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)

Seventy-two women with metastatic breast cancer were treated with multiple-agent chemotherapy. Fifty women were treated with 5 drugs in combination: 5-FU, methotrexate, vincristine, cytoxan, and prednisone; 22 were treated with the combination of 3 drugs: 5-fu, cytoxan, and prednisone. In 14 patients receiving 5 drugs and in 22 receiving 3 drugs, the multiple chemotherapy was the primary palliative treatment of extensive visceral metastases unsuitable for adrenalectomy. Results were similar with 6 responders in 14 (0.43) receiving 5 drugs, and 10 responders in 22 (0.45) receiving 3 drugs. The remaining 36 patients who were given 5-drug therapy all had previous adrenalectomy, and there were 16 responders (0.44). Toxicities from 3-drug treatment were substantially less severe than those from the 5-drug combination therapy. Whereas treatment-related death occurred in 6 of 50 patients receiving the 5-drug combination, no such incidence occurred in those receiving 3-drug combination therapy.
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PMID:Combination chemotherapy in the treatment of advanced breast cancer. 99 8

Corynebacterium parvum, a Gram-positive anaerobic bacillus thought to be a strong immunological stimulant, has been shown to decrease tumour growth and prolong survival in patients with metastatic disease. Study of the effect of a single injection of a strain of C. parvum (CN. 6134) in six patients with stage IV metastatic breast cancer is reported. Results of laboratory tests to judge the physical and immunological effects of the drug infusion 24 hr post-treatment and weekly thereafter for 3 weeks are evaluated. Within 24 hr after C. parvum administration, most patients experienced fever and nausea. Blood counts and differential counts exhibited increased values 24 hr after treatment with a strong shift to the left. Lymphocyte and monocyte counts were greatly depressed at 24 hr. T-cell numbers in peripheral blood did not appear to be altered, but the picture with regard to B cells was less clear. Normal count was recovered by day 8. It appears that intravenous administration of C. parvum produces a temporary marked immunological depression which returns to essentially normal values in 8 days. The return to normal may be accompanied by resolution of the endotoxin-like syndrome of side-effects. Further study of patients receiving this therapeutic agent is important to detect enhancement of the anti-tumour immunological response precipitated.
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PMID:The effect of Corynebacterium parvum on the humoral and cellular immune systems in patients with breast cancer. 108 21

Of 680 patients who had bilateral adrenalectomies for metastatic breast cancer, 583 were evaluable. Two hundred and nine patients (36 percent) responded (180 objective, 29 subjective responders) for at least 6 months. Age, menstrual status, prior response to oophorectomy, disease-free interval, involved organ systems, and incidental splenectomy were correlated with adrenalectomy response. Patients aged 21 to 35 years did poorly (23 percent response rate), whereas 41 percent of patients aged 51 to 65 responded. Menstrual status appeared to have no effect upon whether or not a patient responded to adrenalectomy. Oophorectomy responders benefited from adrenalectomy 40 percent of the time and oophorectomy failures responded in 27 percent of the cases. Patients with a disease-free interval of zero to 2.5 years responded to adrenalectomy at a rate of 31 percent whereas patients with a free interval greater than 2.5 years responded at a rate of 50 percent. When a single visceral organ or any combination of bone and soft tissue was involved, the average response rate was 39 percent. However, when multiple visceral organs or a single visceral organ with any combination of bone or soft tissue was involved, the response rate dropped to 26 percent. Sixty-six patients had splenectomies at the time of adrenalectomy with a 44 percent response rate, whereas nonsplenectomized patients had a 35 percent response rate. The median survival rate of 209 adrenalectomy responders was 26 months; it was 10 months for 374 nonresponders. The 5 and 10 year survival rates for adrenalectomy responders were 18 and 7 percent, respectively, and zero percent for adrenalectomy nonresponders. The patients who received greatest benefit from adrenalectomy in this series were aged 51 to 65 years, had a disease-free interval greater than 2.5 years and had metastases limited to a single visceral organ or any combination of bone and soft tissues.
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PMID:Bilateral adrenalectomy for advanced breast cancer: a 21 year experience. 114 43

Three prospectivelyly planned and controlled cooperative clinical studies in the use of combination drug therapy for metastatic breast cancer are reported. Each study contained two drug regimen arms. A total of 326 evaluable patients were treated with one of the five various drug combinations employed. As the number of drugs used in each regimen was increased from two to five, a concommitant increase in remission rates from 50% to 75% was observed. Remission duration of approximately 8 months and survival from the onset of treatment, however, remained relatively constant at 13 to 16 months in all drug regimens. Patients achieving tumor remission survived an average of three times longer than those with progressive disease under therapy. The results are correlated to patient age and predominant metastatic type. Subjective improvement was definitely related to objective tumor regression or stabilization. Treatment was relatively well tolerated and well applicable to outpatient care. Dosage adjustments were often necessary during the initial phases of therapy. Combined cystostatic drug therapy is highly effective in the prognostically worst forms of metastatic breast cancer, and is the treatment of choice for younger patients with visceral type metastases.
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PMID:A controlled study in the use of combined drug therapy for metastatic breast cancer. 117 24

Forty patients with metastatic breast cancer who had received no previous cytotoxic therapy were treated with a combination chemotherapy program CMF (P), which included methotrexate, 60 mg/m2, and 5-fluorouracil, 700 mg/m2 intravenously on the first and eighth days, in addition to cyclophosphamide, 100 mg/m2, and prednisone, 40 mg/m2, by mouth daily from the first to the fourteenth day of a 28-day cycle. Only 2 of 25 patients responded to hormonal therapy or endocrine ablation. Twenty-seven of the 40 patients (68%) had a complete response (8 patients) or partial response (19 patients). Lung, soft tissue, and nodal metastases were the most responsive sites. The median survival of 18 months for the responding group. The nonresponders had a median survival of 4 months. The toxicity was primarily hematologic and was especially severe in patients with functional liver impairment due to metastatic disease.
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PMID:Combination chemotherapy for advanced breast cancer: response and effect on survival. 125 83

Progesterone, like estrogens, is used in the treatment of metastatic breast cancer. The 3 most active derivatives are megestrol, norethisterone acetate, and medroxyprogesterone acetate (MPA). This study evaluates the use of MPA in treating metastatic breast cancer in 40 postmenopausal women (average age, 63 years; average duration of postmenopause, 14 years) who have either not responded to or have relapsed after therapy with estrogens and androgens. 18 patients received a depot preparation of MPA intramuscularly in a loading dose of 3.2 g over a 2-week period and then 400 mg at 2-4 week intervals. 22 patients received the drug orally in a dose of 200 to 300 mg daily. Patients were evaluated after 6 weeks of therapy. Criteria for evaluating response were those used by the Eastern Cooperative Oncology Group. Only 2 of 40 patients exhibited an objective response (disappearance of metastatic lymph node for 9 months in 1 and well-documented clinical improvement and control of brain metastases for 22 months in another). 2 patients had mixed responses of chest wall metastases (regression of some but not all lesions) lasting 3 and 4 months respectively. 5 patients had obvious subjective response (pain relief) but no objective response. Overall response rate was 22%: 4 objective responses (10%) and 5 subjectives responses (12%). Route of administration did not correlate with response. Tumor stimulation and clinical deterioration occurred in 4 patients. It appears that MPA therapy is costly and of minimal usefulness as secondary therapy in metastatic breast cancer. Further studies should focus on megestrol and norethisterone acetate which have been documented to have better response rates.
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PMID:Response to medroxyprogesterone acetate (NSC-26386) as secondary hormone therapy for metastatic breast cancer in postmenopausal women. 126 Jul 80

A series of 21 consecutive patients with carcinoma of the breast and symptomatic choroidal metastases was reviewed. All patients were symptomatic of choroidal metastases at presentation. Most patients had disease progression at other sites at the time of diagnosis. The incidence of cerebral metastases was not increased in this group compared to that in patients with metastatic breast cancer at other sites. Radiotherapy using a direct anterior field proved effective palliation for this disease site. Of the 32 eyes treated, serial visual acuity was documented in 23. Seventeen showed objective improvement and six showed stabilisation. The median duration of improvement was 11.5 months.
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PMID:Symptomatic choroidal metastases in breast cancer. 128 94

A panel of nine monoclonal and polyclonal antibodies were tested regarding specificity for metastatic breast cancer. A hundred metastatic tumors were stained, 50 of breast origin and 50 of other origins. Antibodies used were anti-alpha-lactalbumin, anti-lactoferrin, anti-casein, E29 (Dako-EMA), anti-secretory component, anti-gross cystic disease fluid protein (GCDFP15), BRST1, BRST2, and MC5. Analyses of the results were performed using chi-square and logistic regression. Positivity for MC5, BRST1, BRST2, lactoferrin, EMA, and GCDFP15 was significantly higher in tumors of breast origin than in others (p less than 0.05). Analyses of the whole panel indicated that GCDEP15 and MC5 were the best markers for identification of breast cancer metastases. When both were positive (58% of breast origin cases), the predicted probability of breast origin was 98%, compared to only 5% when both were negative. Comparison of anti-GCDFP15 with BRST2, a monoclonal antibody against the same protein, showed a slightly better sensitivity of the former, and a similar degree of specificity for breast tissue. In conclusion, a panel of antibodies can be used to securely differentiate metastatic breast cancer from other cancers in a large number of metastatic tumors of unknown origin.
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PMID:Immunohistochemical markers in the identification of metastatic breast cancer. 132 17

Epithelial mucins have obtained increasing clinical relevance since they were found in the serum of cancer patients and were shown to be elevated in metastatic disease. We report here the characterization of the monoclonal antibody (MAb) 436 which recognises the protein core of the polymorphic epithelial mucin (PEM) of the human breast. MAb 436 was generated by immunizing Balb/c mice with membrane-enriched fractions prepared from metastatic lesions in the axillary lymph nodes. The antigenic determinant recognized by the MAb 436 is expressed on the surface of breast cancer cells and was measured by ELISA on all of 50 cytosol preparations of primary breast tumors. Immunohistochemistry showed 98% of primary and 100% of metastatic breast cancer lesions to be positive with the 436 antigenic determinant expressed both in the cytoplasm and at the plasma membrane level of the tumor cells. Moreover, the antigen was expressed in a homogeneous fashion (80-100% of the total number of tumor cells) in more than 60% of the tumors. Reactivity with normal tissues was rare and scattered and restricted to glandular structures particularly at the luminal border level except for the distal and collecting tubules of adult and fetal kidney, where a cytoplasmic 436 antigen distribution was observed. Other cancers proved positive but the reactivity was always variable and heterogeneous. The antigen recognized by MAb 436 appears in Western Blotting as a M(r) of more than 200,000 daltons protein resolved in two bands. Epitope mapping experiments using overlapping octapeptides in the repeat unit of the PEM identified in the RPAP (Arg-Pro-Ala-Pro) sequence the binding site of the 436 antigen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of monoclonal antibody 436 recognizing the Arg-Pro-Ala-Pro sequence of the polymorphic epithelial mucin (PEM) protein core in breast carcinoma cells. 137 74

More than 45,000 women will die of metastatic breast cancer in the United States in 1991. Endocrine therapy remains a major option for treatment of such patients, and results in complete plus partial response rates of 30% with a median duration of approximately one year. Postmenopausal status, increased age, a prolonged disease-free interval, bone and soft tissue metastases, and positive estrogen and progesterone receptors are all associated with an increased response to endocrine therapy. The use of additive hormonal therapy, specifically antiestrogens, progestins, and aromatase inhibitors, have replaced surgical ablative procedures in the majority of patients; response rates to antiestrogen therapy, progestin therapy, and aromatase inhibitors are similar, but antiestrogens have generally been associated with the most favorable therapeutic index. At present, there is no convincing evidence that either combinations of endocrine therapies or endocrine therapy combined with chemotherapy are associated with an improvement in survival for patients with metastatic disease. Future research efforts directed at defining the molecular mechanisms of endocrine activity should facilitate clinical trials of newer and potentially more effective agents. All patients with metastatic breast cancer should be considered for at least one trial of endocrine therapy provided their metastatic disease is not rapidly progressive or life-threatening.
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PMID:Endocrine therapy for advanced breast cancer: a review. 138 23


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