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)

Between 1979 and 1983 56 women with stage I breast cancer underwent tumorectomy plus lymphadenectomy, postoperative irradiation and adjuvant antioestrogen therapy in cases of hormone receptor positive tumours. All patients with hormone receptor negative tumours received 6 cycles of combined CMF chemotherapy instead of antioestrogen therapy. It was possible to complete optimal dosage of CMF or tamoxifen in more than 85% of our patients. Leukopenia occurred in only 3 patients given chemotherapy, whilst intolerable gastrointestinal side effects occurred in 4 patients given antioestrogen therapy. No interference was detected between irradiation and chemo- or hormone therapy and no serious local complications with functional impairment were registered. 23% of the women had positive axillary nodes at the time of operation. The preoperative staging proved incorrect in 16% of cases, the tumour size exceeding 2 cm. After a mean follow-up period of 36 months the local recurrence rate was 3.6% and distant metastases appeared in 9% of patients, whereby there was a significant dependence on lymph node status. No patient died of cancer during the observation period. In view of the hypothesis that breast cancer is a systemic disease more attention should be paid to local cosmetic results and to systemic adjuvant therapy.
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PMID:[Experiences with an organ-saving and adjuvant-therapy concept in stage 1 breast cancers after 6 years of use within the scope of a controlled clinical study]. 300 63

Specific high affinity receptors for 1,25-dihydroxyvitamin D3 are present in several human breast cancer cell lines, and this hormone can regulate the replication of these cells. These receptors are also present in primary breast carcinomas. The present study has resulted from the follow-up for up to 68 mo of 263 women, who had had 1,25-dihydroxyvitamin D receptor (1,25-DR) levels measured in their primary tumors. Survival data on 191 women were correlated with the levels of 1,25-DR and other steroid hormone receptors, menopausal status, and age by life table analysis. Survival was not affected by 1,25-DR level in either absolute terms or relative levels. However, the late development of lymph node metastases in eight of 47 individuals was correlated with the 1,25-DR level (P = 0.05). There was no correlation between 1,25-DR or other hormone receptor levels and the development of hypercalcemia or bone metastases in the small number of individuals so affected. As we had observed previously, there was no correlation between the level of 1,25-DR and that of the other steroid hormones. These data show that the presence of 1,25-DR in primary breast cancers is independent of other prognostic indicators and, inasmuch as it correlated with late lymph node metastasis, may be an adverse prognostic indicator.
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PMID:Significance of 1,25-dihydroxyvitamin D3 receptor in primary breast cancers. 301 26

Epidermal growth factor (EGF-R) estrogen (ER) and progesterone (PR) receptors were evaluated in 89 primary breast cancers and 23 axillary lymph node metastases. About 57% of primary and 72.2% of metastatic tumors were EGF-R positive and median EGF-R levels were higher in metastatic deposits than in primary breast tumors (P less than 0.05). An inverse distribution of EGF-R and steroid hormone receptor positive tumors was found (chi 2 = 10.87; P less than 0.001 for PR and chi 2 = 5.01; P less than 0.05 for ER) and an interesting correlation between EGF-R expression in primary tumor and axillary lymph node involvement was demonstrated (chi 2 = 21.4; P less than 0.001). Immunohistochemical studies with a monoclonal antibody against EGF-R revealed the presence of EGF-R only in malignant cells. Our data suggest that EGF-R could identify a class of more aggressive breast tumors endowed with a higher metastatic potential and may therefore represent an unfavorable prognostic parameter in breast cancer.
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PMID:Epidermal growth factor receptor in human breast cancer: correlation with steroid hormone receptors and axillary lymph node involvement. 306 25

While hormone receptor values are extremely valuable in breast cancer management, many variables leading to falsely negative receptor results should be considered before clinical decision making in the setting of metastatic disease. At the Papanicolaou Comprehensive Cancer Center in Miami, Florida 271 patients with metastatic breast cancer received tamoxifen over a 4-year period. Only 40 of the 204 patients (19.6%) with available estrogen receptor assay information had pretreatment receptor values classically considered receptor-poor. While four patients had inevaluable tamoxifen trials and 12 patients had "compassionate" use in end-stage situations, 24 patients received tamoxifen therapy in the face of receptor-poor values because of clinical or histopathological correlates suggesting the possibility of false negative assay results. Six of 36 evaluable patients (16.6%), including those treated on "compassionate grounds," responded to tamoxifen, while 6 of 24 more highly selected patients (25%) responded. Response durations in these six patients were 11, 12, 28, 28+, 49, and 51 months, respectively; two of these six also had significant, objective tamoxifen withdrawal responses of 9 and 14 months. Based on these results, it is urged that receptor values are studied and integrated with classical clinical and histopathologic variables before making a clinical decision so that patients with receptor-poor assay results are not prematurely labeled hormonally unresponsive.
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PMID:Response to tamoxifen in estrogen receptor-poor metastatic breast cancer. 330 11

The survival of 193 premenopausal breast cancer patients was analyzed in terms of onset of use of oral contraceptives: earlier use of pills predicted shorter survival times. 193 consecutive breast cancer premenopausal patients, from the southern region of Sweden diagnosed at University of Lund, were staged and interviewed for age when starting pills, duration, and brand. Women who started orals before age 20 had significantly shorter survival rates than never-users or late users (p=0.02 and 0.04). Women who started orals between 20-25 years of age showed a tendency toward shorter survival compared to never users (p=0.18). The relative risks, adjusted for age at diagnosis, increased in proportion to earlier age of onset of pill use (never = 1.0; 25 = 0.7; 20-25 = 2.8; 20 = 9.2). When only cancer stages II and II were considered in a multivariate model, a significantly elevated risk appeared for early users regardless of age or treatment given. The estrogen and progesterone receptor concentrations in the primary tumor were significantly lower among early users (p=0.001 and 0.05). These findings are consistent with previously reported larger tumor size, higher frequency of axillary metastases and altered hormone receptor status in early pill users.
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PMID:Early oral contraceptive use as a prognostic factor in breast cancer. 335 38

We review the biology and biochemical pharmacology of four antifolates that were recently introduced into clinical trial as anticancer agents, and one compound in preclinical development. Toxicology and clinical data are not discussed. 10-Ethyl-10-deazaaminopterin (10-EdAM) is a classical antifolate, structurally related to methotrexate (MTX) but with greater activity against murine tumors. 10-EdAM has more efficient membrane transport, and relatively greater polyglutamylation in murine tumors than in normal mouse tissues, and these differential effects are greater for 10-EdAM than for other 10-deaza antifolates or for MTX. Trimetrexate and piritrexim are nonclassical antifolates, lacking a glutamate substitution. They are lipophilic, cross cell membranes more rapidly than does MTX, and retain activity against tumors resistant to MTX because of impaired drug transport. These nonclassical antifolates are active against several MTX-insensitive murine tumors, and both have demonstrated clinical anticancer activity. 10-EdAM, trimetrexate and piritrexim all inhibit dihydrofolate reductase (DHFR) as their primary site of action. As such, they deplete cellular thymidylate and purine pools, and inhibit DNA replication. N10-Propargyl-5,8-dideazafolic acid (CB3717) differs from the first three compounds in acting primarily on thymidylate synthase. Like DHFR inhibitors, it blocks DNA replication through depletion of dTTP, but it does not exert an antipurine effect. CB3717 retains activity against transport-defective MTX-resistant cells, and also against cells that overproduce DHFR. 5,10-Dideazatetrahydrofolic acid (DDATHF) is a selective inhibitor of glycinamide ribotide transformylase, and its biochemical pharmacology may differ appreciably from that of the other antifolates under study. DDATHF has strong antitumor activity in several murine systems.
Cancer Metastasis Rev 1987
PMID:Biological and biochemical properties of new anticancer folate antagonists. 354 36

Stage, estrogen receptor status, treatment and survival of 29 men with breast cancer attending the Breast Clinic of the Johannesburg Hospital between 1976 and 1985 are reviewed. Most patients had locoregionally advanced disease at presentation. Estrogen receptors (ER) were detected in significant concentration in 15/23 (65%). Local control was achieved in the majority, 19/26 (73%), by either surgery or radiation therapy alone or by combined modality treatment. Fifteen of 23 patients tested (65%) were ER-positive (greater than 10 fmol/mg protein). For patients with metastatic disease hormone receptor status was predictive of response to hormonal manipulation. Tamoxifen was the most acceptable and frequently used form of hormone therapy with 7/12 patients responding. Combination chemotherapy gave a response rate comparable to that seen in women with breast cancer.
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PMID:Breast cancer in men. Clinical features, hormone receptor status, and response to therapy. 362 Nov 16

Clinical course of 77 surgical cases of cancer of the large bowel was evaluated versus levels of estrogen, androgen, progesterone and glucocorticoid hormone receptors. Within the follow-up period (range 6-41 months), 7 (9%) patients died of tumor progression, 16 (21%) developed recurrence or metastases, while the rest 54 (70%) cases continued in remission. Patients with steroid hormone receptor-positive tumors revealed more favorable clinical course as well as longer disease-free and overall survival than cases of receptor-negative cancer. Estrogen receptor status was found to be of the highest prognostic value in terms of clinical course and survival, as compared to all other hormone receptors studied.
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PMID:[Prognostic value of the level of steroid hormone receptors in cancer of the large intestine]. 366 Jul 56

The DNA labelling index (LI), representing the fraction of S-phase cells, was studied in 76 patients operated on for breast cancer from 1975 to 1979. No patient had lymph node involvement following axillary dissection (N-), and no adjuvant medical treatment was given. Patients were classified in one of two groups according to the median LI. Patient distribution by age, tumour size, and receptor status was identical in both groups. A higher frequency of grade 3 tumours was noted in the group with an LI above the median value. The cell proliferation rate was an important discriminative factor for metastatic potential. The probability of survival at 8 years for patients with a high LI was significantly lower than that of patients with low LI (36% versus 100%; p less than 0.001). Relapse-free survival at 8 years was respectively 56% and 83% (p less than 0.02). At 2 years, these values were 75% and 100%, indicating the early occurrence of metastases. By contrast, the LI had no prognostic value concerning loco-regional disease recurrence or survival after the appearance of metastasis. No relationship was found in this study between survival and other prognostic factors, namely tumour size, histological grade, or hormone receptor level. The LI currently appears to be the best prognostic factor for N- breast cancer. High risk patients identified by this method could thus be offered adjuvant medical treatment.
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PMID:The DNA labelling index: a prognostic factor in node-negative breast cancer. 366 56

The optimal dose of progesterone compounds for the treatment of breast cancer is unknown, but there is evidence to suggest a dose-response curve. We are testing the tolerability and efficacy of megestrol acetate administered orally and continuously in doses three to ten times higher than the standard dose of 160 mg/d. We have so far treated 33 patients with metastatic breast cancer and positive or unknown tumor hormone receptor status. Thirty patients had had documented disease progression with previous hormonal therapy, and 22 had failed with previous chemotherapy. Twenty-five patients had objectively measurable metastases. In this heavily pretreated group, the objective response rate was 40%; in addition, 32% of patients had stabilization of disease. Interestingly, ten of 12 patients who had developed disease progression while on standard-dose megestrol acetate therapy had objective response or stabilization on the higher dose. Toxicity was acceptable and reversible and included mild elevations of blood pressure and weight gain. Our results indicate that high-dose megestrol acetate is well-tolerated and highly active in advanced refractory breast cancer, and suggest a dose-response curve for the drug in the treatment of breast cancer.
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PMID:High-dose megestrol acetate in the treatment of postmenopausal women with advanced breast cancer. 379 25


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