Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two hundred and fifty evaluable patients with breast cancer entered a protocol combining neoadjuvant and consolidation therapy by vinblastine (V), thiotepa (T), methotrexate (m) and 5-fluorouracil (f) (VTMF) with or without Adriamycin (A) (Doxorubicin; Adria Laboratories, Colombus, OH USA), and radiation therapy as exclusive locoregional treatment. Tamoxifen was given to 195 patients, 130 post menopausal and 65 pre-menopausal, and was omitted in 55 patients (31 postmenopausal and 24 pre-menopausal). There were 19 stage I, 86 IIa, 51 IIB, 36 IIIA and 58 IIIB. Primary chemotherapy induced tumor volume regression of more than 75% in 41% of the patients and complete clinical regression in 30% of the patients. The 5 years DFS rates were 100% for stage I, 82% for stage IIA, 61% for stage IIB, 46% for stage IIIA and 52% for stage IIIB patients. Among the 72 primary relapses there were 39 distant metastases, 6 locoregional and distant metastasis and 27 isolated locoregional metastases. The actuarial rate of locoregional recurrence is 13% for T2, 18% for T3, 19% for T4. At 5 years the rate of breast preservation was 94%. Cosmetic results are excellent or good for most patients. The 5 years overall survival (OS) were 95% for stage I, 94% for stage IA, 80% for stage IIB, 60% for stage IIIA and 58% for stage IIIB. In multivariate analysis tumor regression appears as an independent and significant factor. This parameter should be preserved in many patients with infiltrative breast cancer.
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PMID:[Tumor regression as a prognostic factor in breast cancer]. 187 5

A procedure for the extraction of tamoxifen and metabolites from various rat and human tissues was developed and verified. With this method, we determined the drug and metabolite concentrations during one dosing interval in various tissues (brain, fat, liver, heart, lung, kidney, uterus, and testes) of rats given tamoxifen once daily for 3 or 14 days, and in various normal and malignant tissues obtained during surgery or at autopsy from patients with breast cancer treated with tamoxifen. In the rat, the concentrations of tamoxifen and metabolites in most tissues were 8- to 70-fold higher than in serum. The highest levels were observed in lung and liver; substantial amounts were also recovered from kidney and fat. Fluctuations of metabolites and tamoxifen content in most tissues were observed during one dosing interval, corresponding to a ratio of 4:8 between Cmax and Cmin, except in fat and testicular tissues, where the drug concentrations were relatively stable. In addition to tamoxifen, N-desmethyltamoxifen, followed by 4-hydroxytamoxifen, 4-hydroxy-N-desmethyltamoxifen, and N-desdimethyltamoxifen, were abundant in most tissues. In contrast, adipose tissue contained only small amounts of these metabolites. The concentrations of tamoxifen and metabolites found in human normal and malignant tissues confirmed and extended the conclusions made in the experiments with rats. In humans, levels were 10- to 60-fold higher in tissues than in serum, and relatively high concentrations were detected in liver and lung. Additionally, pancreas, pancreatic tumor, and brain metastases from breast cancer and primary breast cancer retained large amounts of drug. Again, the amounts of demethylated and hydroxylated metabolites were high in most tissues, except in fat. Tamoxifen and some metabolites were also present in specimens of skin and bone tissue. In one patient, significant amounts of drugs could be detected in lung, heart, ovary, and intestinal wall 14 months after withdrawal of tamoxifen, demonstrating efficient retention and slow washout of these compounds in human tissue.
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PMID:Distribution of tamoxifen and its metabolites in rat and human tissues during steady-state treatment. 189 76

Tamoxifen (TAM), a nonsteroidal antiestrogen, is used for pre- and postmenopausal patients with breast cancer. Recent reports suggest that TAM may cause endometrial neoplasia. This study is designed to evaluate the oncogenic potential of low-dose TAM on the endometrium. Initially, endometrial screening of patients with breast cancer who had received TAM therapy for at least 12 months was conducted. Seventy patients were interviewed and office endometrial biopsies were obtained from thirty-eight patients. Seven (18%) had hyperplastic changes, ranging from simple hyperplasia through complex hyperplasia with atypia. The following prospective study was conducted: after breast surgery and prior to initiation of TAM therapy, an office endometrial sampling was obtained as a control. After initiation of TAM therapy, biopsies were repeated every 4 to 6 months as long as the patients remained asymptomatic. Nineteen patients were interviewed. Twelve patients were biopsied and followed from 3 to 15 months. One patient refused additional biopsies. Eleven patients had repeat biopsies after initiation of TAM. New hyperplastic changes were found in 3/11 (27%) patients. The preliminary results of this study (although with a small number of patients) indicate that TAM may have some neoplastic effect on the endometrium of postmenopausal patients with breast cancer. This study is still in progress. Additional prospective studies are warranted before a significant correlation between TAM and endometrial neoplasia is confirmed.
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PMID:Oncogenic potential of tamoxifen on endometria of postmenopausal women with breast cancer--preliminary report. 189 69

Acquired tamoxifen resistance represents a major cause of treatment failure in breast cancer. We implanted estrogen receptor-positive MCF-7 human breast cancer cells in athymic nude BALB/c mice as a model to study in vivo acquired tamoxifen resistance. After 4-6 months of tumor growth suppression by trans-tamoxifen, tumor progression was observed despite continued tamoxifen administration. Acquired resistance was not due to loss of estrogen receptors, to alterations in serum or tumor estrogen levels, or to changes in tamoxifen or its major metabolites in serum. Tamoxifen-resistant tumors remained estrogen dependent in vivo. However, resistance was also associated with the ability of tamoxifen to stimulate tumor growth. Resistant tumors were characterized by markedly lower intracellular tamoxifen levels and by isomerization of the potent antiestrogenic metabolite trans-4-hydroxy-tamoxifen to the less potent cis isomer. Metabolic tolerance, as manifested by alterations in cellular concentrations of tamoxifen and its metabolites, may thus be one mechanism for acquired tamoxifen resistance in breast cancer.
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PMID:Acquired tamoxifen resistance: correlation with reduced breast tumor levels of tamoxifen and isomerization of trans-4-hydroxytamoxifen. 192 Apr 88

Between 1965 and 1989, 46 desmoid tumors were observed in the hospitals of Lyon. Twenty-eight patients with an extra-abdominal tumor, with a follow-up of at least 6 months were observed. In this group, there were 12 males and 16 females with an average of 26.7 years. Surgical treatment was performed in 26 cases (in one case no treatment was given and in another case isolated chemotherapy was given). In 21 cases (80%) a recurrence of the tumor was seen after the first excision, incomplete in 6 cases. The highest rate of recurrence was seen in the neck, the girdles and the lower limbs; at the end of our review, 9 patients still had a tumor. No primary amputation were performed but two late amputations, one of which was major, were necessary. One tumor evolved into a sarcoma and in another case, lung metastases were seen. Associated radiotherapy was given in 9 cases with resolution in 55%. Tamoxifen was used in 5 cases with stabilization of the tumor. The risk of recurrence was higher in males (p = 0.0147). Age less than 30 years, and incomplete removal of the tumor were the other predictive factors for recurrence (the difference was not significant).
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PMID:[Extra-abdominal desmoid tumors. Therapeutic indications. Apropos of 28 cases]. 195 May 4

A case of recurrent retroperitoneal desmoid tumor successfully treated with tamoxifen (Nolvadex tablets, ICI Pharma, Division of ICI Americas, Wilmington, DE) is reported. The patient presented late in her second pregnancy with a large retroperitoneal pelvic desmoid tumor that was treated with surgical excision and megestrol acetate. When the tumor recurred 12 months later, it was again treated with surgery, this time followed by radiation therapy. The desmoid tumor quickly recurred. The patient was then treated with tamoxifen, resulting in a complete tumor regression that has remained stable for 27 months. Tamoxifen should be considered as first-line therapy in recurrent desmoid tumors.
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PMID:A recurrent pelvic desmoid tumor successfully treated with tamoxifen. 199 11

A sustained release of tamoxifen, which produced decreasing serum levels of this drug (24 to 4 ng/mL) over 6 months, suppressed mammary tumorigenesis in virgin or once pregnant C3H/OUJ female mice. Tamoxifen was consistently more effective than early ovariectomy, which only delayed tumorigenesis. Tamoxifen prevented the stimulatory action of cyclical (alternate-month) progesterone administration on mouse mammary tumorigenesis. However, when tamoxifen treatment (12 months) was stopped, progesterone treatment initiated tumorigenesis. In contrast, when long-term tamoxifen treatment was stopped in mice that had not undergone ovariectomy, and estrous cycle returned, the majority of these mice remained tumor free. A comparison of different durations (3, 6, and 12 months) of tamoxifen treatment of virgin mice, starting at approximately 4 months of age, showed an equivalent effect on mammary tumorigenesis. All virgin mice developed tumors by 18 months of age, whereas 80% of the tamoxifen-treated mice were tumor free. Nevertheless, cyclical progesterone administration caused rapid development of tumors after 3 months of tamoxifen treatment; only 15% of these mice were tumor free at 18 months. Cyclical progesterone administration caused an increase in tumorigenesis after 6 months of tamoxifen treatment; 50% of these mice were tumor free at 18 months of age. These data demonstrate the efficacy of tamoxifen to suppress mouse mammary tumorigenesis and demonstrate that continuous tamoxifen therapy is necessary to prevent the development of tumors by progesterone, a stimulatory hormone.
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PMID:Suppression of mouse mammary tumorigenesis by long-term tamoxifen therapy. 200 32

Although retroperitoneal fibrosis is uncommon and histologically benign, it is a progressive and potentially fatal tumor. As the fibroblasts proliferate, they encase and may obstruct important retroperitoneal structures. Medical therapy in the past has been ineffectual, and since the tumor usually cannot be resected, surgery consists of lysis or bypass of the involved structures. Tamoxifen is effective in the treatment of desmoid tumors, and we report its use in two patients with retroperitoneal fibrosis with excellent results. The simplicity and safety of this treatment make tamoxifen an attractive choice of therapy.
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PMID:The response of retroperitoneal fibrosis to tamoxifen. 200 55

The antiestrogen tamoxifen is the most widely used hormonal therapy for breast cancer. The drug exerts its antiproliferative effects primarily through estrogen receptor (ER)-mediated mechanisms, although other cellular actions may augment tumor inhibition. Clinically, tamoxifen has been less well studied in premenopausal than in postmenopausal patients. The drug has complex endocrine effects that are dependent on the treatment duration and dose, menopausal status, and target organ. In postmenopausal women receiving tamoxifen, serum estrogen levels remain low, and the normally elevated gonadotropin levels decrease. In contrast, serum estrogen levels are strikingly elevated in many premenopausal women, and gonadotropin concentrations are either unchanged or slightly increased. Large systematic trials in metastatic breast cancer have established tamoxifen as the recommended hormonal therapy for postmenopausal women with ER-positive tumors. Tamoxifen is also an active agent for premenopausal metastatic disease, and response rates are comparable to those reported for oophorectomy. Clinical experience with tamoxifen in this younger age group, however, is more limited. Few premenopausal women (less than 400) have been included in phase II and phase III trials. Two randomized trials (total of 160 patients) comparing oophorectomy with tamoxifen do not definitively establish therapeutic equivalence, and a survival advantage for either treatment cannot be excluded. Many questions remain concerning the appropriate role for tamoxifen in premenopausal patients. Still, tamoxifen has an attractive toxicity profile, and it offers a favorable therapeutic alternative for premenopausal women with ER-positive metastatic breast cancer who wish to avoid surgical or radiation castration.
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PMID:Tamoxifen in premenopausal patients with metastatic breast cancer: a review. 204 68

Foci, nodules of cellular overgrowth, that appear after confluence are an in vitro characteristic of malignant transformation. A well-studied in vitro model of estrogen-dependent tumors is the MCF-7 cell line, derived from a pleural metastasis of a human breast adenocarcinoma. We report that cultivation of MCF-7 cells, using routine methods, results in extensive estrogen-stimulated postconfluent cell accumulation characterized by discrete three-dimensional arrays. Side view Nomarski optical sections revealed these to be principally multicellular foci with occasional domes and pseudoacinar vacuoles. This effect on MCF-7 cell growth occurs in media containing fetal bovine serum but not with calf serum or charcoal-dextran-treated fetal bovine serum unless supplemented with estrogens. Foci formation starts 5-6 days after confluence, and the number of foci generated is a function of the concentration of added estrogens. Foci formation is suppressed by the antiestrogens Tamoxifen and LY 156758. Addition of progesterone, testosterone, or dexamethasone had little or no effect, while various estrogens (ethinyl estradiol, diethylstilbestrol, and moxestrol) induced foci development. Clones derived from single cells of the initial MCF-7 population revealed a wide variance in estrogen-induced foci formation, demonstrating heterogeneity of this tumor cell line. The postconfluent cell growth of the estrogen receptor-deficient cell line, MDA-MB-231, contrasted with MCF-7 by developing an extensive multilayer morphology devoid of discrete structures. The tumorigenic potential of the MCF-7 cells used in our experiments was confirmed by their estrogen-dependent growth in immunosuppressed male BDF1 mice. These data suggest an estrogen receptor-based mechanism for the development of multicellular foci during postconfluent growth of MCF-7 cells. After confluence, foci, in contrast to the quiescent surrounding monolayer, retain proliferating cells. Focus formation, therefore, reflects the heterogeneous responsiveness of these cells to estrogens and should provide a model permitting in vitro comparisons between the progenitor cells of multicellular foci and the monolayer population.
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PMID:Estrogen-stimulation of postconfluent cell accumulation and foci formation of human MCF-7 breast cancer cells. 205 45


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