Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

More than 40,000 women in the United States die each year from metastatic breast cancer. Elucidation of HER2 and its role in malignant transformation has helped define a subset of aggressive breast cancer that may be relatively resistant to non-anthracycline-based therapies and hormonal agents, but responds to targeted molecular therapy. Trastuzumab, an antibody against HER2, has proven effective as single agent therapy in women with HER2 overexpressed metastatic breast cancer. Moreover, in combination with chemotherapy, trastuzumab has been shown to delay disease progression and improve overall survival for women with HER2-positive advanced breast cancer. The combination of chemotherapy and trastuzumab is emerging as a standard of care in women with HER2 overexpressed metastatic breast cancer. Several combination regimens using trastuzumab with taxanes, vinca alkaloids, or platinum compounds have demonstrated efficacy in first- and second-line treatment settings. However, the development of anthracycline-based combinations has been limited by concerns of related cardiotoxicity. Newer multi-agent regimens are in development. The optimal combination, duration, and sequence of trastuzumab therapy remain unknown in patients with HER2-positive metastatic disease. The role of continuing treatment after disease progression is also unclear. Evidence from some retrospective analyses suggest HER2-positive tumors are relatively resistant to tamoxifen and perhaps more responsive to aromatase inhibitors, although such data are inconclusive. HER2 status should not be used routinely for clinical decision making regarding hormonal therapy options. Several ongoing trials are attempting to address these and other issues related to HER2 testing to select the most appropriate candidates for these emerging therapies. While many questions remain, the treatment of HER2 overexpressing metastatic breast cancer is rapidly evolving, and represents a new approach to treatment in oncology.
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PMID:HER2 overexpressing metastatic breast cancer. 1205 79

The lifetime risk of breast cancer in women is 1 in 8, with an increasing incidence in each decade of life after age 40. Breast cancer is considered curable with detection and treatment during Stages I and II, but disease-free survival drops in Stage III and is essentially zero in Stage IV. Breast-conserving surgical removal of tumors has been the standard of care for primary local therapy for more than a decade. For prevention of recurrence, tamoxifen is recommended in dosages of 20 mg/day for 5 years. The aromatase inhibitors are now considered first-line therapy in metastatic disease, and use of the monoclonal antibody trastuzumab has increased 5-year survival rates.
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PMID:Developments in breast cancer therapy. 1229 44

A 63-year-old postmenopausal woman was referred to our hospital for treatment of ER positive advanced breast cancer. The patient had lung and pleural metastases with pleural effusion from breast cancer. She was treated with anastrozole, a 3rd-generation aromatase inhibitor, which brought about a marked regression of the lung tumor, and disappearance of pleural effusion. The patient experienced no adverse effects with this therapy. Anastrozole therapy is a useful treatment for postmenopausal women with ER positive advanced breast cancer.
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PMID:[Advanced breast cancer with lung and pleural metastases responsive to anastrozole--a case report]. 1235 46

The systemic treatment of breast cancer is a moving target, reflected by the continuous update of treatment guidelines. Chemotherapy regimens, including the adjuvant role of taxanes and preoperative systemic therapy, continue to be optimized. A major challenge facing researchers and clinicians is how to improve the therapeutic index of present and future therapies, identify patients most likely to benefit from the proposed intervention, and avoid treating those who would be exposed to potential toxicities with minimal gain. Anti-estrogens are a prime example of a targeted therapy with a high therapeutic index. Data are now available on aromatase inhibitors in the adjuvant setting and pure antiestrogens in metastatic disease. The role of targeted antihuman epidermal growth factor receptor 2 therapy in the adjuvant setting is being actively investigated, but this is complicated by the inadequate standardization of human epidermal growth factor receptor 2 expression assays used in clinical practice. A long overdue revision of the breast cancer staging system becomes effective in January 2003, bringing it more in line with current standards of care and facilitating data collection for future outcome analysis of therapeutic interventions. These and other important developments since 2001 are examined in this review.
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PMID:Systemic therapy. 1240 49

The use of drugs, which inhibit estrogen biosynthesis, is an attractive treatment for postmenopausal women with hormone-dependent breast cancer. Estrogen deprivation is most specifically achieved using inhibitors which block the last stage in the biosynthetic sequence, i.e., the conversion of androgens to estrogens by the aromatase enzyme. Recently, a new generation of aromatase inhibitors has been developed. Among these, letrozole (Femara) appears to be the most potent. When given orally in milligram amounts per day to postmenopausal women, the drug almost totally inhibits peripheral aromatase and causes a marked reduction in circulating estrogens to levels that are often undetectable in conventional assays. Similarly, neoadjuvant studies demonstrate that letrozole substantially inhibits aromatase activity in both malignant and nonmalignant breast tissues, and markedly suppresses endogenous estrogens within the breast cancers. These studies also illustrate anti-estrogenic and anti-proliferative effects of letrozole in estrogen receptor (ER)-rich tumors. Thus, tumor expression of progesterone receptors and the cell-cycle marker Ki67 is significantly and consistently reduced with treatment. Additionally, clear pathological responses as evidenced by decreased cellularity and increased fibrosis are seen in the majority of cases. These results translated into clinical benefit in a series of 24 breast cancers treated neoadjuvantly with letrozole (either 2.5 or 10 mg): tumor volume reductions > 25% were observed in 23 women, and > 50% reductions in 18 patients. Pathological and clinical effects are seen much more consistently than with tamoxifen. Thus, in a multicenter randomized trial of letrozole vs. tamoxifen (PE 024), clinical study outcomes were superior for letrozole in comparison with tamoxifen with regard to overall tumor response and an increase in the proportion of patients treated by breast conserving surgery. Letrozole has also been used in advanced breast cancer, both as second-line hormone treatment following tamoxifen failure, and more recently as first-line therapy. Trials of second-line treatment in which letrozole has been compared with either older aromatase inhibitors or progestins have shown equivalent or superior clinical activity and improved tolerability favoring letrozole. In first-line comparison with tamoxifen in metastatic disease, a phase III trial of over 900 postmenopausal women showed letrozole to be significantly better than tamoxifen in terms of overall tumor response rates, clinical benefit, and time to treatment failure. In summary, letrozole is an exceptionally potent and specific endocrine agent. In patients with ER-rich tumors, high rates of pathological and clinical response have been documented, and large phase III trials against established treatments such as tamoxifen and progestin suggest superior (or at least equivalent) clinical efficacy. Letrozole is a drug of immense potential and in the future is likely to occupy a central role in the management of postmenopausal women with hormone-dependent breast cancer.
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PMID:Anti-tumor effects of letrozole. 1244 45

Endocrine therapy remains an important approach to the treatment of metastatic breast cancer because of its effectiveness and excellent tolerability. In the last 10 years, a number of new endocrine therapies have been introduced. These include the luteinizing hormone-releasing hormone agonists, which produce menopausal changes in premenopausal women; the aromatase inhibitors, which prevent production of estrogen in postmenopausal women; and the estrogen receptor down-regulator fulvestrant (Faslodex), which is effective in postmenopausal women whose tumors have progressed following response to other selective estrogen receptor modulators. The endocrine cascade for the treatment of premenopausal women with metastatic disease now involves the concurrent or sequential combination of a luteinizing hormone-releasing hormone analogue and tamoxifen, whereas the cascade for the treatment of postmenopausal women can begin with tamoxifen followed by an aromatase inhibitor or with an aromatase inhibitor followed by tamoxifen. The optimal cascade following the use of an aromatase inhibitor and tamoxifen in postmenopausal women remains unclear, but fulvestrant and megestrol acetate or the use of an aromatase inactivator (exemestane) following an aromatase inhibitor are all available options with some activity. Over the next few years, clinical trials will clarify the optimal sequence of endocrine therapy for postmenopausal women. The use of estrogen and progesterone receptor status to select for endocrine therapy is undeniably crucial. HER2/neu overexpression may also predict response to endocrine therapy, but this remains controversial.
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PMID:Endocrine therapy of advanced disease: analysis and implications of the existing data. 1253 1

In the United States, three third-generation aromatase inhibitors are available commercially: anastrozole, letrozole, and exemestane. Anastrozole and letrozole are nonsteroidal agents, whereas exemestane is a steroid. The three agents differ in terms of structure and metabolic products and in the degree to which they suppress aromatase activity. The clinical significance of these differences is unclear. All three of the agents have been found to be equivalent or superior to megesterol acetate as a second-line therapy for metastatic breast cancer. In the first-line setting, large Phase III trials have demonstrated that anastrozole and letrozole are equivalent or superior to tamoxifen in women with metastatic disease. Multiple trials with widely varying study designs have been launched in the adjuvant setting comparing the aromatase inhibitors to tamoxifen. Early results from the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial suggest a small but statistically significant improvement in disease-free survival for anastrozole compared with tamoxifen, but further follow-up is needed. This article explores the efficacy and tolerability of the aromatase inhibitors in both the metastatic and the adjuvant settings.
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PMID:Clinical differences among the aromatase inhibitors. 1253 3

Treatments for men with breast cancer are based largely on accepted regimens for women with the disease. Surgical treatment of the primary tumor should be a mastectomy. Lymph node assessment can be done by conventional axillary node dissection or, similar to selected women with small primary tumors, by sentinel node dissection. Decisions regarding adjuvant systemic treatment should be made on the same basis as for women. Axillary node status, tumor size, hormone receptor status, and the health of the patient are important considerations in determining what adjuvant treatment is offered. The role of radiation after mastectomy in men is not well defined, but radiation should be used in patients at high risk for local recurrence. For patients with metastatic disease, treatment is based on the hormone receptor status of the tumor and is similar to the treatment for women. Because most men with breast cancer have hormone receptor-positive disease, hormonal therapy is a mainstay of treatment and tamoxifen remains the front-line drug of choice, although the latest generation of aromatase inhibitors have supplanted tamoxifen as a first-line therapy for women. As a second-line hormonal therapy for men, orchiectomy or a luteinizing hormone-releasing hormone agonist with or without an antiandrogen are reasonable alternatives. There are no reports regarding the use of the antiestrogen fulvestrant in men, but its mechanism of action and efficacy in women suggest that it will be a useful agent in hormone receptor-positive male breast cancer. For men with hormone-resistant disease, palliative chemotherapy with the same agents used for treatment of women with breast cancer is appropriate.
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PMID:Male breast cancer. 1259 42

The efficacy of fulvestrant (Faslodex), a novel oestrogen receptor (ER) antagonist that downregulates the ER and has no known agonist effects, was compared with the aromatase inhibitor anastrozole (Arimidex) for the second-line treatment of advanced breast cancer in postmenopausal women with visceral and non-visceral metastases. Assessment was by means of a retrospective subgroup analysis of combined data from two randomised, phase III trials. Objective response (OR) rates were similar in patients treated with fulvestrant and anastrozole, respectively (21.9% versus 19.3%-patients with no visceral metastases; 15.7% versus 13.2%-all of the patients with visceral metastases; 18.8% versus 14.0%-patients with visceral metastases only). The proportion of patients with clinical benefit (CB) was also similar between treatments and between subgroups with and without visceral disease. Fulvestrant is at least as effective as anastrozole, providing a valuable treatment option for advanced breast cancer in postmenopausal women with visceral metastases who have failed on prior endocrine therapy.
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PMID:Fulvestrant (Faslodex) versus anastrozole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and non-visceral metastases: combined results from two multicentre trials. 1276 10

Modern treatment of cancer of the breast is based on established prognostic factors (patient age, receptor status, tumor size, lymph node involvement, tumor grading), and thus takes the patient's individual risk profile into account. In addition to the antiestrogen, tamoxifen, new hormonal preparations, such as the aromatase inhibitors, hold out promise of improved results from adjuvant treatment in elderly women. In premenopausal women, additional hormone blockade by means of GnRH analogs is of advantage. Neoadjuvant (preoperative) chemotherapy protocols will enable rapid evaluation of new therapeutic options. When metastases have developed, treatment with hormonal drugs is indicated in the case of slowly progressing disease (low risk), while clinically progressive metastasization (high risk) requires cytostatic chemotherapy. Here, studies involving more recent substances with improved tolerability, and tumor-specific antibodies, confirm an improvement in the prognosis. The concentration of drug treatment in interdisciplinary centers is a necessary element of quality assurance and therapeutic optimization.
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PMID:[Hormone therapy, chemotherapy and immunotherapy in breast carcinoma. The best strategy for your patient]. 1286 98


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