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

The study of the relationship between dietary intake of vitamin E and the risk of breast cancer has not yielded definite conclusions with respect to causality, possibly due to methodological issues inherent to nutritional epidemiology. To avoid the pitfalls of dietary recalls, alpha-tocopherol content of adipose tissue was used as a biochemical indicator of long-term dietary intake of vitamin E. alpha-tocopherol and hydroperoxides were measured in breast adipose tissue obtained at the time of diagnosis from 70 patients with early breast cancer. Thirty women with non-malignant breast tumors served as control. Lipid peroxidation was monitored by quantifying conjugated dienes spectrophotometrically and by assaying hydroperoxides with an iodometric method; alpha-tocopherol was measured by HPLC associated with fluorescence detection. Mean alpha-tocopherol value in breast adipose tissue was significantly lower in breast cancer patients than in control patients, whereas the hydroperoxide content was significantly higher in cancer patients than in controls. The alpha-tocopherol concentration in adipose tissue was not correlated with the clinical status of the patients with respect to age, menopausal status or body mass index. We conclude from this pilot study that breast cancer is associated with a low content of alpha-tocopherol in breast adipose tissue, and with an altered lipid oxidation pattern, which might be related to a low antioxidant status.
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PMID:Alpha-tocopherol and hydroperoxide content in breast adipose tissue from patients with breast tumors. 876 May 82

The proliferation of MDA-MB-435 human breast cancer cells was inhibited by RRR-alpha-tocopheryl succinate (vitamin E succinate, VES). Conditioned media (CM) from VES growth-inhibited cells contained potent antiproliferative activity, part of which is contributed by transforming growth factor-beta (TGF-beta) isoforms. Antibody neutralization analysis, employing TGF-beta isoform-specific antibody reagents, showed that TGF-beta 1, -beta 2, and -beta 3 were present in the CM from VES-treated cells. Culturing MDA-MB-435 cells with VES did not alter the levels of constitutively expressed 2.4-kb TGF-beta 1, 3.0- and 4.0-kb TGF-beta 2, or 1.2- and 3.5-kb TGF-beta 3 mRNA transcripts. Inhibition of DNA synthesis by MDA-MB-435 cells was increased by combinations of suboptimal levels of VES and purified TGF-beta 1. VES-treated MDA-MB-435 cells exhibited enhanced binding of radiolabeled TGF-beta 1, and Western immunoblotting analyses showed that VES treatment enhanced TGF-beta type II receptor protein expression. TGF-beta type I receptor protein levels were not modified by VES treatments. Although the mRNA transcript for the 5.5-kb TGF-beta type II receptor was upregulated after four hours of treatment with VES, this treatment did not modify the 6.5-kb TGF-beta type I or the 6.5-kb TGF-beta type II receptor mRNAs. Results demonstrate that biologically active TGF-beta 1, -beta 2, -beta 3 and levels of TGF-beta type II receptor expressed by human breast cancer cells are enhanced by VES treatment.
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PMID:RRR-alpha-tocopheryl succinate enhances TGF-beta 1, -beta 2, and -beta 3 and TGF-beta R-II expression by human MDA-MB-435 breast cancer cells. 887 61

The effects of lipid peroxidation and the antioxidant vitamin E contained in LDL isolated from control plasma (LDL--) and from plasma preincubated with 0.5 mmol/ml alpha-tocopherol (LDL+) on the proliferation of estrogen-receptor positive (ER+ : ZR-75, T-47-D, MCF-7) and negative (ER--: HBL-100, MDA-MB-231) human breast cancer cells were studied. Human skin fibroblasts served as controls. Incubation of plasma with 0.5 mmol/ml alpha-tocopherol resulted in a 3-fold increase of its content and a significant reduction in lipid hydroperoxides and conjugated dienes in LDL. Incubation of fibroblasts or ER+ tumor cells with LDL- or LDL+ had an effect on neither cell proliferation nor on the cellular levels of peroxidation products as compared to control incubations in the absence of LDL. In ER- cells, however, LDL+ stimulated the proliferation, whereas LDL- yielded a cytotoxic effect. Moreover, LDL- supplementation resulted in an increase in the content of hydroperoxides and conjugated dienes. LDL+ supplemented cells exhibited hydroperoxide levels in these tumor cells comparable to the basal levels measured in the absence of LDL. Our data suggested that peroxidation products in LDL are cytotoxic to estrogen-receptor negative breast tumor cells and vitamin E counteracts this effect.
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PMID:Influence of LDL oxidation on the proliferation of human breast cancer cells. 890 87

Previous data on animals and humans suggest that vitamin E may be a protective factor against cancer. A low dietary vitamin E intake has been suggested to increase the risk of breast cancer. We examined the dietary intake and the concentration of vitamin E in breast adipose tissue of women in Kuopio, Finland, diagnosed between 1990 and 1992 with benign breast disease (n = 34) and with breast cancer (n = 32). In postmenopausal women, lower dietary intake (P = 0.006) and a smaller concentration of vitamin E in breast adipose tissue (P = 0.024) were observed in breast cancer patients than in subjects with benign breast disease. Partial correlation showed that the vitamin E concentration in the breast adipose tissue correlated positively with the dietary intake of vitamin E (r = 0.25, P = 0.023), indicating that the vitamin E concentration in breast adipose tissue reflects the dietary intake of vitamin E.
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PMID:Vitamin E concentration in breast adipose tissue of breast cancer patients (Kuopio, Finland). 893 19

Association between breast cancer risk and the intake of vitamins C and E, retinol, beta (beta)-carotene, dietary fibre, vegetables, fruit and potatoes was examined in The Netherlands Cohort Study, for 62,573 women aged 55-69 years. After 4.3 years of follow-up, 650 incident breast cancer cases were identified. After adjusting for traditional risk factors, breast cancer risk was not influenced by the intake of beta-carotene, vitamin E, dietary fibre, supplements with vitamin C, vegetables or potatoes. Fruit consumption showed a non-significant inverse association with breast cancer risk (RR highest/lowest quintile = 0.76, 95% CI 0.54-1.08). A small reduction in risk was also observed with increasing intake of dietary vitamin C (RR highest/lowest quintile = 0.77, 95% CI 0.55-1.08). For retinol, a weak positive association was observed (RR highest/lowest quintile = 1.24, 95% CI 0.83-1.83). Among subjects with a high intake of polyunsaturated fatty acids (PUFAs), both beta-carotene and vitamin C intake showed a non-significant inverse association with breast cancer risk (P-trend = 0.15 and 0.16 respectively). Our findings do not suggest a strong role, if any, for intake of vitamins C and E, beta-carotene, retinol, dietary fibre, vegetables, fruit and potatoes in the aetiology of breast cancer.
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PMID:Vitamins C and E, retinol, beta-carotene and dietary fibre in relation to breast cancer risk: a prospective cohort study. 900 Jun 14

Many anticipate that application of findings in molecular genetics will help to achieve greater precision in defining high-risk populations that may benefit from chemopreventive interventions. We must recognize, however, that genetic susceptibility, environmental factors, and complex gene-environment interactions are all likely to be risk determinants for most cancers. Cohort studies of twins and cancer indicate that having "identical" genes is generally not a very accurate predictor of cancer incidence. Data from twin studies support the suggestion that environmental factors such as tobacco use significantly influence cancer risk. The complexities of the genetic contribution to disease risk are exemplified by the development of Duchenne muscular dystrophy in only one of monozygotic twin girls, hypothesized to be the result of X chromosome inactivation, with the distribution patterns of the X chromosome being skewed to the female X in the manifesting twin and to the male X in the normal twin. Evidence from transgenic and genetic-environmental studies in animals support the possibility of genetic-environmental interactions. Calorie restriction modifies tumor expression in p53 knockout mice; a high-fat, low-calcium, low-vitamin D diet increases prepolyp hyperplasia formation in Apc-mutated mice; and calorie restriction early in life influences development of obesity in the genetically obese Zucker rat (fafa). Such environmental modulation of gene expression suggests that chemoprevention has the potential to reduce risk for both environmentally and genetically determined cancers. In view of the growing research efforts in chemoprevention, the NCI has developed a Prevention Trials Decision Network (PTDN) to formalize the evaluation and approval process for large-scale chemoprevention trials. The PTDN addresses large trial prioritization and the associated issues of minority recruitment and retention; identification and validation of biomarkers as intermediate endpoints for cancer; and chemopreventive agent selection and development. A comprehensive database is being established to support the PTDN's decision-making process and will help to determine which agents investigated in preclinical and early phase clinical trials should move to large-scale testing. Cohorts for large-scale chemoprevention trials include individuals who are determined to be at high risk as a result of genetic predisposition, carcinogenic exposure, or the presence of biomarkers indicative of increased risk. Current large-scale trials in well-defined, high-risk populations include the Breast Cancer Prevention Trial (tamoxifen), the Prostate Cancer Prevention Trial (finasteride), and the N-(4-hydroxyphenyl) retinamide (4-HPR) breast cancer prevention study being conducted in Milan. Biomarker studies will provide valuable information for refining the design and facilitating the implementation of future large-scale trials. For example, potential biomarkers are being assessed at biopsy in women with ductal carcinoma in situ (DCIS). The women are then randomized to either placebo, tamoxifen, 4-HPR, or tamoxifen plus 4-HPR for 2-4 weeks, at which time surgery is performed and the biomarkers reassessed to determine biomarker modulation by the interventions. For prostate cancer, modulation of prostatic intraepithelial neoplasia (PIN) by 4-HPR and difluoromethylornithine is being investigated; similar studies are being planned for oltipraz, dehydroepiandrosterone, and vitamin E plus selenomethionine. The validation of biomarkers as surrogate endpoints for cancer incidence in high-risk cohorts will allow more agents to be evaluated in shorter studies that use fewer subjects to achieve the desired statistical power.
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PMID:Cancer risk factors for selecting cohorts for large-scale chemoprevention trials. 902 95

Vitamin E succinate (VES), a derivative of the fat-soluble vitamin D-alpha-tocopherol (vitamin E), inhibited growth and induced apoptotic cell death of estrogen receptor-negative human breast cancer cells. VES-induced apoptosis in MDA-MB-231 and SKBR-3 cells occurred through a Fas pathway. Total protein levels of the Fas receptor (Fas; APO-1/CD-95) and the Fas ligand (Fas-L) were increased following VES treatment. In addition, VES increased cell surface Fas expression. Fas-neutralizing antibodies and Fas-L antisense oligonucleotides blocked VES-induced apoptosis. The presence of Fas-L antisense oligonucleotides also completely blocked the VES-mediated increase in Fas-L protein expression. These data indicate a role for Fas signaling in VES-mediated apoptotic cell death of human breast cancer cells. These findings also suggest that VES may be of clinical use in the treatment of aggressive human breast cancers, particularly those that are refractory to antiestrogen therapy.
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PMID:Vitamin E succinate induces Fas-mediated apoptosis in estrogen receptor-negative human breast cancer cells. 904 Nov 90

Tocotrienols are a form of vitamin E, having an unsaturated isoprenoid side-chain rather than the saturated side-chain of tocopherols. The tocotrienol-rich fraction (TRF) from palm oil contains alpha-tocopherol and a mixture of alpha-, gamma- and delta-tocotrienols. Earlier studies have shown that tocotrienols display anticancer activity. We previously reported that TRF, alpha-, gamma- and delta-tocotrienols inhibited proliferation of estrogen receptor-negative MDA-MB-435 human breast cancer cells with 50% inhibitory concentrations (IC50) of 180, 90, 30 and 90 microg/mL, respectively, whereas alpha-tocopherol had no effect at concentrations up to 500 microg/mL. Further experiments with estrogen receptor-positive MCF-7 cells showed that tocotrienols also inhibited their proliferation, as measured by [3H] thymidine incorporation. The IC50s for TRF, alpha-tocopherol, alpha-, gamma- and delta-tocotrienols were 4, 125, 6, 2 and 2 microg/mL, respectively. Tamoxifen, a widely used synthetic antiestrogen inhibits the growth of MCF-7 cells with an IC50 of 0.04 microg/mL. We tested 1:1 combinations of TRF, alpha-tocopherol and the individual tocotrienols with tamoxifen in both cell lines. In the MDA-MB-435 cells, all of the combinations were found to be synergistic. In the MCF-7 cells, only 1:1 combinations of gamma- or delta-tocotrienol with tamoxifen showed a synergistic inhibitory effect on the proliferative rate and growth of the cells. The inhibition by tocotrienols was not overcome by addition of excess estradiol to the medium. These results suggest that tocotrienols are effective inhibitors of both estrogen receptor-negative and -positive cells and that combinations with tamoxifen should be considered as a possible improvement in breast cancer therapy.
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PMID:Inhibition of proliferation of estrogen receptor-negative MDA-MB-435 and -positive MCF-7 human breast cancer cells by palm oil tocotrienols and tamoxifen, alone and in combination. 908 43

MDA-MB-435 human breast cancer cells treated with 10 micrograms/ml of RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) for one, two, three, and four days exhibit 9%, 19%, 51%, and 73% apoptotic cells, respectively. Likewise, cells cultured for one, two, and three days with conditioned media (CM) obtained from MDA-MB-435 cells treated with VES exhibit 10%, 36%, and 74% apoptosis, respectively. A quantitative luciferase-based assay showed CM from VES-treated cells collected at 24 and 48 hours after treatment initiation to contain 75 and 32 pg of active transforming growth factor-beta (TGF-beta), respectively, per 10(6) cells. Although purified TGF-beta 1 is not an effective apoptotic agent for MDA-MD-435 cells, cotreatment of the cells for three days with suboptimal levels of VES (2.5 and 5 micrograms/ml) + 10 ng/ml of purified TGF-beta 1 enhanced apoptosis by 66% and 68%, respectively. Interference of the TGF-beta-signaling pathway by transient transfection of MDA-MB-435 cells with antisense oligomers to TGF-beta type II receptor (TGF-beta R-II) blocked VES-induced apoptosis. Likewise, addition of neutralizing antibodies to TGF-beta 1 or to all three mammalian isoforms of TGF-beta (TGF-beta 1, -beta 2, -beta 3) blocked VES- and CM-induced apoptosis. Furthermore, inhibitors of TGF-beta conversion from an inactive latent form to a biologically active form inhibited VES-induced apoptosis. In summary, the ability to reduce apoptosis by blocking TGF-beta or the TGF-beta receptor-signaling pathway with antisense oligomers or ligand-neutralizing antibodies or prevention of activation of TGF-beta indicates a role for TGF-beta signaling in VES-induced apoptosis.
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PMID:Evidence for role of transforming growth factor-beta in RRR-alpha-tocopheryl succinate-induced apoptosis of human MDA-MB-435 breast cancer cells. 910 57

The associations between dietary antioxidant vitamins, dietary fiber, and selected foods and risk of breast cancer were studied in 4697 initially cancer-free women, aged 15 years or older. At baseline (1967-1972) the women were interviewed for total habitual diet over the preceding year. During a 25-year follow-up period 88 breast cancer cases were diagnosed. There was a significant inverse gradient between milk consumption and occurrence of breast cancer, whereas higher consumption of fried meat was associated with increased risk of breast cancer. No significant relationships were found between the intakes of vitamin E, vitamin C, beta-carotene, lycopene, lutein or dietary fiber and the occurrence of breast cancer.
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PMID:Diet and breast cancer risk in a cohort of Finnish women. 910 4


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