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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adjuvant chemotherapy of early breast cancer in premenopausal women has nearly reached the point where it can be said with confidence that the relapse-free survival rate, as well as overall survival rate, is being lengthened, especially when drug combinations are used. In postmenopausal women, however, adjuvant chemotherapy has not consistently improved the relapse-free rate. Some investigators have postulated that postmenopausal patients do not respond as well to chemotherapy as their premenopausal counterparts because they usually receive lower doses. Thus, trials of these drugs at doses that more closely approximate the calculated dose are needed in postmenopausal patients. Recent advances in determination of estrogen and progesterone receptors in breast cancer cells have allowed effective use of adjuvant hormone therapy instead of or in addition to chemotherapy in some patients with early disease. However, further investigation of the role of hormone manipulation in breast cancer is also needed. Adjuvant chemotherapy of advanced breast cancer, however, is only palliative; duration of relapse-free and overall survival is not nearly as long as in early disease. Hormone therapy has been effective as initial treatment in patients with positive estrogen and/or progesterone receptors. Alternative treatments under investigation include use of new anthracycline derivatives, high-dose single agents, and biomodulation with interferon and Staphylococcus aureus protein A. Thus, while advanced breast cancer is not now curable, the wide range of effective agents and promising new approaches to treatment certainly justify some optimism for the future.
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PMID:Breast cancer treatment--current status. 4. Adjuvant therapy. 619 3

Infection of 13 month-old C3H mice with EMC virus or inoculation with the interferon inducer poly(I)poly(C) results in elevated levels of the enzyme 2',5' oligo(A) synthetase only in animals with spontaneous tumors (breast cancer or hepatomas). High enzymatic activities are detected in homogenates from liver, spleen, plasma and neoplastic cells of the animals with breast carcinomas and only in the neoplastic liver cells of the animals with hepatomas.
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PMID:Induction of 2',5' oligo(A) synthetase in tumor-bearing mice with encephalomyocarditis (EMC) virus or poly(I)poly(C). 631 39

A cooperative phase I-II study of HLBI (human lymphoblastoid interferon), natural interferon-alpha, was carried out in 38 major institutions in Japan. The eligibility of patients and evaluation of tumor response were based on the 'Criteria for the Evaluation of Clinical Effects of Cancer Chemotherapy on Solid Tumor' by Koyama and Saito, and on Blood Cancer by Kimura. Major objectives of the phase I study were pharmacokinetics and toxicity of HLBI . Based on the toxicity observed in 5 patients with advanced breast cancer, the maximum tolerated dose (MTD) was determined to be 12 X 10(6) unit/day for 1 month. In phase II study, HLBI was administered by i.m. injection at a dose of 3-6 X 10(6) unit/day. Out of 391 patients entered into this study, 280 patients were evaluable. Complete and partial responses were observed in 40 (14.3%) out of 280 evaluable patients, including 11 (19.6%) out of 56 renal cell cancers, 14 (19.2%) out of 73 multiple myelomas, and 9 (17.3%) out of 52 malignant lymphomas among others. Major side effects were fever (69.8%), gastrointestinal disturbances (31.4%), leukopenia (30.7%), thrombocytopenia (27.8%), hepatotoxicities (23.6%) and general fatigue (22.1%).
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PMID:[A cooperative phase I-II study of HLBI in patients with malignant tumors]. 632 4

Nineteen patients with advanced refractory metastatic breast cancer no longer responsive to chemotherapy were treated in the first phase II efficacy trial of recombinant leukocyte A interferon (IFL-rA), a highly purified single molecular species of alpha interferon prepared by recombinant DNA methods. Patients received a previously determined maximum tolerated dose for this agent (50 X 10(6) U/m2 body surface area) by intramuscular injection three times weekly for up to 3 months. The symptoms of toxicity observed in this trial resemble those previously reported for alpha interferons and include fever, chills, fatigue, anorexia, and leukopenia. All patients required dose reductions, most often for reasons of severe fatigue. Of the 17 patients evaluable for tumor response, one patient had stable disease and 16 had evidence of tumor progression. We conclude that IFL-rA is not an active agent in the treatment of advanced, refractory breast cancer when used at a maximum tolerated dose on this treatment schedule.
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PMID:Recombinant leukocyte A interferon in advanced breast cancer. Results of a phase II efficacy trial. 634 90

A clinical study on human lymphoblastoid interferon (HLBI) in various advanced malignant diseases was performed. HLBI was administered to a total of 25 patients with various advanced malignant diseases in order ot investigate antitumor effect and toxicity. The diseases evaluated were as follows: 8 multiple myeloma (MM), 2 chronic lymphocytic leukemia (CLL), 2 adult T cell leukemia (ATL), 1 acute lymphocytic leukemia (ALL), 8 breast cancer, 3 gastric cancer and 1 ovarian cancer. Twenty-three patients received either 3 million or 6 million units of HLBI by daily intramuscular injection or every other day. One patient with ATL received 18 million units of HLBI by i. v. daily and 1 patient with ALL received 30.32 million units of HLBI i. v. daily. Tumor regression (PR) was observed in 2 patients with MM, each one patient with ATL and ALL, respectively. Major toxicities were pyrexia, myelosuppression, general malaise and G.I. toxicity. Several patients showed abnormality of hepatic or renal function. Two patients who received HLBI for more than a year developed cardiac toxicity.
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PMID:[Clinical trial of human lymphoblastoid interferon on advanced malignancy]. 635 2

Preclinical as well as clinical studies with fibroblast interferon (IFN) are still lagging behind on those with leukocyte interferon. Its side-effects seem to be less pronounced than those of human IFN-alpha, yet it may be slightly pyrogenic after intravenous injection. Pyrogenicity of current impure preparations might for the larger part be due to impurities. Higher doses of HuIFN-beta than of HuIFN-alpha are required to obtain measurable blood titers by intramuscular injections. Since there is concern about this being due to destruction of the interferon before it has reached its target organ(s), most current clinical studies use either local (e.g. intratumoral) treatment or intravenous infusions. A study of topical treatment for acute rhinovirus infection has indicated that there is very little if any chance for fibroblast interferon to be a clinically useful substance to prevent or cure common cold. In herpetic dendritic keratitis eye drops of fibroblast interferon may be useful as such or in combination with debridement. Topical treatment of warts (multiple intralesional injections) has been shown to yield a high success rate, especially in the case of verrucae vulgares, but less so in the case of verrucae planae juveniles. Studies on condyloma accuminatum are not so far advanced as to permit a documented conclusion. Topical (intralesional) treatment of neoplastic diseases has been investigated, especially in Japan, to demonstrate that fibroblast interferon does have an antineoplastic effect in vivo. While there seems to be little doubt that local delivery does indeed cause tumor nodules to regress, the question is whether this procedure can offer a true clinical benefit to the patient. Systemic (intravenous) administration for chronic hepatitis B has been investigated further: given alone or in combination with adenine-arabinoside, fibroblast interferon seems to be able to reduce the level of viral activity. Whether this will lead to a generally accepted treatment of chronic active hepatitis is difficult to say at this moment. In treating herpes zoster in cancer patients, results have been obtained which are comparable to those found for leukocyte interferon. The practical significance of this finding must be seen in the perspective of recent developments in the chemotherapy of herpes zoster. In breast cancer patients given intramuscular injections, metastases in the skin, but not in other organs, showed alterations suggestive of an effect on tumor progression. Yet there was no true clinical benefit for the patient. In other tumors, e.g. head and neck epithelioma, no effect was seen.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The clinical application of fibroblast interferon--an overview. 640 34

The results of a randomised trial of polyadenylic-polyuridylic acid given as adjuvant treatment for operable breast cancer were reviewed after a mean follow up period of 87 months. Of the 300 patients included in the original trial, 145 had been allocated to conventional treatment alone and served as controls. At the time of review the overall survival of the group given polyadenylic-polyuridylic acid was significantly improved (p less than 0.05) as compared with that of the controls given conventional treatment alone. Significant benefit (p less than 0.02) was also observed among patients with evidence of disease in lymph nodes, the best results occurring in those with up to three invaded nodes, who showed a significant increase in both overall and relapse free survival. No evidence of toxicity was recorded. These findings confirm the value of polyadenylic-polyuridylic acid as adjuvant treatment for operable breast cancer. Results in an experimental model and in patients receiving the adjuvant suggested a possible role of interferon and natural killer (NK) cells in the mechanism of action.
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PMID:Adjuvant treatment with polyadenylic-polyuridylic acid in operable breast cancer: updated results of a randomised trial. 642 91

Thirty-three patients with advanced breast cancer were treated with a recombinant alpha interferon (rIFN-alpha 2). All patients were ambulatory (performance status greater than or equal to 50 Karnofsky scale) and almost all had received previous chemotherapy. Large intravenous dosages of 30 to 50 X 10(6) IU/m2 were given for five consecutive days every two to three weeks to 22 patients and smaller subcutaneous dosage of 2 X 10(6) IU/m2 three times a week to 11 patients. No complete or partial responses were seen. Two patients had stable disease and the remainder progressed. Flu-like syndromes were seen in all patients. Nausea, vomiting, and anorexia were frequent. Hypotension and confusion were noted in six and five patients, respectively. Life-threatening leukopenia was noted in two patients receiving intravenous dosage and thrombocytopenia was noted in one; no sepsis or bleeding complications were noted. In this study, a highly purified and biologically active rIFN-alpha 2 was not associated with activity in previously treated women with metastatic breast cancer.
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PMID:A phase II study of recombinant alpha interferon in patients with recurrent or metastatic breast cancer. 647 Jul 52

Fifty-two patients with advanced cancer received sequentially escalating doses of 3 to 50 million units of recombinant DNA-produced alpha interferon by daily intramuscular injection. There were 23 patients with metastatic breast cancer, 17 patients with nodular poorly differentiated lymphocytic lymphoma, and 12 patients with multiple myeloma. Complete and partial remissions were obtained in 35 percent of patients with nodular poorly differentiated lymphoma, whereas rare activity was found in breast cancer and multiple myeloma. Dose-limiting toxicity occurred in patients receiving 36 million units or more and consisted of fatigue/asthenia, weight loss, and elevation of transaminase levels, requiring frequent interruption, reduction in dose, or cessation of treatment. Hematologic toxicity was rarely a limiting factor, but myelosuppression was severe in some patients with multiple myeloma. All toxicities were reversible on discontinuation of treatment. Antibodies to recombinant leukocyte A interferon were seen infrequently but may adversely affect therapy.
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PMID:Collaborative phase I-II study of recombinant DNA-produced leukocyte interferon (clone A) in metastatic breast cancer, malignant lymphoma, and multiple myeloma. 654 79

Clonogenic tumor cells from fresh biopsies of human cancers were cultivated in vitro and tested for sensitivity by continuous exposure to pharmacologically achievable concentrations of either of two highly purified human leukocyte interferon subtypes (IFN-alpha A and IFN-alpha D) prepared by recombinant DNA methods. The interferons were compared on a weight basis at concentrations of 0.4 and 4.0 ng/ml (equivalent to 80 and 800 units of interferon activity for IFN-alpha A and 2.0 and 20 units for IFN-alpha D). Inhibition of tumor colony-forming units (50% of control or less) was observed in 38.1% of the 273 tumors tested against IFN-alpha A, and in 16% of the 71 tumors tested against IFN-alpha D. Of the tumor types with at least ten samples tested against IFN-alpha A, the percentage of cases exhibiting inhibition was as follows: melanoma (51.7%), lung cancer (50%), myeloma (33.4%), ovarian cancer (33.9%), sarcoma (33.3%), adenocarcinoma of unknown primary (30.4%), breast cancer (28%), acute leukemia (30.8%), and renal cancer (23%). More marked inhibition (30% of control or less) was observed in 18.7% of all tumors tested against IFN-alpha A. Of 60 melanomas tested, 18 (30%) exhibited marked in vitro inhibition of growth with IFN-alpha A. Although a smaller number of tumors (71) were tested against IFN-alpha D on a weight basis, it appeared, in general, to be slightly less active than IFN-alpha A (p less than 0.01), and only 8% of tumors tested exhibited marked inhibition over the same dosage range of interferon. Comparison of the dose-response curves for the 68 tumors tested simultaneously against both interferons did not reveal marked interpatient differences in the inhibition curves, although IFN-alpha D was slightly less active overall. Tumors exhibiting at least 50% inhibition of tumor colony formation also proved to be sensitive to a significantly larger number of cytotoxic drugs (tested simultaneously) than the tumors not inhibited with interferon (p less than 0.0001 for IFN-alpha A). We conclude that the in vitro clonogenic assay may aid in targeting tumor types most likely to exhibit interferon sensitivity and assist in case selection for entry into clinical trials with cloned interferons.
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PMID:Effects of cloned human leukocyte interferons in the human tumor stem cell assay. 668 47


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