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

A number of recent studies have suggested that survival among premenopausal women after primary treatment of breast cancer may be affected by the estimated hormonal milieu at the time of surgery, especially in those with axillary lymph node metastases. The concept has created considerable controversy and has resulted in the publication of many negative reports. However, several biological mechanisms have been suggested for the observed survival advantage. These include cyclical patterns of immune function, as well as cell division and cell death, that correlate with hormonal fluctuations of the menstrual cycle. Comparisons among studies of timing have been complicated by differences in menstrual cycle divisions, variability in the sources of study populations, limited availability of menstrual history data, and changes over the past 2 decades in primary and adjuvant breast cancer therapy. Several recent publications have been enhanced by the availability of serum collected at the time of surgery that enables accurate measurement of the hormonal milieu. In these studies, the likelihood of misclassification by menstrual cycle phase is reduced, and dependence on recalled menstrual history is eliminated. High progesterone levels have been associated with improved survival. These findings have encouraged some to suggest that perioperative administration of progesterone or tamoxifen (Nolvadex) may provide a preventive avenue comparable to scheduling surgery during the luteal phase. Further multidisciplinary studies are needed, however, to clarify the influence of the naturally occurring or medically induced hormonal milieu at the time of breast cancer surgery on survival in premenopausal women.
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PMID:The timing of breast cancer surgery during the menstrual cycle. 934 56

The choice of endocrine agent for breast cancer depends on the menopausal status of the patient, the stage of disease, prognostic factors, and the toxicity profile of the agent. Endocrine therapies are typically given sequentially, with the least toxic therapy given first. Tamoxifen is considered first-line endocrine therapy for all stages of breast cancer. New antiestrogens in development include nonsteroidal agents related to tamoxifen and pure steroidal antiestrogens. Luteinizing hormone-releasing hormone agonists are an effective form of endocrine therapy for premenopausal women with advanced breast cancer, and aromatase inhibitors are effective in postmenopausal women. Newer and more selective aromatase inhibitors that are p.o. active and have improved side-effect profiles have been developed. Recent trials have found these agents to improve survival in comparison to the progestins; thus, aromatase inhibitors are replacing progestins as second-line therapy for metastatic disease. Current trials are examining the potential role of aromatase inhibitors as first-line therapy for metastatic disease or as adjuvant therapy for early disease. The antiprogestins and antiandrogens studied thus far have had only limited success in breast cancer clinical trials.
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PMID:Update on endocrine therapy for breast cancer. 953 18

Liver metastases account for over 70% of deaths resulting from colorectal carcinoma, with survival rates varying between 6-18 months. At present, surgical resection offers the only hope for a cure, while chemotherapy, focal destructive techniques and selective internal radiation offer palliative care. Tamoxifen, a non-steroidal anti-oestrogen is primarily known for treating oestrogen receptor (ER)-positive breast cancer. Some studies suggest that tamoxifen may have beneficial effects in malignancies other than breast cancer. These inhibitory effects, which have been shown to be independent of the ER, highlight new mechanisms of therapeutic action. Using an intrasplenic animal model we report the efficacy of tamoxifen on experimental liver metastases. In this model, a dimethyl hydrazine-induced colon carcinoma cell suspension is introduced into the portal circulation via the spleen, which results in secondary tumour deposits in the liver in virtually all animals. Tamoxifen was administered at a dose of 1 mg/kg suspended in 1.0% methyl cellulose. The control group received an equal volume of the vehicle. The reagents were administered s.c. on the day of metastases induction and were continued daily over a 4 week period. The effect of tamoxifen on tumour growth was assessed by stereology and bromodeoxyuridine immunohistochemistry at selected time points. Data were assessed by a multiple analysis of variance where P < 0.05 was considered significant. In the control group the volume of metastases increased from 44 +/- 41 mm3 at day 10 to 517 +/- 380 mm3, 1394 +/- 598 mm3 and 2082 +/- 675 mm3 by days 16, 22 and 28, respectively. Daily administration of tamoxifen exerted an inhibitory effect on tumour growth during the first 3 weeks, recording a volume of 421 +/- 299 mm3 by day 22 compared with the control group at that time point (P = 0.00004). The inhibitory effect diminished by the fourth week recording a tumour volume of 1344 +/- 674 mm3 by day 28. Inhibition of tumour growth at day 22 coincides with a reduction of cells in the S phase of the cell cycle. The percentage of brdU-positive nuclear profiles in metastases of tamoxifen-treated mice at 3 weeks was 35.87 +/- 5.60% compared with 48.01 +/- 3.96% in the control group (P = 0.001). These data suggest that tamoxifen has a potent inhibitory action on colorectal liver metastases by exerting an effect on cell proliferation.
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PMID:Tamoxifen inhibits colorectal cancer metastases in the liver: a study in a murine model. 964 52

Only a few cases on mucinous adenocarcinomas of the vulva have been reported. In this study, we present a case of a 75-year-old woman with a tumor in the left major labium. Because biopsy had shown formations of squamous cell carcinoma, radical vulvectomy with bilateral inguinal and femoral lymph node dissection were performed. At that time, histology was interpreted as small-cell, anaplastic carcinoma, with focal epidermoid differentiation. Postoperative radiation therapy was performed. Sixteen months after surgery, the patient presented with bilateral breast carcinomas. Histology showed a scirrhous carcinoma of the left and a medullary carcinoma of the right breast, but no lymph node metastases. Histochemical and immunohistochemical re-examination of the vulvar carcinoma now revealed a mucinous adenocarcinoma with neuroendocrine differentiation. The tumor expressed neuroendocrine markers such as chromogranin A and protein gene-product (PGP) 9.5, as well as peptides of the vasoactive intestinal polypeptide (VIP) family, and serotonin. Histochemical silver stains demonstrated Grimelius argyrophilia and Masson argentaffinity. Because of positive estrogen and progesterone receptor status of both breast cancers, postoperative Tamoxifen therapy was performed. The patient is still alive four years after vulvectomy.
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PMID:Primary neuroendocrine differentiated mucinous adenocarcinoma of the vulva: case report and review of the literature. 967 64

Extensive clinical experience, summarised in the recent overview of the Early Breast Cancer Trialists' Collaborative Group (EBCTCG), have confirmed that tamoxifen reduces the rate of both disease recurrence and mortality when administered as adjuvant therapy in women with early breast cancer. Tamoxifen is now established as the preferred adjuvant agent in postmenopausal women; in particular, patients with node-positive, estrogen receptor-positive breast cancer have the most to gain from tamoxifen therapy. Data from a decision-analysis model indicated that tamoxifen monotherapy had a cost-utility ration {$US6000 per additional quality-adjusted life-year (QALY), in 1989 dollars} 5 to 6 times lower than that cited as the cost-acceptability cut-off point in the US. While tamoxifen monotherapy is effective in postmenopausal women, the EBCTCG overview findings indicate that a combined regimen of tamoxifen and antineoplastic chemotherapy has superior efficacy in the same patient group. An issue of current interest is whether the added benefit offered by such a regimen can be justified in terms of added toxicity and cost. Data from a decision-analysis model indicate that combined therapy has a high incremental cost-utility ratio ($US58 000 per additional QALY, in 1989 dollars) compared with no therapy in postmenopausal women. However, the quality-of-life measures TWiST (Time Without Symptoms and Toxicity) and Q-TWiST (quality-adjusted TWiST) indicate that the early toxicity associated with a combined regimen appears to be justified given the superior long term benefits. Patient preference data from 1 study further indicate that the degree of benefit offered by a combined regimen would be acceptable to the majority (73%) of patients. Other areas where pharmacoeconomic analyses may help define more closely the optimal use of adjuvant tamoxifen is in patients at low risk of developing metastatic disease and in determining the optimal duration of therapy. Both areas require further clinical data. In conclusion, tamoxifen adjuvant monotherapy has a low cost-utility ratio in postmenopausal women with node-positive, estrogen receptor-positive breast cancer. Combined therapy in the same patient group has a high cost-utility ratio compared with no therapy but quality-of-life and patient preference data suggest that the costs may be justified. Firm conclusions relating to the use of the drug in other patient subgroups and the optimal duration of therapy await further research.
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PMID:Tamoxifen: a review of pharmacoeconomic and quality-of-life considerations for its use as adjuvant therapy in women with breast cancer. 1014 67

Recent trials comparing single-agent vs combination therapy in metastatic breast cancer suggest that it may be time to reconsider the belief that combination chemotherapy is the gold standard of treatment. Based on the limited randomized trial data available to date, high-dose chemotherapy with stem-cell rescue should not be viewed as "state-of-the art" treatment for metastatic disease and should be used only in the context of clinical trials. Recent trials have explored the optimal dosing and scheduling of the taxanes, as well as the possible role of these agents in combination regimens. Capecitabine (Xeloda), a new oral fluoropyrimidine, appears to be comparable in efficacy to CMF (cyclophosphamide, methotrexate, and fluorouracil), and preclinical data suggest possible synergy between this agent and the taxanes. Other promising agents under study include liposome-encapsulated doxorubicin (TLCD-99), an immunoconjugate linking a chimeric human/mouse monoclonal antibody to doxorubicin molecules; MTA (LY231514), a multitargeted antifolate; and marimistat, a broad-spectrum matrix metalloproteinase inhibitor. Tamoxifen (Nolvadex) remains the most important hormonal agent, but new antiestrogens and selective estrogen receptor modulators (SERMs) may provide alternatives. The potential role of new aromatase inhibitors as first-line hormonal agents requires further study. Finally, the possible synergy between trastuzumab (Herceptin), a recombinant humanized monoclonal antibody to the HER-2/neu protein, and paclitaxel (Taxol) is being studied in two clinical trials.
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PMID:Update on the management of advanced breast cancer. 1035 85

Breast cancer cells can metastasize early in the development of primary tumors. Adjuvant chemotherapy improves disease-free survival and overall survival (OS) in patients with early-stage breast cancer, both in premenopausal and postmenopausal women. Tamoxifen improves OS in patients whose tumors are estrogen-receptor-positive, regardless of age. Although the relative risk reduction with these interventions is the same for all patients, the absolute benefit is more prominent in patients at the highest risk of relapse. All patients with involved lymph nodes should receive adjuvant chemotherapy if no contraindications occur. In patients with negative lymph nodes, adjuvant chemotherapy is recommended if the invasive tumor is moderately or poorly differentiated, the tumor size is larger than 1 or 2 cm, or hormone receptors are negative. Other prognostic and predictive indicators of response to chemotherapy and hormonal therapy remain investigational. Models that combine several factors to determine a patient's risk of relapse and death are presented. Neoadjuvant chemotherapy in conjunction with radiation therapy and surgery is the treatment of choice for patients with locally advanced breast cancer. Recently, this approach has been extended to patients with small, operable tumors. Neoadjuvant chemotherapy can downstage tumors effectively, leading to improved cosmetic results and possibly to a reduction in local recurrence rate. Another advantage of neoadjuvant therapy is the in vivo assessment of tumor sensitivity to chemotherapy, which allows optimization of available therapeutic agents. One disadvantage of neoadjuvant chemotherapy is that preoperative treatment causes an alteration of information regarding lymph node status prior to systemic treatment. Although the optimal chemotherapy regimen has not been established, doxorubicin-containing regimens are considered superior to non-doxorubicin-containing regimens. The role of high-dose chemotherapy is not well defined in the adjuvant setting and remains investigational. The taxanes paclitaxel and docetaxel are moving rapidly from the metastatic setting to the adjuvant setting. A better understanding of the biology of breast cancer is providing molecular tools to study novel treatment approaches. Oncogenes and tumor suppressor genes are emerging as important indicators of response to chemotherapy. These molecules, in turn, become targets for therapy. Novel agents under development are presented.
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PMID:Integration of Systemic Chemotherapy in the Management of Primary Breast Cancer. 1038 20

Two cases of metastatic breast cancer are reported in which endocrine chemotherapy with Toremifene + 5'-DFUR proved markedly effective. Case 1: A 69-year-old female. After CAF therapy as a adjuvant chemotherapy, Tamoxifen and Tegafur had been administered. At the 5th postoperative year, multiple metastases to lung and a rise in the tumor marker were found. Since the patient was not desirous of intensive chemotherapy, administration of Toremifene 120 mg/day and 5'-DFUR 800 mg/day was initiated. The patient showed PR 9 months after and achieved CR 14 months later. Case 2: A 48-year-old female. CAF therapy for a total of 6 cycles was performed as adjuvant chemotherapy. The patient was administered Tamoxifen and followed. On bone scintigrams 3.5 years after surgery, an abnormal accumulation appeared in the left sternoclavicular joint, and an infiltrative tumor mass was formed in the skin of that region. Administration of Toremifene + 5'-DFUR was initiated. After 6 months, the infiltrative mass disappeared. These findings are suggestive of the effectiveness of this combined chemotherapy.
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PMID:[Endocrine chemotherapy (high-dose toremifene + 5'-DFUR) found markedly effective for 2 cases of metastatic breast cancer]. 1039 29

Hepatocellular carcinoma (HCC) is a common, potentially lethal tumor in human patients. Because the serum levels of transforming growth factor-beta1 (TGF-beta1) correlate with outcome in patients with HCC and because TGFbeta1 mRNA expression is increased in HCC tissues, it raises the possibility that TGF-beta1 may be of importance in the development, growth, and metastases of HCC. Tamoxifen has been used for the treatment of human HCC. However, clinical trials have produced conflicting results. To further delineate whether tamoxifen may be of benefit in altering the course of HCC, we documented the effects of 4-hydroxytamoxifen and 17beta-estradiol on TGF-beta1 mRNA and protein levels and cell proliferation in a human HCC cell line. PLC/PRF/5 cells were treated with carrier (controls), 4-hydroxytamoxifen, 17beta-estradiol, or TGF-beta1. 4-Hydroxytamoxifen and 17beta-estradiol decreased TGF-beta1 mRNA and protein levels in a time- and dose-dependent manner. TGF-beta1 significantly inhibited PLC/PRF/5 cell proliferation, whereas both 4-hydroxytamoxifen and 17beta-estradiol stimulated PLC/PRF/5 cell proliferation. The stimulatory effects of 4-hydroxytamoxifen on PLC/PRF/5 cell proliferation raise concerns regarding its use in the treatment of HCC in human patients and suggest that 4-hydroxytamoxifen may have no beneficial effects in some patients with HCC.
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PMID:Regulation of transforming growth factor-beta1 gene expression and cell proliferation in human hepatocellular carcinoma cells (PLC/PRF/5) by tamoxifen. 1040 64

Fibroepithelial stromal polyps of the vulvovaginal region are benign lesions that, when bland or hypocellular, are readily recognized. However those that exhibit bizarre cytomorphology, atypical mitoses, or hypercellularity, raising the possibility of malignancy, continue to be underrecognized. The authors reviewed a series of fibroepithelial stromal polyps to characterize further the morphologic features that can lead to a misdiagnosis of sarcoma. A total of 33 of 65 consecutive cases of fibroepithelial stromal polyps retrieved from the authors' consultation files were remarkable for marked hypercellularity (33 of 33), marked cytologic pleomorphism (21 of 33), mitotic counts of more than 10 mitoses per 10 high-power fields (12 of 33), and the presence of atypical mitoses (14 of 33). A total of 16 of 33 lesions had three or more of these features. Important morphologic clues to the diagnosis (shared with usual polyps at this site) were lack of an identifiable lesional margin, extension of abnormal stromal tissue up to the mucosal-submucosal interface, and the frequent presence of individually scattered multinucleate stromal cells, most often located close to the surface epithelium. Immunohistochemically, seven of 12 cases were desmin positive and one of 11 cases were smooth muscle actin positive. The age range of patients was 16 to 75 years (median, 32 years), and 21 patients (64%) were premenopausal. Sites included the vagina (18 of 33), cervix (seven of 33), and vulva (eight of 33). A total of 14 of 33 patients were pregnant, three patients were taking Tamoxifen, and one patient was on oral progesterone. Eight of 33 patients had multiple lesions at the time of presentation, of whom five were pregnant. Clinical follow-up was available in 21 of 33 patients. Three of 21 patients with follow-up had local, nondestructive recurrence. Two of these patients had multiple recurrences. None of the patients followed developed metastases. Cytologic atypia has been a previously recognized feature in these lesions; however, the occurrence of marked stromal cellularity and a mitotic rate of more than 10 mitoses per 10 high-power fields have not been emphasized previously. Moreover, the combination of these features has only rarely been documented. Awareness of the spectrum of histologic features that these lesions can exhibit is crucial in their accurate recognition, thus avoiding potential overtreatment.
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PMID:Cellular pseudosarcomatous fibroepithelial stromal polyps of the lower female genital tract: an underrecognized lesion often misdiagnosed as sarcoma. 1068 Aug 91


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