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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacology of the antiestrogen tamoxifen is reviewed. The drug is currently used extensively in the treatment of all stages of breast cancer and is being considered as a preventive agent for women at high risk for breast cancer. Extensive laboratory studies demonstrate that tamoxifen is a tumoristatic agent in models of mammary carcinogenesis. Any clinical applications must therefore consider long-term (5-10 years) treatment strategies. Tamoxifen prevents rat mammary carcinogenesis. However, the timing of the carcinogenic insult is unknown among women. Tamoxifen must be considered to be a chemosuppressive agent to prevent the appearance of the primary tumor rather than to prevent the initial carcinogenic insult.
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PMID:Chemosuppression of breast cancer with long-term tamoxifen therapy. 200 27

The authors analyze estrogen receptors in 501 cases of breast cancer and the therapeutic response achieved with treatment of patients who relapsed. The method utilized to determine the presence of estrogen receptor was cytosol protein-counting and Dextran coated charcoal (DCC) saturation analysis. Patients were treated with chemotherapy when the primary tumor was estrogen-receptor negative. If receptor was present, anti-estrogen drug (Tamoxifen) was added. Patients previously treated with the anti-estrogen presented a better response to anti-estrogen therapy and a lower recurrence rate. Recurrences were more frequent in estrogen receptor negative cases and better responses to treatment were found in estrogen receptor positive ones.
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PMID:Estrogen receptors in breast cancer--therapeutic response to the treatment of recurrences. 288 37

The paper presents interim results of an on-going randomized trial of adjuvant tamoxifen (40 mg daily for 2 years) versus no endocrine adjuvant therapy in postmenopausal women with early breast cancer. A total of 1407 patients were included in the study between November 1976 through June 1984. Estrogen receptor (ER) data were available on 1184 patients (84%). The median follow-up was 53 months. Adjuvant tamoxifen increased the recurrence-free interval (P less than 0.01) but had no significant effect on overall survival. Treatment failures were reduced by 25% (P less than 0.01) and deaths by 7% (P greater than 0.05). Tamoxifen mainly decreased the frequency of loco-regional recurrence whereas distant metastases were less affected. The treatment effect was independent of tumor stage but was significantly related to the estrogen receptor (ER) content of the primary tumor. Tamoxifen appeared ineffective among ER negative patients, and the greatest effect was seen among those with high levels of ER. The results indicate that the main mechanism of action of adjuvant tamoxifen is similar to that suggested in advanced disease, i.e. an interaction with the estrogen receptor.
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PMID:The Stockholm trial on adjuvant tamoxifen in early breast cancer. Correlation between estrogen receptor level and treatment effect. 332 86

Forty-six evaluable postmenopausal patients with locally advanced, inoperable T3-T4 breast carcinoma were treated with tamoxifen 10-20 mg twice daily for a period at least 6 weeks. Eight patients (17%) had an objective response at the primary tumor site after 6 weeks of treatment. Improvement of response with a further single tamoxifen therapy was observed in 7 patients, resulting in an overall objective response in 14 of 46 (30%). Median duration of response was 8 months (range 2-24). No response was obtained in the 5 patients with inflammatory signs. Toxicity of treatment was minimal. Medial survival was 10 months (responders 17.5, non-responders 9). Tamoxifen seems to be safe and effective treatment for locally advanced breast cancer without inflammatory signs in postmenopausal women.
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PMID:Tamoxifen therapy in postmenopausal advanced breast cancer: efficacy at the primary tumor site in 46 evaluable patients. 728 Dec 42

Phase III randomized clinical trials have greatly contributed to our understanding of the pathobiology of neoplastic disease and, particularly, to therapeutic progress. However, randomized Phase III studies are no better than or are critically dependent on Phase I and Phase II studies for positive therapeutic leads that are compelling enough to test in the Phase III arena. The variables involved in the series of randomized trials that led to the curative treatment of acute lymphocytic leukemia also resulted in an understanding of the principles of cancer therapy in therapeutic research. These principles, when applied to Hodgkin's disease in non-Hodgkin's lymphoma, testis cancer, childhood solid tumors, and others, resulted in a substantial cure rate for those diseases. However, for the adult epithelial common solid tumors, a second strategy, adjuvant chemotherapy, was required This has resulted in a 20% reduction in mortality in patients with node positive and node negative breast cancer. Tamoxifen has been similarly effective in patients with postmenopausal breast cancer. In colon cancer, adjuvant chemotherapy with fluorouracil plus levamisole has decreased mortality to a comparable degree. New agents, modulations, combination chemotherapy, and biotherapeutics are being addressed to the adjuvant situation which has proven effective in a variety of neoplastic diseases. A third strategy is neoadjuvant chemotherapy. This involves the use of chemotherapy first for patients with solid tumors, designed to down-stage the primary tumor thus making it more susceptible to less radical surgery and to organ- or limb-sparing procedures in osteogenetic sarcoma and in head and neck cancer. For example, neoadjuvant chemotherapy has not resulted in an increased survival as compared with the appropriate control but has allowed for important quality-of-life contributions, such as limb-sparing and radical surgery-sparing procedures. In addition to new agents and combination chemotherapy, dose is a critical variable. This is most evident clinically in the transplantation arena. Comparative studies recently completed, for example, in patients with adjuvant breast cancer and with acute leukemia indicate that dose is a significant factor in tumor control.
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PMID:Randomized clinical trials and other approaches in clinical research. 795 73

We present a case of endometrial carcinoma accompanied with mucinous cystadenoma in a 70-year-old postmenopausal woman treated with tamoxifen for breast cancer demonstrated by MR imaging. Tamoxifen therapy (20 mg/day) had been carried out for more than 11 years since the surgical procedure for the primary tumor. MR images showed a markedly enlarged uterus containing endometrial carcinoma, cystic atrophy of the endometrium, and a right adnexal mass with multicystic components of various signal intensities.
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PMID:MR appearance of endometrial carcinoma and mucinous cystadenoma in a postmenopausal patient treated with tamoxifen for breast cancer. 981 31

Tamoxifen is a nonsteroidal antiestrogen that has become the frontline endocrine therapy for all stages of breast cancer. The drug is the only single-agent therapy that, when used in an adjuvant fashion, produces a survival advantage in postmenopausal women. Survival is longer when the estrogen receptor content of the primary tumor is higher, although receptor-poor patients still have a survival advantage from adjuvant tamoxifen equivalent to that noted with combination chemotherapy. The added advantages of tamoxifen are a maintenance of bone density and a decrease in fatal myocardial infarction. Although side effects from tamoxifen are few, patients must be examined for preexisting endometrial carcinoma before beginning drug use. Tamoxifen does not prevent the growth of endometrial tumors. Spotting and vaginal bleeding in postmenopausal patients taking tamoxifen should be followed up with a thorough gynecological examination. The incidence rate of endometrial cancer for tamoxifen-treated patients is 2 per 1000 patients per year. More than 80% of detected endometrial tumors are stage 1 disease and can be cured by hysterectomy.
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PMID:Long-term Tamoxifen Therapy for the Treatment of Breast Cancer. 1088 88

Tamoxifen is one of the most effective treatments for breast cancer. Standard practice is to select patients who are likely to respond to this therapy through the evaluation of estrogen receptor (ER) and progesterone receptor (PR) in the primary tumor tissue. Over the past 25 yr that physicians have been using ER determination to guide tamoxifen use, numerous studies have demonstrated that this molecular marker is useful in predicting benefit from tamoxifen. ER has been analyzed for many years using ligand-binding assays. However, current practice involves the use of immunohistochemical-based assays to detect ERalpha Immunohistochemistry (IHC) has several advantages. For example, IHC evaluates tumor cell heterogeneity, can be used to study small samples, is less expensive, and allows direct correlation with multiple histopathological tumor features and other molecular markers. PR, an estrogen-responsive protein, can also be useful in predicting response to tamoxifen in specific clinical situations. In recent years, several other markers of tamoxifen response have been examined, including: pS2 (another estrogen-regulated protein), heat-shock proteins 27 and 70, bcl-2 protein, c-erbB-2 (HER-2/neu) oncoprotein, and mutated p53 tumor suppressor protein. In this article, we present an analysis of the data on these new molecular markers. Overall, from numerous studies, the data indicate that in addition to ERalpha bcl-2 is a potential candidate to help further improve our ability to predict response to tamoxifen. ER and bcl-2 are the most useful molecular markers to better identify breast cancer patients who will respond to tamoxifen and who will have prolonged survival.
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PMID:Molecular markers for predicting response to tamoxifen in breast cancer patients. 1105 Oct 41

Overexpression and altered function of EphA2 receptor tyrosine kinase are critical in the progression of breast cancer and provide a target for breast cancer therapy. We have previously demonstrated that EphA2 overexpression decreases estrogen dependence and Tamoxifen sensitivity both in vitro and in vivo. EA5, a novel monoclonal antibody that mimicks the binding of ephrin A to EphA2, reverses the effect of EphA2 overexpression and restores Tamoxifen sensitivity in EphA2-transfected MCF-7 cells in vitro. To explore the role of EphA2 overexpression on ER-dependent mechanisms, we used two different ER+/EphA2-transfected cell line models (MCF-7(neo)/MCF-7(EphA2) and T47D(neo)/T47D(EphA2)). EA5 inhibits primary tumor growth and restores Tamoxifen sensitivity in the MCF-7(EphA2) xenografts. Using the T47D(EphA2) in vitro model, we verified that EphA2 decreases ER activation in response to E2 stimulation consistent with our earlier results in MCF-7(EphA2) model. We found no direct interaction between ER and EphA2 and no difference in expression of canonical ER-dependent proteins or ER co-regulators. However, E2 stimulation phosphorylates FAK(Tyr925) only in ER+/EphA2+ cell lines. Treatment of T47D(EphA2) cells with EA5 and Tamoxifen leads to dephosphorylation of FAK(Tyr925) in response to E2. Our data demonstrate that dual targeting of EphA2 and ER is a promising approach for delaying resistance to Tamoxifen. The data support our hypothesis that EphA2 impacts ER function via a FAK dependent pathway.
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PMID:Dual targeting of EphA2 and ER restores tamoxifen sensitivity in ER/EphA2-positive breast cancer. 2060 65

The patient was a 68-year-old woman who had a right mastectomy performed in another hospital in 1987. Her right breast tumor was histologically diagnosed IDC and ER(-), with an uncertain PgR and HER2. Tamoxifen was administered as adjuvant therapy for five years after surgery. Because she had abdominal pain in January, 2007, she consulted her family doctor. At that doctor's hospital, metastatic tumors of the liver were found, and she was therefore referred to our hospital. A liver biopsy of the tumor was conducted in our hospital, and hormone therapy was also conducted because her cancer status was ER(+), PgR(+), HER2(0), and was not life-threatening. Hormone therapy had a good effect on the tumor. ER, PgR and HER2 expression might make the difference between a primary tumor and a metastatic one, as in this case. Therefore, we should perform biopsies on metastatic tumors to determine the best treatment method. There is a possibility that hormone therapy will become an effective therapeutic procedure for breast cancer patients who are hormone receptor positive, are not in a life threatening situation, and have had a long, disease-free survival. We reported one case in which the aromatase third generation inhibitor letrozole was effective for treating liver metastases of breast cancer.
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PMID:[A case of liver metastasis of breast cancer responding to letrozole]. 2233 38


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