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

During the phase I study of maytansine at our institution, some activity was observed against breast carcinoma and melanoma. A phase II study was thus initiated to more thoroughly investigate the activity of this drug against these two tumors. In 33 evaluable patients with melanoma, no complete or partial responses were observed. Twenty-one evaluable patients with breast cancer were entered and only one response (partial) was seen. The toxicity was similar to that observed in the phase I study and consisted mainly of diarrhea, paresthesias, phlebitis, and flu-like symptoms. Myelosuppression was infrequent and was short-lived when it occurred.
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PMID:Results of a phase II study of maytansine in patients with breast carcinoma and melanoma. 37 3

Thirteen pretreated advanced breast cancer patients received a combination of alpha interferon 5 million IU every 2 days, subcutaneously, plus tamoxifen 10 mg 3 times daily, until disease progression. The objective response rate was 15.4%: 1 patient achieved a complete response, 1 a partial response and 11 demonstrated stable disease; half of the patients were receptor negative and/or pretreated with hormonotherapy. Durations of response were 16 and 26 months for the CR and PR patients respectively; median progression-free survival was 4 months (range 0-26). Toxicities were registered according to WHO criteria: 4 patients stopped the treatment with interferon because of severe flu-like symptoms, while in the others the combination was generally accepted with good tolerance.
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PMID:Tamoxifen and alpha interferon in advanced breast cancer. 181 22

The human breast cancer cell line ZR-75-1 possesses androgen, estrogen, progesterone, and glucocorticoid receptors, thus offering a good model to study the specific role of each class of steroids in the control of breast cancer growth. Although the stimulatory action of classical estrogens (E2 and estrone) is well known, we have found a potent mitogenic effect of the adrenal estrogen androst-5-ene-3 beta,17 beta-diol (delta 5-diol) at concentrations within the range of those found in the serum of adult women, thus suggesting that delta 5-diol might be the most important estrogen in women. Androgens, on the other hand, exert a potent inhibitory effect on basal ZR-75-1 cell growth and completely reverse the stimulatory effect of estrogens on the same parameter. The antiproliferative effect of androgens was completely prevented by the antiandrogen OH-FLU, thus suggesting an action mediated by the androgen receptor. Part of the effect of androgens can be explained by the marked inhibition of estrogen receptor binding and mRNA levels by androgens. The antiproliferative effect of androgens is additive to that exerted by antiestrogens. Progestins, on the other hand, exert a specific antiproliferative effect in the presence of estrogens, the effect of progestins being antagonized by the stimulatory action of insulin on cell growth. Medroxyprogesterone acetate (MPA), a compound frequently used in the treatment of breast cancer in women, exerts its main inhibitory action through an androgen receptor-mediated action, whereas its glucocorticoid-like activity could play an additional role at high concentrations. All four classes of steroids are present, to various extents, as lipophilic esters of long-chain fatty acids. It is of interest to mention that all steroids that inhibit ZR-75-1 breast cancer cell growth (androgens, progestins, and glucocorticoids) stimulate the secretion and mRNA levels of gross cystic disease fluid protein-15 (GCDFP-15), whereas estrogens have the opposite effects, thus suggesting that GCDFP-15 could well be a good marker for monitoring the response to androgens, progestins, and antiestrogens during the course of breast cancer therapy.
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PMID:Interactions between estrogens, androgens, progestins, and glucocorticoids in ZR-75-1 human breast cancer cells. 214 71

Since interferon alfa-2b (Intron A) is useful as a single agent, it is important to determine if interferon can be combined with standard chemotherapy to improve both response and survival in patients with cancer. Using clonogenic assays, interferon was tested alone and in combination with cyclophosphamide (Cytoxan) or melphalan (Alkeran) using several dose and exposure schedules to evaluate cytotoxicity. In vitro, continuous-exposure interferon produced optimal cell kill. Maximum enhancement of cytotoxicity occurred with cyclophosphamide or melphalan pretreatment (1 hour) and/or simultaneous interferon treatment. Based upon these data, a phase I-II study was designed to determine the tolerance of cancer patients to a fixed dose of cyclophosphamide (150 mg/m2 p.o. daily X 4 days [days 2 to 5]) combined with increasing doses of interferon. Interferon was administered subcutaneously on treatment cycle days 1 to 5, plus days 8, 10, 12, 15, 17, and 19 of the 21-day regimen. Three patients had partial responses: one breast cancer, one angiosarcoma, and one myeloma (mixed). All patients reported mild flu-like symptoms, fatigue, and anorexia. Leukopenia occurred in all patients; three required treatment interruption to allow recovery. Eight patients had a fall in hemoglobin (mean decrease 1.4 g/dL). The combination of cyclophosphamide and interferon was safe and deserves further trial in cancer treatment. However, using this combination schedule, interferon doses greater than or equal to 5 X 10(6) IU were poorly tolerated and compromised administration of full-dose cyclophosphamide.
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PMID:Interferon alfa-2b-cyclophosphamide combination studies: in vitro and phase I-II clinical results. 376 44

Two populations of human blood lymphocytes--one forming rosettes with sheep erythrocytes, the other non-rosetting--are cytolytic in vitro for several long term cultured tumour-derived cell lines. A particular breast cancer-derived target cell (MDA-157) is only killed by the non-rosetting effector. Rosetting cells from normal donors infected or immunized with influenza virus augment cytolytic activity on MDA-157 targets by non-rosetting effector cells. Similar augmenting activity can be induced by incubating the rosetting population with sources of immune (gamma), but not leucocyte (alpha) interferon in vitro. This augmentation of cytolytic activity does not require compatibility at the major histocompatibility locus between the augmenting and effector populations.
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PMID:Effects of activated T cells on natural killing. 617 23

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

Bone metastases are a common cause of morbidity in patients with breast cancer. In an open, phase II, non-comparative trial to investigate the effects of repeated infusions of pamidronate (Aredia) on pain, mobility, analgesic consumption, bone healing and bone metabolism, 69 patients with breast cancer and bone metastases received pamidronate 60 mg intravenously in 250 ml normal saline over 1 or 4 hours every 2 weeks for a total of 13 infusions, until either progressive disease or a serious adverse event. Improvement in pain score was seen in 33 of 54 evaluable patients (61%) as measured by a linear analogue pain scale, and in 28 of 56 evaluable patients (50%) as measured on a 6-point pain scale: 18 (30%) of 60 evaluable patients showed reduction in a 6-point analgesic score, while 28 patients (50%) showed some improvement in mobility, as assessed by a questionnaire. Sclerosis appeared in > 25% of bone lesions in 2 patients and in < 25% of bone lesions in 12 patients. Urinary calcium/creatinine ratios fell dramatically during therapy. One patient developed symptomatic hypocalcemia, 1 showed deterioration in pre-existing renal insufficiency. Fever occurred in 19% of patients, and less than 20% developed flu-like symptoms. We conclude that intravenous infusions of pamidronate at a dose of 60 mg every 2 weeks produces a marked reduction in pain in patients with extensive bone metastases from breast cancer.
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PMID:Role of pamidronate in the management of bone metastases from breast cancer: results of a non-comparative multicenter phase II trial. Aredia Multinational Cooperative Group. 753 92

The effect of progesterone (Pg), medroxyprogesterone acetate (MPA), estradiol (E2), dihydrotestosterone (DHT) and dexamethasone (DEXA) was studied on the in vitro growth rate of a progestin-dependent (PD), estrogen-sensitive mammary tumor line originated in an MPA-treated BALB/c mouse (C4-HD), and on its estrogen-resistant variant (C4-HDR). The specificity of hormone action was further investigated using the anti-hormones RU-486 and hydroxyflutamide (FLU). Cell growth was evaluated in epithelial and fibroblast-enriched cultures using 3H-thymidine and/or autoradiography and immunocytochemistry. The results indicate that cell growth is directly stimulated by MPA and Pg at concentrations ranging from 10(-11) to 10(-7) M. RU486 prevented MPA-induced stimulation in concentrations 10 to 100 fold lower than those of MPA. When used alone, it inhibited cell proliferation only in concentrations higher than 10(-11) M. At nM concentrations, neither DEXA nor DHT stimulated 3H-thymidine uptake except DEXA at 100 nM. MPA-induced stimulation was not reverted by micromolar concentrations of FLU. As for E2 (10(-7)-10(-9) M) it prevented MPA stimulation only in cultures of estrogen-sensitive tumors. Progesterone receptors (PR) (475 +/- 115 fmoles/10(5) cells, n = 5) and estrogen receptors (ER) (ND-115 fmoles/10(5) cells, n = 5) were detected only in epithelial-enriched cultures. Serum from 7 day-MPA-treated mice induced a significant increase of 3H-thymidine uptake; an increase was also obtained with serum from untreated ovariectomized animals to which 1 nM-100 nM concentrations of MPA had been added. The stimulatory effect of the exogenous MPA was much lower than that of the serum obtained from MPA-treated animals. It is concluded that MPA stimulates cell growth of primary cultures of MPA-induced PD tumors via PR. The results provide support for a direct effect of MPA which may be mediated or potentiated by serum factors.
Breast Cancer Res Treat 1995 Aug
PMID:Effect of medroxyprogesterone acetate (MPA) and serum factors on cell proliferation in primary cultures of an MPA-induced mammary adenocarcinoma. 764 39

The study objective was to evaluate the psychometric properties of a decisional conflict scale (DCS) that elicits: 1) health-care consumers' uncertainty in making a health-related decision; 2) the factors contributing to the uncertainty; and 3) health-care consumers' perceived effective decision making. The DCS was developed in response to the lack of instruments available to evaluate health-care-consumer decision aids and to tailor decision-supporting interventions to particular consumer needs. The scale was evaluated with 909 individuals deciding about influenza immunization or breast cancer screening. A subsample of respondents was retested two weeks later. The test-retest reliability coefficient was 0.81. Internal consistency coefficients ranged from 0.78 to 0.92. The DCS discriminated significantly (p < 0.0002) between those who had strong intentions either to accept or to decline invitations to receive influenza vaccine or breast cancer screening and those whose intentions were uncertain. The scale also discriminated significantly (p < 0.0002) between those who accepted or rejected immunization and those who delayed their decisions to be immunized. There was a weak inverse correlation (r = -0.16, p < 0.05) between the DCS and knowledge test scores. The psychometric properties of the scale are acceptable. It is feasible and easy to administer. Evaluations of responsiveness to change and validation with more difficult decisions are warranted.
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PMID:Validation of a decisional conflict scale. 789 94

The escape of tumor cells from immune recognition is a central problem in tumor immunology. Here, we examined the functional role of somatic beta 2-microglobulin (beta2m) gene mutations in human lung and breast cancers. Using single-strand conformational polymorphism (SSCP) analysis and DNA sequencing, we found mutations in the beta2m gene in 2 of 110 tested lung, colon and breast tumors and tumor cell lines. No mutations were identified in 63 breast cancer tumors, in B-lymphoblastoid cell lines or normal tissues from these or other patients. In these cell lines, beta2m protein was undetectable by Western blot analysis and there was no MHC class I on their cell surface even after treatment with interferon-gamma. Transfection of these tumor cell lines with the beta2m gene, but not addition of purified beta2m protein restored MHC expression without addition of exogenous pepticles, indicating that endogenous beta2m expression is necessary for proper intracellular MHC assembly and stabilization by endogeneous pepticles. Mutation in beta2m caused cell line H2009 to be resistant to specific lysis by influenza virus-specific CTL from HLA matched donors, and transfection of the beta2m gene restored this killing. A small cell lung cancer cell line with low class I expression and with a normal beta2m genomic sequence nonetheless also demonstrated increased class I expression after transfection of the beta2m expression vector alone, indicating that the availability of beta2m may be rate limiting for MHC assembly in this line. Our results indicate that somatic mutations or selective loss of expression of the beta2m gene in human lung cancer is rare, but can cause defective MHC class I expression and function allowing these cells to escape recognition by cytotoxic T cells.
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PMID:Structural and functional analysis of beta2 microglobulin abnormalities in human lung and breast cancer. 882 45


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