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)

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

Results of adjuvant hormone therapy with Tamoxifen, an antioestrogenic substance, have been discussed. 82 patients in 2 groups who were diagnosed with metastatic mammary carcinoma received Tamoxifen (ICI) and Tamoxifen (Ebewe) orally in a dosage of 20 to 40 mg/day. 43% of the patients in group A (Tamoxifen, ICI) experienced complete or partial remission of the metastases. In group B (Tamoxifen, Ebewe), this result was achieved in 54% of cases. The better results were due to the fact that the disease was not so advanced in the group B patients and they were also longer in the menopause. Thus in terms of efficacy, the preparations are identical. Severe side effects due to the therapy were not observed.
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PMID:[The treatment of metastasizing breast carcinoma using antiestrogens]. 192 78

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

Two hundred 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, Columbus, OH), and radiation therapy as exclusive locoregional treatment. Tamoxifen was given to 195 patients (130 postmenopausal and 65 premenopausal) and was omitted in 55 patients (31 postmenopausal and 24 premenopausal). There were 19 Stage I, 86 Stage IIA, 51 Stage IIB, 36 Stage IIIA, and 58 Stage IIIB patients. 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-year disease-free survival (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. The actuarial rate of locoregional recurrence was 13% for T2, 18% for T3, and 19% for T4. At 5 years the rate of breast preservation was 94%. Cosmetic results were excellent or good for most patients. The 5-year overall survival (OS) rates were 95% for Stage I, 94% for Stage IIA, 80% for Stage IIB, 60% for Stage IIIA, and 58% for Stage IIIB. Most patients with breast cancer should be given the option of breast-preserving treatment.
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PMID:Results of neoadjuvant chemotherapy and radiation therapy in the breast-conserving treatment of 250 patients with all stages of infiltrative breast cancer. 211 76

Tamoxifen, an antiestrogen with efficacy in treatment of both estrogen receptor-positive and negative breast tumors, may be immunomodulatory. We tested tamoxifen's ability to augment the antitumor activity of interleukin-2 (IL-2), a lymphokine capable of expanding and activating lymphocytes, in the treatment of established pulmonary metastases of the weakly immunogenic murine fibrosarcoma MCA-106. Age-matched C57BL/6 female mice bearing pulmonary metastases induced by a tail vein injection of MCA-106 tumor suspension (5 x 10(5) cells/mouse) were treated from days 3 through 12 with intraperitoneal saline solution or IL-2 (50,000 units twice a day). Half of the mice in each group received plain and the remainder received tamoxifen-treated (2 units/ml) drinking water ad libitum for the duration of the experiment. All mice were killed on day 18 for enumeration of pulmonary metastases. Compared with saline-treated control mice, IL-2 and tamoxifen reduced metastases by 66% (p less than 0.0002) and 30% (p less than 0.005), respectively. IL-2 and tamoxifen combined reduced metastases 95% (p less than 0.0002), significantly better than did IL-2 (p less than 0.02) or tamoxifen (p less than 0.0003) alone. In vitro, tamoxifen inhibited proliferation of the weakly estrogen receptor-positive MCA-106 tumor by approximately 30%. Tamoxifen had no effect on the generation of 3-day IL-2-activated lymphocyte cytotoxicity against both natural killer-sensitive (YAC) and natural killer-resistant (MCA-106) target cells. Both YAC and MCA-106 tumor became more resistant to lysis with increased concentration of tamoxifen. This is the first demonstration of in vivo potentiation of IL-2 antitumor activity by tamoxifen and suggests its possible use clinically.
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PMID:Tamoxifen potentiates in vivo antitumor activity of interleukin-2. 238 15

One of two patients with systemic metastases from a poorly differentiated eccrine adenocarcinoma of the scalp was found to have a tumor positive for estradiol receptors. In the receptor positive patient, after tamoxifen therapy, the lymph node metastasis regressed completely and was associated with full relief of pain from osseous metastases for nearly 3 years. Subsequently, progressive painful osseous metastases in the spine, skull, pelvis, and femur were palliated for shorter periods with sequential systemic therapy with megestrol acetate and fluoxymesterone. Osseous metastases were also palliated with external radiation therapy. In contrast, despite external radiation therapy, brain metastases proved fatal. Tamoxifen was ineffective in the estradiol receptor negative patient. Based on this report, it may be valuable to determine the presence of estradiol receptor protein in eccrine carcinoma as a predictor of response to hormonal therapy.
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PMID:Response of eccrine adenocarcinoma to tamoxifen. 273 82

Testosterone is a known estrogen precursor especially in postmenopausal women. Tamoxifen, an anti-estrogen, is used in the treatment of women with breast cancer in whom metastatic disease has been demonstrated. The action of Tamoxifen is thought to be to occupy the intracellular estrogen receptor sites in target tissues and thus block the action of the biologically active estrogen, estradiol. Effects of Tamoxifen on the production and metabolism of hormones have been postulated. We studied the kinetics of testosterone metabolism by the constant infusion of 3H-testosterone in six postmenopausal women with breast cancer prior to and during Tamoxifen therapy. The Tamoxifen did not produce any significant change in the metabolic clearance rate, the plasma concentration or the calculated blood production rate of testosterone. The only significant alteration in the conversion ratio of testosterone to metabolites was the reduction (p less than 0.02) in conversion to 5 alpha-dihydrotestosterone. A significant reduction in the plasma concentrations (p less than 0.05) of dehydroepiandrosterone and of luteinizing hormone (p less than 0.02) was found. Other steroid and peptide hormones did not show any significant changes. We conclude that Tamoxifen therapy has very little effect on the kinetics of testosterone metabolism in postmenopausal women with metastatic breast cancer.
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PMID:Effects of tamoxifen on testosterone metabolism in postmenopausal women with breast cancer. 293 65

Tamoxifen, an antiestrogen, is a competitive inhibitor of estradiol, blocking its effects on the target organs. During the 10 years it has been used in the United States it has become preferred over estrogens for treating postmenopausal women with metastatic breast cancer. Recently, tamoxifen has been used in treating premenopausal women with recurrent breast cancer, and its efficacy has been proved equal to that of ovarian ablation. In comparative trials, tamoxifen has been as effective as alternative endocrine treatments, and has greatly reduced toxicity and no irreversible side effects. Because of the high risk for systemic relapse in patients with breast cancer with regional lymph node metastases, (stage II), tamoxifen has been evaluated as adjuvant therapy after local treatment of the tumor. The results of these trials have shown a significant increase in the disease-free survival of postmenopausal women treated with tamoxifen, particularly in patients with hormone-receptor-positive tumors. Tamoxifen has not been as useful as adjuvant treatment in premenopausal women, for whom combination chemotherapy is the treatment of choice.
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PMID:Tamoxifen in the treatment of breast cancer. 329 59

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

It is correct to add hormone or chemotherapy in advanced metastatic disease of endometrial carcinoma and in recurrences. Large doses of hormone treatment have to be given. These are progestagens and the success rate with them, no matter which product is used, is approximately 30%. The use is limited by high blood pressure and the risks of vascular complications and metabolic upsets. Tamoxifen seems to the better tolerated and gives similar results. The response to hormone treatment depends on how sensitive the tumor is to the hormones. It is better when it has large numbers of progesterone receptors and it is of low grade. When the tumour is resistant to hormones, chemotherapy with cytotoxic drugs should be used. These drugs are adriamycine and mono or combined chemotherapy, but there is no protocol as yet that is better than any other. The debate about whether to use adjuvant treatment in stage I or II cases is open. It must be considered when the prognosis seems to be bad or there seem to be large risks of recurrences.
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PMID:[Hormone therapy and chemotherapy of endometrial cancer]. 333 Jul 33


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