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)

A patient with dysphagia and a history of breast cancer 11 yr ago was admitted to the hospital. A tumor presumably originating from the esophagus was detected. It could not be surgically removed and biopsy revealed adenocarcinoma. The patient received radiotherapy and chemotherapy consisting of etoposide, adriamycin, and cisplatin. An unexpectedly good response was achieved and the possibility of metastatic breast cancer was reinvestigated. Biopsy specimens showed positive estrogen and progesterone receptor staining. Tamoxifen treatment was started. The patient is well after 5 yr following relapse. Solitary esophageal metastasis of breast cancer is a rare event, especially after a remission period lasting more than a decade. Dysphagia in breast cancer patients should raise the suspicion of metastatic disease as well as esophageal cancer and benign strictures.
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PMID:Solitary esophageal metastasis of breast cancer after 11 years: a case report. 1248 28

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

Cancer of the breast represents in Tunisia and the most frequent female cancer in the world. Hormonotherapy is one of the main weapons of the medical treatment based on the blockage of hormonal action on the cellular growth. Endocrine therapy remains an essential part of treatment in both adjuvant and metastatic settings and is guided by the presence and degree of expression of estrogen receptor (ER) and progesterone receptor (PgR). Adjuvant 5-years tamoxifen (TAM) is still the standard therapy for postmenopausal ER and/or PgR positive women. In premenopausal women and in adjuvant setting, medical castration by LH-RH analogues plus Tamoxifen in addition to chemotherapy improve the prognosis. All these data arose from the successive meta-analyses done showing a benefit from hormonotherapy for patients with positive HR in term of survival, disease-free survival, loco-regional and distant relapse rate. In metastatic disease, the position of tamoxifen is presently in competition with the third generation antiaromatases that seems to be equally active as tamoxifen opening the way for its use for the future in adjuvant situations.
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PMID:[The status of hormone therapy in breast cancer in 2001?]. 1261 43

1007 cases of female breast cancer patients treated with breast conserving surgery and subsequently irradiation with a median dose of 66 (50-80) Gy including boost with tangential high voltage photon beams. 34.6% (348/1007) received no further therapies, 53.4% (538/1007) Tamoxifen, 26% (262/1007) an adjuvant chemotherapy +/- Tamoxifen. All tumors were classified on the basis of the pathologic-anatomical spreading: 70.7% (712/1007) pT1a-c, 27.4% (276/1007) pT2. 1.9% (19/1007) pT3-4 due to the refusal of mastectomy or an error in the preoperative diagnosis. 32.5% (327/1007) showed proven axillary metastases, of which 26.3% (86/327) > or = 4 LN+. Median age 56 (23-92) years. The local relapse rate after a median follow-up of 70 (12-264) months amounted to 5.9% (59/1007). Distant metastases were registered in 11.5% (116/1007). A total of 8.8% (89/1007) died as consequence of breast cancer, 3.2% (32/1007) of other causes. In 82.6% (816/988) of the pT1/pT2 tumors the resection area had been described. In 29.8% (156/524) in the resected parts there were found rests of tumors. The LRFS falls from 94% to 82% and by remained R1 (26/524) to 47%. Correlation likewise the DMFS, which sanks from 81% to 68% respectively to 63%. We expect a second wave of metastases like the situation by local relapses. Often the R1-resection was connected with other histological high risk factors as multifocality/-centricity, necrosis or vascular invasion. If one divides the patient case sample into a first group with special risk factors (< or = 40 years of age, > or = 4 positive axillary lymph nodes, vascular invasion), and a second which exhibited none of these components, the first group had a 23-26% lower disease free survival rate. Amazing is the fact that, subsequent to a lumpectomy and irradiation, the use or non use of Tamoxifen and/or cytostatics was without proven statistical significance. The evaluation was conceived and implemented more than 20 years ago, and documentation was continuously collected ever since. We're aware of the lack of randomization, but there are less the randomized studies than rather its transformations respectively the daily routine who will decide about life and death. However, evaluations of this data by medical oncologists would, on the one hand, make it possible to better assess the importance of the available data and our results, and, on the other hand, clarify the clinical value of partially and/or completely applied medical treatments.
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PMID:[Correlation of risk factors with the efficacy of applied therapies by breast conserving procedure in breast cancer]. 1272 13

Despite major improvements in the treatment of early-stage breast cancer over the past 15 years, many controversies exist surrounding the optimal adjuvant therapies for these patients. Adjuvant chemotherapy has been demonstrated to reduce recurrence and improve mortality, but questions persist as to what is the optimal regimen and how much adjuvant therapy should be administered. Among the adjuvant chemotherapy issues that remain controversial are the role of the taxanes and the optimal number of adjuvant chemotherapy treatment cycles. In the realm of adjuvant endocrine therapy, the early results of the Anastrozole, Tamoxifen and Combination (ATAC) trial have led to confusion as to how best to treat postmenopausal patients with estrogen receptor-positive, early-stage breast cancer. Clinicians are faced with the decision of choosing between tamoxifen and anastrozole. The enthusiasm for so-called targeted therapies, such as trastuzumab, in patients with metastatic disease, is now being carried over into the adjuvant setting. Multiple clinical trials around the world are evaluating the potential benefit of adding trastuzumab to chemotherapy in patients with HER2-positive, early-stage breast cancer. In the United States, clinicians are faced with many decisions on how to optimally treat patients with early-stage breast cancer. Evidence-based treatment guidelines such as those developed by the National Comprehensive Cancer Network (NCCN) provide a useful algorithm for assisting in making treatment decisions. It is hoped that, in the next few years, the results of ongoing clinical trials now underway will lead to further improvements in the outcome of patients with early-stage breast cancer.
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PMID:Progress in systemic adjuvant therapy of early-stage breast cancer. 1295 80

Tamoxifen has been the gold standard of endocrine therapy for postmenopausal patients with hormone receptor-positive breast cancer for over 20 years. The development of the third-generation aromatase inhibitors anastrozole, letrozole, and exemestane is changing the algorithm for the treatment of the disease. Recent clinical trials have shown that all three third-generation aromatase inhibitors present significant advantages over traditional progestins and aminoglutethimide therapy after tamoxifen failure in postmenopausal women. These new agents are now accepted as first choice for second-line treatment of metastatic disease. Since 2000, phase III trials with anastrozole and letrozole have shown that third-generation aromatase inhibitors are at least as effective as tamoxifen in the first-line treatment of postmenopausal women with hormone receptor-positive or -unknown metastatic breast cancer. The first-line phase III trial of letrozole versus tamoxifen which, unlike the anastrozole trials, was prospectively designed to test superiority of the aromatase inhibitor, showed that this agent was superior to tamoxifen in all assessed outcome measures. A first-line phase III trial of exemestane versus tamoxifen in postmenopausal patients with hormone receptor-positive or -unknown advanced breast cancer is ongoing. The data presented in this article suggest that aromatase inhibitors may replace tamoxifen in the first-line hormonal management of this disease in postmenopausal women.
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PMID:The role of aromatase inhibitors in the treatment of metastatic breast cancer. 1451 35

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.
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PMID:Sequential hormonal therapy for metastatic breast cancer after adjuvant tamoxifen or anastrozole. 1453 31

Tamoxifen has contributed to a dramatic reduction in breast cancer mortality and recent results indicate that aromatase inhibitors may further improve survival in some patients. Nevertheless, a substantial proportion of patients become resistant to treatment. To date, with the exception of estrogen receptor (ER) determination by ligand binding or immunohistochemical techniques, there has been no way of predicting which of several therapies is indicated in particular patients. We describe a novel assay using the adenoviral gene delivery system to assess ER function in breast cancer cells derived directly from patients. The purification and short-term culture of these cells has been recently described by our laboratory. Adenovirus containing an estrogen-regulated beta-galactosidase reporter gene (ERE-lacZ) was constructed and used to test ER activity in breast cancer cells derived from 18 patients with primary and 16 patients with metastatic cancer, under varying treatment schedules. The adenoviral assay enabled ER activity to be readily determined in purified cells from primary breast cancers and secondary sites. Breast cancers cells could be categorized on the basis of ER activity in the absence of ligand, the presence of estrogen or anti-estrogens. In primary breast cancers, our results correlated with ER determination by immunohistochemistry in 78% of cases. In patients who had become resistant to tamoxifen, however, we found some in whom reporter activity was stimulated by tamoxifen and others whose tumors were either still estrogen responsive or completely unresponsive, irrespective of the original ER content. Our findings indicate that this reporter assay could be useful in decisions regarding use of adjuvant endocrine therapies in breast cancer.
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PMID:Reporter gene assay demonstrates functional differences in estrogen receptor activity in purified breast cancer cells: a pilot study. 1456 18

Tamoxifen is commonly used in the management of patients with breast cancer because of its anti-oestrogenic effects to the breasts. However, tamoxifen acts as an oestrogen agonist on the endometrium increasing the incidence of endometrial polyps, hyperplasia and cancer. In addition, it may be possible that tamoxifen increases the occurrence of uterine body tumours. We describe a rare case of a large endometrial polyp with sarcomatous stromal components in a 73-year-old breast cancer patient treated daily with 20 mg of tamoxifen for four years. The glands of the polyp were lined by benign appearing epithelium. The polyp was twisted and protruded from a dilated cervix at the entrance of the vagina. The patient was treated by removal of the polyp and dilatation and curretage. A postoperative computed tomography scan showed many focal hypodense lesions in the hepatic lobes with a well-defined profile suggestive of metastatic disease and the patient was referred for combined chemotherapy. In conclusion, a case of a mesenchymal malignant neoplasm arising in the uterus of a breast cancer patient treated with tamoxifen is reported and its clinical, histological and immunohistochemical features are discussed. Also, the international literature is reviewed.
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PMID:Large endometrial polyp with sarcomatous stromal components following long-term tamoxifen treatment for breast cancer: a case report and review of the literature. 1465 6

Breast cancer represents a major health problem, with more than 1,000,000 new cases and 370,000 deaths yearly worldwide. In the last decade, in spite of an increasing incidence, breast cancer mortality has been declining in the majority of developed countries. This is the combined result of better education, widespread screening programmes and more efficacious adjuvant treatments. Better knowledge of breast cancer biology now allows the cosmetic, physical and psychological consequences of radical mastectomy to be spared in the majority of breast cancer patients. Use of the sentinel node technique is rapidly expanding and this will further reduce the extent and the consequences of surgery. Several clinico-pathological factors are used to discriminate between patients at low (<10%), average (10-40%) and high risk of relapse. Nodal status, tumour size, tumour grade and age are accepted universally as important factors to define risk categories. Newer factors such as uPA/PAI-1, HERer2-neu, proliferative indices and gene expression profile are promising and will allow better discrimination between patients at different risk. Endocrine manipulation with tamoxifen, ovarian ablation or both is the preferred option in the case of endocrine-responsive tumours. Tamoxifen administered for 5 years is the standard treatment for postmenopausal patients; tamoxifen plus ovarian ablation is more effective than tamoxifen alone for premenopausal women. Recent data demonstrate that, for postmenopausal patients, the aromatase inhibitors are superior to tamoxifen, with a different safety profile. At present, anastrozole can be used in the adjuvant setting in cases of tamoxifen intolerance or toxicity. Chemotherapy is the treatment of choice for steroid receptor-negative tumours. Polychemotherapy is superior to single agents and anthracycline-containing regimens are superior to CMF. Six courses of FEC or FAC or the sequential administration of four doses of anthracycline followed by four of CMF are the recommended regimens. New regimens including the taxanes have produced a further improvement in risk reduction and are reasonable therapeutic options. The taxanes have been approved for adjuvant therapy in the USA, while European approval is pending. Combined endocrine-chemotherapy is the standard adjuvant treatment in high-risk patients with endocrine-responsive tumours. Endocrine manipulation is usually administered after completion of the chemotherapy programme. For HER2-neu overexpressing tumours, several rapidly accruing trials are exploring the potential additive effect of trastuzumab, a monoclonal antibody directed against the extramembrane portion of the HER2 receptor. Primary chemotherapy is increasingly used in the treatment of locally advanced and operable breast cancer, with increased rates of breast-conserving surgery. A proportion of patients achieve a pathological complete response and these patients have significantly better long-term outcomes. Twenty-five to forty percent of breast cancer patients develop distant metastases. At this stage the disease is incurable; however, treatments can assure a significant prolongation of survival, symptomatic control and maintenance of quality of life. In the case of hormone receptor positivity and in the absence of visceral, life-threatening disease, endocrine manipulation is the treatment of choice. Active treatments include tamoxifen, ovarian ablation, aromatase inhibitors, pure anti-oestrogens and progestins. Aromatase inhibitors are the most active agents, but the choice and the sequence of endocrine therapies are also dictated by prior adjuvant treatment. Chemotherapy has to be preferred in cases of receptor-negative tumours, acquired resistance to hormones and aggressive visceral disease. Combination regimens are usually associated with higher response rates and sometimes survival prolongation, and this approach should be recommended in young patients with good performance status and visceral disease. On the other hand, single agents have a better tolerability profile and should be tand should be the treatment of choice when a careful balance between activity and tolerability is needed. For HER2-neu positive tumours, the combination of trastuzumab and chemotherapy is significantly superior to chemotherapy alone in terms of both response rates and survival. Other useful palliative treatments include bisphosphonates for the control of metastatic bone disease and radiotherapy for painful bone lesions or local relapses.
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PMID:The curability of breast cancer and the treatment of advanced disease. 1510 48


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