able to select the correct combination or sequence of agents. To this end, an important challenge in the development of breast cancer therapy is to use the molecular characterization of the disease as an opportunity to establish and exploit markers of chemosensitivity and resistance, leading eventually to the individualization of therapy for breast cancer patients and to the targeted use of the most appropriate therapies.
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PMID:The status of breast cancer management: challenges and opportunities. 1235 25

Patients with hormone-sensitive breast cancer who have responded to tamoxifen may receive additional benefit from a second endocrine agent following progression or relapse after tamoxifen therapy. Fulvestrant (Faslodex((R)), ICI 182780, AstraZeneca Pharmaceuticals; Wilmington, Delaware) is a selective antagonist of estrogen designed to have no estrogenic effects. Lack of aqueous solubility led to the development of a parenteral formulation for monthly intramuscular administration. Fulvestrant has been shown to inhibit the proliferative effects of estrogen on sensitive tissues in vitro and in vivo, and is without apparent measurable estrogenic activity. The data upon which marketing approval for fulvestrant was based are summarized below. Eight hundred fifty-one postmenopausal women with advanced breast cancer were enrolled in two phase III studies, 400 in a North American double-blind study and 451 in a European open-label study, comparing the efficacy and safety of fulvestrant with anastrozole. Four hundred twenty-eight patients were randomized to receive fulvestrant 250 mg monthly by intramuscular injection and 423 patients were to receive anastrozole 1 mg daily. Patients were considered hormone sensitive either by receptor status or previous response to endocrine therapy. Over 96% of patients had previously received tamoxifen, either in the adjuvant setting or as treatment for metastatic disease. The primary study end points were response rate and time to progression. Response rates for patients treated with fulvestrant were 17% and 20% in the North American and European trials, respectively, compared with 17% and 15% in the anastrozole treatment arms. There were no statistically significant differences in response rates, time to progression, or survival between treatment arms in either study. The most common adverse events attributed to the treatment (>10%) were injection-site reactions and hot flashes. Common events (1%-10%) included asthenia, headache, and gastrointestinal disturbances (nausea, vomiting, and diarrhea), as well as rash and urinary tract infections. A small increase in joint disorders was reported in the anastrozole-treated patients. On April 25, 2002, fulvestrant 250 mg by monthly intramuscular injection was approved by the U.S. Food and Drug Administration for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Approval was based on similarity of response rates and time to progression between fulvestrant and anastrozole.
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PMID:FDA drug approval summaries: fulvestrant. 1249 Jul 35

Interleukin-6 (IL-6) is a multifunctional cytokine produced by macrophages, T cells, B cells, endothelial cells and tumour cells. Interleukin-6 is able to promote tumour growth by upregulating anti-apoptotic and angiogenic proteins in tumour cells. In murine models it has been demonstrated that antibodies against IL-6 diminish tumour growth. Several reports have highlighted the prognostic importance of IL-6 in e.g., prostate and colon cancer. We addressed prospectively the prognostic significance of serum IL-6 (sIL-6), measured at diagnosis of metastasis, in 96 unselected and consecutive patients with progressive metastatic breast cancer before the initiation of systemic therapy. The median sIL-6 value for the breast cancer population was 6.6 +/- 2.1 pg/ml. Patients with 2 or more metastatic sites had higher sIL-6 values compared to those with only 1 metastatic site (respectively 8.15 +/- 1.7 pg/ml and 3.06 +/- 6.6 pg/ml; p < 0.001). Patients with liver metastasis (8.3 +/- 2.4 pg/ml), with pleural effusions (10.65 +/- 9.9 pg/ml) and with dominant visceral disease (8.15 +/- 3.3 pg/ml) had significantly higher values compared to those without liver metastases (4.5 +/- 3.4 pg/ml; p = 0.001), without pleural effusions (5.45 +/- 1.5 pg/ml; p = 0.0077) and with dominant bone disease (4.5 +/- 1.4 pg/ml; p = 0.007) respectively. No correlation between sIL-6 and age, menopausal status, performance status, tumour grade, body-mass index, histology and hormone receptor status was found. Multivariate analysis showed that high levels of serum IL-6 have independent prognostic value. We conclude that circulating IL-6 is associated with worse survival in patients with metastatic breast cancer and is correlated with the extent of disease.
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PMID:Circulating interleukin-6 predicts survival in patients with metastatic breast cancer. 1249 72

Since its introduction more than 30 years ago, tamoxifen has been the most widely used endocrine therapy for the treatment of women with advanced breast cancer. More recently, a number of alternative endocrine treatments have been developed, including several selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs) and, most recently, fulvestrant ('Faslodex'). Fulvestrant is an estrogen receptor (ER) antagonist, which, unlike the SERMs, has no known agonist (estrogenic) effect and downregulates the ER protein. Tamoxifen is effective and well tolerated, although the non-steroidal AIs, anastrozole and letrozole, are more effective treatments for advanced disease than tamoxifen. Fulvestrant has recently gained US Food and Drug Administration approval for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. In two global phase III clinical trials fulvestrant was at least as effective and as equally well tolerated as anastrozole for the treatment of postmenopausal women with advanced and metastatic breast cancer. In a retrospective analysis of the combined data from these trials, mean duration of response was significantly greater for fulvestrant compared with anastrozole. These new hormonal treatments expand the choice of endocrine therapy for women with advanced breast cancer and offer new options for sequencing and combining treatments.
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PMID:Fulvestrant ('Faslodex')--a new treatment option for patients progressing on prior endocrine therapy. 1254 3

The role of hormonal therapy for the treatment of patients with early stage breast cancer has been evaluated in many studies. The results of these studies establish tamoxifen as the gold standard of hormonal therapy for the adjuvant treatment of hormone receptor-positive invasive breast cancer in pre- and postmenopausal women. Studies show tamoxifen reduces the risk of invasive breast cancer in women at increased risk for the disease, including women with ductal carcinoma in situ. Tamoxifen has adverse effects such as hot flashes, increased risk of uterine cancer in postmenopausal women, and rare occurrence of thromboembolic disease. Despite the multiple therapeutic roles of tamoxifen, alternatives are needed. Aromatase inhibitors (AI) are drugs with antiestrogenic activity. AIs function by inhibiting the peripheral conversion of adrenally synthesized androstenedione to estradiol through inhibition of the aromatase enzyme. AIs do not suppress estradiol synthesis by the ovary adequately. Therefore, AIs are effective in reducing circulating estradiol levels in postmenopausal women, but not premenopausal women. Selective nonsteroidal AIs, including anastrozole (Arimidex; AstraZeneca, Wilmington, DE) and letrozole (Femara; Novartis, East Hanover, NJ), and the steroidal AI exemestane (Aromasin; Pharmacia, Peapack, NJ) have been associated with increased specificity and improved therapeutic index compared to nonselective AIs such as aminoglutethamide. Nonsteroidal and steroidal AIs have demonstrated to be superior to megestrol acetate in second-line therapy of postmenopausal women with metastatic breast cancer, and selective nonsteroidal AIs have shown to be superior to tamoxifen in first-line therapy of postmenopausal women with metastatic breast cancer. The ATAC (Arimidex, tamoxifen, alone, or in combination) trial is the only published randomized trial comparing the efficacy of an AI to tamoxifen for the adjuvant treatment of women with early breast cancer. This large study showed that at a median follow-up time of 33 months, anastrozole alone results in significant improvement in disease-free survival rates, reduction in contralateral breast cancers, and increased tolerability, compared to tamoxifen in postmenopausal women. Although the long-term effects of AIs are not known, the early positive results of the ATAC trial led to the approval of anastrozole by the US Food and Drug Administration for use as adjuvant hormonal therapy for postmenopausal women with hormone receptor-positive invasive breast cancer. Thus, there is an alternative to tamoxifen for postmenopausal women with relative/absolute contraindications to tamoxifen use or patients who choose not to take tamoxifen because of its side-effect profile. New AIs may challenge the position of tamoxifen as the gold standard for the treatment of early stage breast cancer in postmenopausal women.
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PMID:The role of aromatase inhibitors in early breast cancer. 1259 39

For women who develop hormone-refractory metastatic breast cancer, or who have breast cancers that are not estrogen-dependent (hormone receptor-negative), treatment with chemotherapy is the best option. Mitomycin (Mutamycin) and irinotecan (CPT-11, Camptosar) have marginal activity in breast cancer. However, the sequential administration of mitomycin and irinotecan appears to have synergism in preclinical studies, as mitomycin upregulates the level of topoisomerase I, the target of irinotecan. A phase I clinical trial of pharmacologically based sequential administration of mitomycin on day 1 followed by irinotecan on days 2 and 8 was performed in previously treated solid tumor patients. In five heavily pretreated women with breast cancer, one patient had a complete response, one patient had a partial response, and one patient had stable disease. Upregulation of topoisomerase I gene expression in peripheral blood mononuclear cells was observed in two of the responding patients. A phase II trial of mitomycin followed by irinotecan in women with previously treated metastatic, inflammatory, or locally advanced breast cancer is currently ongoing.
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PMID:Rationale for mitomycin and irinotecan use in advanced breast cancer. 1280 Jun 2

Randomized clinical trials have established the role of third-generation aromatase inhibitors (AIs) (letrozole, anastrozole, and exemestane) as standard treatment for patients with hormone-sensitive metastatic breast cancer who have experienced disease progression with antiestrogen therapy. Significant gains in clinical efficacy and improved tolerability over progestins (megestrol acetate) and the first-generation AI aminoglutethimide have positioned these agents above previous therapies. Estrogen receptor (ER) status remains the best predictive determinant of endocrine response, and further randomized trials with properly selected patient populations may distinguish individual AIs within this class. A recently completed, randomized, head-to-head phase III trial of letrozole versus anastrozole as second-line endocrine therapy demonstrated a significant difference in objective response rate for letrozole compared with anastrozole (19% versus 12%, respectively; P = 0.014), with similar time to progression. The improved efficacy and safety of AIs as second-line endocrine therapies has spawned trials of their use as first-line endocrine therapy versus tamoxifen for patients with metastatic breast cancer. Based on favorable results from these trials, letrozole and anastrozole have also been approved for use as first-line treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer.
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PMID:A comparison of the efficacy of aromatase inhibitors in second-line treatment of metastatic breast cancer. 1290 72


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