Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a double-agar clonogenic system adapted to human breast cancer. We optimized the conditions for cell growth and clonogenicity with respect to hormones (insulin, estradiol, progesterone) and components of the extracellular matrix (collagen, laminin and fibronectin). Using our experimental improvements, 67% of the breast tumor samples received were grown successfully. Tests on 21 tumors with three agents: Doxorubicin, Methotrexate and 5-Fluorouracil permit objective discrimination of the in vitro pharmacosensitivity of human breast tumors. Flow cytometric analysis reveal that 64% of the tumors were diploid and 36% were aneuploid. The aneuploid tumors grew better in the double agar layer system used for the clonogenic assay. The diploid tumors were especially rich in estrogen (ER+) and progesterone (PR+) receptors whereas the aneuploid tumors were mostly estrogen and progesterone receptors negative (ER-/PR-). Finally, we noted no difference in drug responsiveness depending on the tumor ploidy and steroid receptor content.
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PMID:Flow cytometric analysis of human breast tumors and assessment of in vitro chemosensitivity by clonogenic assays. 233 69

In 34 patients with primary advanced breast cancer, intra-arterial administration of ADR (50 mg X 3, total dose 150 mg, 10 cases), 4' epi ADR (50 mg X 3, 150 mg, 8 cases; 70 mg X 3, 210 mg, 10 cases) and THP-ADR (50 mg X 3, 150 mg, 6 cases) was performed, and its effects and side effect were analyzed. The clinical and histological response rate were superior in the ADR (150 mg) regimen and 4'-epi-ADR (150 mg) regimen. Signs of systemic toxicity such as gastrointestinal disorders, leukocytopenia and thrombocytopenia were the side effects in patients treated with THP-ADR, but the frequency of alopecia was lower. No cardiotoxicity was recorded in any of the patients. These results indicated that 4'-epi-ADR given the total dose of 150 mg in a single dosage of 50 mg was the most effective agent in intra-arterial infusion chemotherapy for advanced breast cancer.
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PMID:[Intra-arterial infusion chemotherapy of advanced breast cancer--effects and side effects of adriamycin, 4'-epi-adriamycin and THP-adriamycin]. 278 5

Twenty evaluable patients with primary or secondary neoplastic liver involvement received FUDR (0.2 to 0.3 mg/kg per day) by continuous infusion to the hepatic artery for 14 days, every 4 weeks, through a surgically implanted Infusaid (USA) pump. In addition to FUDR, MMC (15 mg/m2 every 6 to 8 weeks) was given to 14 patients with colorectal cancer and one patient with breast cancer, and ADR, (40 mg/m2 every 4 to 6 weeks) was given to 5 patients with hepatocellular carcinoma. MMC and ADR were given as a bolus injection, through the pump sideport. Radiation therapy to the liver (2,000 rads in fractions of 180 to 200 rads each) was given to eight patients with colorectal carcinoma. In total, the 20 patients received 218 months of treatment and 580 injections. The overall remission rate (complete, partial and minor response) was 55%; one patient with a colorectal carcinoma achieved a CR and seven patients (35%) a PR; three patients (15%) had a MR, and in eight patients (40%) stabilization of disease was observed. Overall median survival was 12 months: 15.5 months for colorectal cancer patients and 7.5 months for patients with hepatocellular carcinoma. Toxicity consisted mainly of chemical hepatitis, mild to severe peptic disease and sclerosing cholangitis. Hematological toxicity was not observed. These data suggest that chemotherapy through the hepatic artery, while still experimental, may be considered for selected patients with tumor confined to the liver.
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PMID:Treatment of primary and metastatic liver cancer using an implantable chemoinfusion pump. 284 96

Between 1976 and 1982, 59 patients with locally advanced breast cancer were treated with preoperative supervoltage radiotherapy, adjuvant preoperative and postoperative hormonochemotherapy, and modified radical mastectomy. Systemic treatment, which was started simultaneously with radiotherapy, consisted of a combination of daily oral tamoxifen and a monthly alternation of Doxorubicin + vincristine and cyclophosphamide + methotrexate + 5-fluorouracil (CMF). One of each cycle was given preoperatively at half dosage and five of each were repeated postoperatively at full dosage. All patients became operable. Results of pathologic examination of the operative specimen, available in 51 patients, showed complete disappearance of tumor tissue in breast areas in eight patients, of which three still had positive axillary nodes. After a median follow-up time of 6 years locoregional failure was observed in 12 patients (20%) but in only three (5%) did it occur before distant failure. The actuarial median survival of the entire patient population is close to 4 years. Seven patients are alive without recurrence at greater than 9 years. This aggressive multidisciplinary treatment approach is associated with a projected 30% long-term survival (10 years), excellent local control, but substantial toxicity.
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PMID:Six-year results of a multimodality treatment strategy for locally advanced breast cancer. 314 77

Doxorubicin and its epimerized analog epirubicin were tested at a dose of 75 mg/m2 given iv every 3 weeks to 42 patients with advanced breast cancer, 23 of whom were in relapse from prior cyclophosphamide, methotrexate, and 5-FU (CMF) chemotherapy. The median cumulative dose was 540 mg/m2 (range, 225-650) for doxorubicin and 565 mg/m2 (range, 150-600) for epirubicin. Complete plus partial response was documented in 11 of 21 patients (52%) following doxorubicin and in 13 of 21 patients (62%) following epirubicin. The median observation period was 22 months (range, 14-30); the median duration of response and the median survival were superimposable. Doxorubicin and epirubicin exhibited a superior response rate in previously untreated patients [six of eight (75%) vs eight of 11 (73%)] compared to those previously given CMF with or without endocrine therapy [five of 13 (38%) vs five of ten (50%)]. Vomiting, mucositis, and leukopenia were documented less frequently following administration of epirubicin as compared to doxorubicin. Regarding cardiac evaluation, no significant differences were evident between the two drugs. However, a significant fall in the left ventricular ejection fraction was documented in women who received doxorubicin following a cumulative dose greater than 550 mg/m2. Following completion of doxorubicin therapy at cumulative doses of 580 and 562 mg/m2, two women developed left ventricular failure at 6 and 14 months, respectively. Epirubicin appears to be an effective drug for the treatment of breast cancer and, given at equal doses, is less toxic than doxorubicin.
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PMID:Phase II study of doxorubicin versus epirubicin in advanced breast cancer. 345 71

About 80% of patients with breast cancer ultimately die of metastatic disease at 20 years. Distant metastases are more important as a cause of death than local or regional relapses. It is for this reason that adjuvant chemotherapy is necessary, especially in young patients and those with extensive disease. Initial chemotherapy preceding any local or regional treatment is justified on the grounds that both surgery and anaesthesia lead to immunodepression. Further, the value of initial chemotherapy has been demonstrated in many experimental and clinical trials by Nissen-Meyer, Bonadonna and Cooper (1-3). In the present study 145 patients, including 67 with inflammatory breast cancer (IBC), were treated with 4-6 weeks of Velbe, thiotepa, methotrexate, fluorouracil and prednisone, with Adriblastin added for patients with IBC, T greater than 7 cm, or N2, N3. Because of tumour regression of greater than 50% observed in 80% of the patients, the majority (123 patients) then received radiotherapy alone (cobalt + iridium), resulting in complete remission in all these cases. Maintenance treatment with the same drugs was prescribed for 6-18 months depending on the initial stage. Tumour regression appears to be an important prognostic factor. Median follow-up is only 17 months, the longest being 42 months. Overall survival at 2 years for IBC is 90%, with a disease-free survival of 80%. Cosmetic results are excellent. While these results are encouraging, longer follow-up is needed to confirm this improvement.
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PMID:Neoadjuvant chemotherapy of breast cancer. 352 69

Seven hundred and ninety-six consecutive patients with operable primary breast cancer treated with doxorubicin-containing postoperative adjuvant chemotherapy between 1974 and 1982 were evaluated for assessment of the acute and long-term toxicities of the program. Most patients experienced nausea, vomiting, and alopecia, side effects that were totally reversible. Doxorubicin skin infiltration was observed in 6% of the patients. Hematologic toxicity was moderate, and only 26% of the patients had a granulocyte nadir of less than 1000 cells/ml. Febrile or infectious complications occurred in 6% of patients, of which 3% required hospitalization for observation and antibiotic treatment. No long-term hematologic changes were observed. Amenorrhea was reported by 80% of premenopausal patients. However, none of the patients under 30 years of age had menstrual abnormalities, whereas 96% of those 40-49 years of age developed amenorrhea. Amenorrhea was permanent for most women over 40, but for 50% of patients under 40 years of age, it was reversible. Endocrinologic studies showed that amenorrhea was a result of primary ovarian failure. The incidence of second malignant neoplasms was lower (1.3%) in the group treated with 5-fluorouracil, doxorubicin, and cyclophosphamide than in the historical control group (4.8%). Cardiac toxicity data was evaluated in 460 patients. When up to a cumulative dose of 300 mg/m2 was given, 1% of the patients developed congestive heart failure. In 4 of these 5, adequate control was achieved with medical treatment; 1 patient died as a consequence of cardiac toxicity.
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PMID:Immediate and long-term toxicity of adjuvant chemotherapy regimens containing doxorubicin in trials at M.D. Anderson Hospital and Tumor Institute. 353 81

Thirty-nine patients with locally advanced breast cancer (T3b-4, N1-3 or inflammatory carcinoma) received 3 cycles of induction chemotherapy with estrogenic recruitment before surgery. The therapeutic regimen consisted of diethylstilbestrol (DES) orally on days 1-3, 5-Fluorouracil + Doxorubicin + Cyclophosphamide on day 4 q 21 days (DES-FAC). After surgery 6 additional cycles of chemotherapy (3 DES-FAC alternating with 3 DES-CMF with Methotrexate + F and C as in FAC) were administered. The objective response rate was 71.8% with 15.4% CR, and 56.4% PR; after surgery 36/39 (92.3%) patients were rendered disease-free. So far, 13 of 26 patients in stage IIIb have relapsed (9 of 13 with inflammatory carcinomas). Three-year survival and progression-free survival are 60% and 53.5%, respectively. Twenty-three of the 39 patients were subjected to serial tumor biopsies during the first DES-FAC regimen to allow for tumor-cell kinetic studies during DES and chemotherapy. A significant estrogenic recruitment occurred in 16 patients (69.6%), irrespective of estrogen-receptor status. At surgery, 3-4 weeks after induction chemotherapy, tumor proliferative activity was significantly depressed in comparison to basal values. These results indicate that breast cancer cells can be recruited in vivo with DES and that chemotherapy following estrogenic stimulation is effective and feasible with acceptable toxicity.
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PMID:Chemotherapy with estrogenic recruitment and surgery in locally advanced breast cancer: clinical and cytokinetic results. 366 87

One mechanism by which drugs alter the function of enzymes is through chronic inhibition. To determine whether commonly used cancer chemotherapeutic agents could alter protein kinase C (PKC) and thereby modify the calcium-messenger system, we studied the effect of anthracyclines and vinca alkaloids on the activity of PKC. Doxorubicin, daunomycin, vincristine and vinblastine inhibited the activity of PKC by 50% at concentrations of 150, 120, 350 and 140 microM respectively. Furthermore, we demonstrated the potential for this interaction to occur in intact cells, since doxorubicin blocked the binding of the phorbol ester, PDBu, to its receptor, PKC. The mode of inhibition of PKC was due, at least in part, to interference with the activation of the enzyme by phosphatidylserine. The activity of PKC was increased 15 fold in a highly resistant human breast cancer line, but this increase in enzymic activity was not seen in all lines tested. These studies demonstrate that anthracyclines and vinca alkaloids inhibit PKC, and suggest that chronic antagonism could lead to changes in its activity and function.
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PMID:Inhibition of protein kinase C by antineoplastic agents: implications for drug resistance. 368 68

Sixty-four patients with advanced progressive breast cancer resistant to conventional treatments were entered into the present study. They were randomized to receive either Carminomycin (CMM) 20 mg/m2 or Doxorubicin (DOX) 75 mg/m2, both drugs being administered by i.v. bolus every 3 weeks until progression of the disease. Five patients were not eligible and response could not be evaluated in another eight patients. Three patients had only one course due to disease-related early death. Among twenty-seven evaluable patients who received at least two courses of DOX one complete response and seven partial responses were observed for an overall response rate of 30%. CMM showed significantly lower (P = 0.04) antitumor activity with only one partial response (4%) among the 24 patients who received at least two courses of therapy. Median duration of response dating from the start of chemotherapy was 46 weeks on DOX (range 18-102+) and 30 weeks for the single partial response on CMM. Although the median time to progression for all patients receiving CMM (9 weeks) was significantly shorter (P = 0.04) than for those receiving DOX (30 weeks), patients on DOX had only a marginally longer duration of survival (P = .28) than those initially treated with CMM. Myelotoxicity was more severe in the CMM treated group than in the DOX group. Other toxicities such as alopecia, nausea and vomiting were slightly more severe in the DOX treated group. On the basis of this and other similar randomized studies, CMM cannot be recommended for further application in the treatment of advanced breast cancer.
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PMID:Carminomycin versus doxorubicin in advanced breast cancer, a randomized phase II study of the E.O.R.T.C. Breast Cancer Cooperative Group. 377 31


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