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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This commentary evaluates progress made in the treatment of breast cancer during the twentieth century. Most of the period from 1900 to 1970 was governed by the 'non-science' of anecdotalism and classical inductivism and was marked by the absence of a scientific gestalt. In keeping with the Halstedian concept that breast cancer was a local disease that spread throughout the body by contiguous extension and could be cured by more expansive surgery, the disease was treated with radical surgery. In 1950, however, a new era of enlightenment began to emerge. The awareness that there was a scientific process in which hypotheses generated from laboratory and clinical investigation could be tested by means of randomised clinical trials was a seminal advance, as were findings from studies that laid the groundwork for the modern era of steroid hormone action, including identification of oestrogen receptors. Expanding knowledge regarding tumour cell kinetics, tumour heterogeneity, and technological advances related to mammography and radiation therapy were also to play a role in making possible the advances in therapy that were subsequently to occur. In the past 30 years, as a result of laboratory and clinical investigation, the Halstedian thesis of cancer surgery was displaced by an alternative hypothesis that was supported by findings from subsequent clinical trials. A new paradigm governed surgery for breast cancer, and lumpectomy followed by radiation therapy became accepted practice. A second paradigm that governed the use of adjuvant systemic therapy arose as a result of laboratory and clinical investigation. Treating patients who were free of identifiable metastatic disease with systemic adjuvant therapy because some of them might develop distant disease in the future was a revolutionary departure from prior treatment strategy and became a new exemplar. Not only did the chemotherapy favourably alter the outcome of breast cancer patients, but the anti-oestrogen tamoxifen benefited patients with all stages of the disease. Tamoxifen also reduced the incidence of contralateral breast cancer, as well as tumour in the ipsilateral breast following lumpectomy. The use of preoperative therapy was also found to enhance breast-conserving surgery in women with large tumours, although its value in other circumstances is still being defined. The observation that, as a result of tamoxifen administration, invasive and non-invasive breast cancers can be prevented in women who are at increased risk for such tumours, and the finding that pathological entities such as atypical hyperplasia, lobular carcinoma in situ (LCIS) and intraductal carcinoma (DCIS) can identify women who should be considered candidates for tamoxifen serve as a fitting capstone to the accomplishments of the twentieth century. Breast cancer prevention has now become a reality. Unfortunately, a variety of circumstances have arisen as the result of advances in the understanding and treatment of breast cancer over the last 30 years that threaten to nullify the progress that has been achieved. This distressing phenomenon may be reviewed as a 'paradox of accomplishment'. The numerous uncertainties, issues and questions that have arisen following the report of each advance in treatment, the surfeit of new information that has not yet been integrated into treatment strategies, the undesirable consequences of enhanced tumour detection, a reversion to Halstedianism and anecdotalism, and the uncertainty of therapeutic decision making resulting from the demonstration of small but statistically significant benefits, particularly in patients with good prognosis, need to be addressed. Inappropriate interpretation of those circumstances threatens to deny women with breast cancer and those at high risk for the disease the opportunity to benefit from treatments that have been proven to be of worth. Perhaps the most important accomplishment of the twentieth century relates to the change in the pro
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PMID:From Halsted to prevention and beyond: advances in the management of breast cancer during the twentieth century. 1071 Dec 39

Liarozole is an imidazole compound that inhibits enzymes involved in steroid hormone aromatisation and retinoid metabolism. The IDBBC branch of the EORTC has performed a series of phase II studies of the agent in four groups of postmenopausal women with metastatic breast cancer. This paper reports the results of the first two groups: 'Chemotherapy Resistant' (unrestricted ER status, 1 or 2 prior chemotherapy regimens, 0-2 prior hormonal therapies) and 'Potentially Hormone Sensitive' (ER positive or unknown, 1 or 2 prior hormonal therapies with a substantial disease free interval or progression free survival, and no history of chemotherapy for metastatic disease). Liarozole was administered at 150-300 mg orally bid. The objective response rate was 12% in the 'Chemotherapy Resistant' group (n = 34), and 22% in the 'Potentially Hormone Sensitive' group (n = 37), with median response durations of 9 and 14 months, respectively. Median time to treatment failure was only 2 months in both groups, due largely to the significant percentage (24%) of patients who ceased treatment following excessive mucocutaneous and gastrointestinal toxicity. This adverse event profile will limit its use in breast cancer. Results of the 'ER negative' and 'Tamoxifen Refractory' groups will be reported in a future paper.
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PMID:EORTC 10941: A phase II study of liarozole in postmenopausal patients with 'chemotherapy-resistant' or 'potentially hormone sensitive' metastatic breast cancer. 1084 81

The assessment of angiogenesis in breast cancer is of importance as a key indicator of survival and response to therapy. Circulating vascular endothelial growth factor (VEGF) measurements may provide a less subjective analysis than microvessel density (MVD) or immunohistochemical analysis of VEGF expression; however, most studies have used serum, which is now known to largely reflect platelet-derived VEGF concentrations. This study examined for the first time both plasma (VEGFp) and serum (VEGFs) VEGF concentrations in 201 blood samples from pre- and postmenopausal healthy controls and from patients with benign breast disease, localized breast cancer, breast cancer in remission, or metastatic breast cancer and related these to other clinicopathological markers. VEGFp but not VEGFs concentrations of patients with localized disease were significantly elevated compared with normal controls (P = 0.016). Patients with metastatic disease had higher VEGFp and VEGFs levels than normal controls (P < 0.001, P = 0.044 respectively), and higher VEGFp, but not VEGFs, than patients with benign disease (P = 0.009) and patients with localized disease (P = 0.004). However, the highest VEGFp and VEGFs concentrations were seen in patients in remission compared with normal controls (P < 0.001 and P = 0.008, respectively). VEGFp concentrations in patients in remission were also higher than in patients with benign disease (P = 0.01) or patients with localized disease (P = 0.005). Tamoxifen treatment was significantly associated with higher circulating and platelet-derived VEGF levels. Circulating VEGF did not correlate with any clinicopathological factor, including MVD or VEGF expression. VEGF expression was significantly correlated with estrogen receptor status and inversely correlated with tumor grade. MVD correlated with tumor size. Tamoxifen-induced increases in VEGF may be important in clinical prognosis or associated pathologies.
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PMID:Vascular endothelial growth factor (VEGF) in breast cancer: comparison of plasma, serum, and tissue VEGF and microvessel density and effects of tamoxifen. 1085 Apr 35

Tamoxifen (TAM) is known to be associated with several types of endometrial pathologies, e.g. hyperplasias, polyps and endometrial carcinomas, sometimes of special histologic type. Here we report a rare case of endometrial metastasis from a breast carcinoma (ductal carcinoma) discovered during TAM therapy. This occurrence does not suggest that TAM treatment causes endometrial metastases of breast cancer. However, clinicians should be aware of this possibility and provide patients receiving TAM therapy with close gynecologic follow-up using liberal indications for endometrial biopsies.
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PMID:Endometrial metastasis from breast cancer in a patient receiving tamoxifen therapy. 1096

Of the 25,000 new cases of breast cancer annually in the UK, at least half will develop metastases at some time. Approximately one-third of these will be hormone-sensitive and thus suitable for endocrine manipulation. Such patients may live for several years. Care should be patient-centred and evidence-based, with primary care playing an integral part in the multidisciplinary team. Quality of life is paramount, and largely determines decisions to change endocrine therapy. Tamoxifen remains the first choice treatment, but newer agents, in particular the oral aromatase inhibitors, have successfully extended the range of therapy available. Ovarian ablation can be effectively achieved using LHRH analogues, which have the advantage of being reversible if ineffective. In future, further improvements in outcome are likely with new pure antioestrogens and the possibility of sequential or combined use of existing drugs.
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PMID:Management of advanced breast cancer with endocrine therapy: the role of the primary healthcare team. 1122 Dec 80

Hormone therapy of breast cancer has been dominated for a very long time by a single class of drugs, the antiestrogens, and especially tamoxifen. Tamoxifen has been the standard treatment in the adjuvant, neoadjuvant, and metastatic contexts. Ten years ago a new generation of aromatase inhibitors became available that was more selective than previous generations. They form two groups that are quite distinct from a pharmacological standpoint: type II non-steroid inhibitors and type I steroid inhibitors or rather steroid "aromatase inactivators". Aromatase inhibitors are prescribed to menopausal women. They are active in patients with tamoxifen-resistant metastatic cancer. They are a potential alternative to tamoxifen in first-line therapy of women with metastatic cancer. They have been proven useful as neoadjuvant therapy. They are under study in several trials in an adjuvant context. Many issues still remain outstanding.
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PMID:[Aromatase inhibitors: therapeutic outlook]. 1125 Jun 7

The value of adjuvant endocrine therapy in saving lives of women with estrogen receptor-positive (ER(+)) early-stage breast cancer cannot be disputed. Tamoxifen has proven to be effective in improving relapse-free and overall survival in both pre- and postmenopausal women with ER(+) early-stage breast cancer. In the meta-analysis of the Early Breast Cancer Trialists' Collaborative Group, the proportional reduction in recurrence and mortality for 5 years of tamoxifen therapy was 50% and 28% respectively for patients with ER(+) tumors. These reductions in recurrence and mortality were similar in both lymph node-negative (N(-)) and lymph node-positive (N(+)) patients and translate to an absolute improvement in 10-year survival of approximately 11% in N(+) patients and 6% in N(-) patients. Current data suggest that about 5 years of tamoxifen therapy is the optimal duration of treatment. For women with ER(-)/progesterone receptor-negative (PR(-)) tumors, tamoxifen does not lower the risk of distant metastases or improve survival. In ER(+) patients, the addition of tamoxifen to chemotherapy further lowers the risk of recurrence by about 30% to 40% when compared to chemotherapy alone. In premenopausal women with ER(+) breast cancer, ovarian ablation has proven to be as effective as chemotherapy in improving both relapse-free and overall survival and the potential additive role of ovarian ablation to chemotherapy and/or tamoxifen is presently being explored in clinical trials. The combination of tamoxifen and ovarian ablation is currently being tested and may be superior to tamoxifen alone. In addition, newer, more effective, and less toxic aromatase inhibitors are also being evaluated in clinical trials in the adjuvant setting and have great promise. "Pure" antiestrogens or selective estrogen receptor down-regulators (SERDs) will be studied in adjuvant clinical trials in the near future. Recent data also suggest that molecular markers such as HER-2/neu may predict the response to endocrine therapy, and other predictive factors are currently being evaluated. Lastly, there is renewed interest in neoadjuvant endocrine therapy, a treatment option that may select those patients with early-stage breast cancer most likely to benefit from endocrine therapy.
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PMID:Role of adjuvant endocrine therapy in early-stage breast cancer. 1149 25

Endometrial cancer is usually diagnosed at an early stage where surgery alone is the adequate therapy. Chemotherapy and hormonal treatment are therefore almost exclusively performed in palliative situations. Hormonal treatment with progestogens (medroxyprogesterone acetate and megestrol acetate) should be the therapy of choice primarily as these drugs are very well tolerated. Tamoxifen and GnRH analogs are further options but are seldom used. The response rates to hormonal treatment are relatively low (max. 25 %) with short remissions in most cases. - So far neither hormonal treatment nor cytotoxic chemotherapy has been shown to have substantial benefits in the adjuvant setting. In some selected high risk cases (serous papillary carcinomas, extra uterine manifestation) adjuvant chemotherapy may be an option following surgery, before or after radiotherapy. Age, general condition and morbidity of the patients need to be considered as limiting factors for chemotherapy. Crucial for the prognosis of all endometrial cancer patients however, is the stage adapted surgery. - Cytotoxic chemotherapy has failed to bring a break through in the therapy of advanced endometrial cancer. Cisplatin plus doxorubicin is the standard combination to date, with anthracyclines being the more important component. In a mono-therapy setting, doxorubicin and epirubicin are well tolerated and convenient in their efficacy. For recurrent and metastatic disease, docetaxel is being evaluated for efficacy and side effects in a multicenter phase II trial.
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PMID:[Hormonal therapy and chemotherapy of endometrial cancer]. 1187 14

Malignant transformation of eccrine spiradenoma is extremely rare. We describe the case of a 70-year-old man with malignant eccrine spiradenoma of the forearm and metastases to the axillary lymph nodes. Surgical excision with adequate margins and lymph node dissection was performed. Tamoxifen therapy was instituted after obtaining positive immunostaining results for estrogen receptor. After 41 months of follow-up, there has been no recurrence or distant metastases. Wide local excision and close follow-up are crucial in the management of malignant eccrine spiradenoma. The role of other therapeutic modalities, including hormonal therapy, remains to be determined.
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PMID:Malignant eccrine spiradenoma. 1195 66

The medical management of invasive breast cancer has evolved based on the recognition that surgery alone was associated with few long-term cures. This Update will review the current status of breast cancer medical management in three areas: prevention in individuals with an elevated risk, adjuvant (postoperative) treatment of early breast cancer, and treatment principles in metastatic disease. Tamoxifen has emerged as a promising agent in the treatment of women at an increased risk for breast cancer and in those with in situ disease. However, the risks of treatment must be carefully weighed against the benefits in these cohorts of women with an excellent overall prognosis. This same principle can be applied to the use of adjuvant treatment in early invasive breast cancer, where the goal is cure. Adjuvant polychemotherapy is recommended in women considered at high-risk for relapse and death. In addition, women with hormone-sensitive breast cancer are offered adjuvant taxmoxifen. Nonetheless, there are some patients with low-risk disease or those with significant co-morbidities that are unlikely to benefit from adjuvant therapies and likely to sustain toxicities. The treatment goal in metastatic breast cancer is focused on palliation of symptoms as fewer than 10% of such patients achieve 5-year survival. However, novel targeted therapies are changing the treatment armamentarium and hold great promise. These new directions of treatment will be discussed as well as areas of controversy.
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PMID:Medical management of breast cancer: today and tomorrow. 1203 Jan 8


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