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)

Raloxifene is the first Selective Estrogen Receptor Modulator (SERM) approved for the prevention and treatment of osteoporosis in postmenopausal women. Acting as an estrogen agonist in the skeleton and on lipid metabolism, raloxifene maintains bone mineral density (BMD) and prevents new vertebral fractures while improving the lipid profile in postmenopausal women. In an osteoporosis prevention study, 601 women without osteoporosis, aged 45 to 60 years, were assigned to receive a placebo or raloxifene 30, 60, or 150 mg/day. All women received calcium (400 to 600 mg/day). Raloxifene 60 mg increased BMD by 2.4% at both the lumbar spine and hip compared with the placebo at 36 months. More importantly, however, raloxifene significantly reduced the risk of new vertebral fractures in Multiple Outcomes of Raloxifene Evaluation (MORE), a placebo-controlled, double-blind randomized trial of 7705 postmenopausal women with osteoporosis. The women, with a mean age of 66.5 years, and with hip or spine T-score <-2.5 and/or prevalent vertebral fractures, were assigned to receive either a placebo or 60 mg or 120 mg of raloxifene. All women were provided supplemental calcium (500 mg/day) and vitamin D (400 IU/day). After 36 months, raloxifene 60 mg/day and 120 mg/day, reduced the risk of new vertebral fractures by 55% (RR 0.45, 95% CI 0.3, 0.7; p<0.001), and 40% (RR 0.60, CI 0.4, 0.9) in women without prevalent baseline fractures, respectively; and by 31% (RR 0.7, 95% CI 0.6, 0.9; p<0.001), and 49% (RR 0.5, CI 0.4, 0.6) in women with prevalent baseline fractures compared with the placebo. There was no difference in the proportion of women reporting non-traumatic, non - spine fractures among women receiving raloxifene compared to the placebo-treated women. Compared with placebo, BMD increased after 36 months by 2.1 and 2.6% at the femoral neck and spine, respectively, in the 60mg raloxifene group, and by 2.4 and 2.7% at the femoral neck and spine, respectively, in the 120mg raloxifene group. By 40 months of follow-up, there was a higher rate of deep venous thrombosis (38 cases) and pulmonary embolus (17 cases) in the combined raloxifene groups than in the placebo group (5 and 3 cases,), with a relative risk of 3.1, (CI 1.5-6.2). By 40 months, 54 women had a confirmed diagnosis of breast cancer with a relative risk compared to placebo of 0.35, (CI, 0.21-0.58). Raloxifene therapy for 3 years maintains BMD in healthy postmenopausal women and significantly reduces the risk of new vertebral fractures by about half in postmenopausal women with osteoporosis. Raloxifene also reduces the risk of breast cancer by 65% in postmenopausal women with osteoporosis thus providing a new choice for addressing postmenopausal health concerns.
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PMID:Raloxifene: results from the MORE study. 1575 5

Clinical trials show that hormone therapy (HT) is an effective treatment for vasomotor symptoms and vaginal dryness. HT improves other symptoms including sleep and quality of life in women who have menopause symptoms. In the Women's Health Initiative controlled clinical trials, both estrogen therapy (ET) and estrogen plus progestin therapy (EPT) reduced fracture risk, neither reduced the risk of heart disease, and both increased the risk of stroke, deep vein thrombosis, and dementia. EPT, but not ET, increased breast cancer risk and reduced colon cancer risk. Differences between EPT and ET may reflect chance, baseline differences between the EPT and ET cohorts, or a progestin effect. Studies of younger women and lower HT doses with intermediate endpoints are beginning.
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PMID:The rise and fall of menopausal hormone therapy. 1576 Feb 83

Toremifene has been in clinical use for 8 years for the treatment of advanced hormone-sensitive breast cancer and the adjuvant treatment of early breast cancer. More than 350,000 patient treatment years have accumulated, sufficient to allow evaluation of its longer-term safety profile in comparison with tamoxifen and, where possible, with raloxifene and aromatase inhibitors. We reviewed all preclinical and clinical safety data from 1978 to 2004 and comparative clinical safety data between October 1995 and the end of 2004. Secondary endometrial cancer incidence was lower with toremifene than with tamoxifen and was similar to that with raloxifene. It is speculated that toremifene may unmask existing endometrial tumors rather than induce new events. The risk of stroke, pulmonary embolism, and cataract may be lower with toremifene than with tamoxifen and the risk of pulmonary embolism and deep vein thrombosis lower than with raloxifene. Beneficial estrogen agonistic effects were equivalent to those of tamoxifen regarding bone mineral density and superior regarding lipid profiles.
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PMID:Toremifene: an evaluation of its safety profile. 1628 4

Estrogen therapy has been well established as an effective treatment for relief of vasomotor symptoms. In light of recent evidence from large randomized trials showing serious risks associated with use of estrogen treatment, current recommendations for hormone therapy emphasize using the lowest effective dose for the shortest possible time. The purpose of this review is to examine what has been learned from the Women's Health Initiative (WHI) Hormone Trials and other studies about the short-term risks and benefits of estrogen use. A second purpose is to examine whether short-term risks differ for women most likely to use hormone treatment, including individuals with vasomotor symptoms; women in their 50s; and women, with and without intact ovaries, who have had a hysterectomy. During the first 1 to 2 years of use of conjugated equine estrogens alone (E-alone) or combined with medroxyprogesterone acetate (E + P), women experience an elevated risk of coronary heart disease, stroke, and deep vein thrombosis or pulmonary embolism. The magnitude of risk is greater for E + P than for E-alone. Fracture risk is not reduced with 1 to 2 years of use, but a fracture benefit is seen within 5 years of use. Increased risk of breast cancer does not appear until after 4 to 5 years of E + P use and was not increased with E-alone use after < or =7 years of treatment. This pattern of risks and benefits is generally similar for women with vasomotor symptoms, women in their 50s, and women, with and without > or =1 intact ovary, who have had a hysterectomy.
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PMID:Estrogen with and without progestin: benefits and risks of short-term use. 1641 31

Policy makers have suggested that information about genetic risk factors, which are associated with low risk and for which preventive strategies exist, should not be considered "exceptional" and should not warrant special safeguards, such as data protection or specialist pre-test counselling. There is scant research on how such risk factors are perceived, and to explore this we conducted qualitative interviews with 42 participants who had undergone testing in the South West of England for a low risk genetic susceptibility to deep vein thrombosis (DVT). Generally the participants, who were mostly women, thought the test was less serious than a genetic test for a predisposition to breast cancer or a non-genetic, diagnostic test for diabetes. They had used the genetic information to reduce their risk of DVTs by avoiding oral contraceptives and hormone replacement therapy but had not changed their lifestyle. Many considered pre-test genetic counselling unnecessary. However, a subgroup of participants, who were often less educated or at a high risk, were distressed and/or confused about thrombophilia and thought pre-test counselling would have been helpful. The findings indicate an emerging interpretation of genetics not as revealing exceptional or "in depth" knowledge about one's health and identity but as occasionally relevant surface information, which participants use to make specific health decisions but not to transform their everyday lives. However, the views of the subgroup indicate that some participants interpret thrombophilia as serious and/or need special support.
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PMID:Are genetic tests exceptional? Lessons from a qualitative study on thrombophilia. 1675 45

Capecitabine is converted to 5-fluorouracil by thymidine phosphorylase, and mitomycin C is capable of upregulating the expression of thymidine phosphorylase suggesting a synergistic effect. Fifty-three patients (median age 62 years) with anthracycline- and taxane-resistant, metastatic breast cancer received mitomycin C 6 mg/m(2) on day 1, and capecitabine (Xeloda) 2,000 mg/m(2)/day from day 1 to day 14 with cycles repeated every 4 weeks. Overall, 77.4% had visceral metastases and 33 were pretreated with >/=3 chemotherapy lines. A median of 6 cycles were given (range 1-19) with a complete response observed in 2 patients (3.9%), partial response in 17 (33.3%) and stable disease in 19 (37.2%). Overall response rate was 37.2% (95% CI, 24.0-50.5%), with a median duration of 10.4 months. Median time to progression was 8.1 months and median survival was 17.4 months (1- and 2-year survival rates of 60 and 28%, respectively). Toxicity was mild. The most frequent grade 3/4 events were neutropenia (5.7% of patients), diarrhea (3.8%), and deep venous thrombosis (3.8%). Capecitabine plus mitomycin C may represent an effective and manageable treatment option for advanced breast cancer patients resistant to anthracyclines and taxanes. This approach provides an alternative for pretreated patients with advanced breast cancer.
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PMID:Capecitabine and mitomycin C is an effective combination for anthracycline- and taxane-resistant metastatic breast cancer. 1704

Several medications have proved effective in reducing the fracture risk in postmenopausal women with osteoporosis. The optimal duration of use of these medications remains to be established, however. Gains in bone mineral density (BMD) persisted throughout 10 years of treatment with alendronate or 7 years with risedronate. However, proof of long-term protection against fractures was obtained only for shorter treatment periods, 4 years with alendronate and 5 years with risedronate. The persistence of treatment effects after drug discontinuation varies across medications, and further studies are needed before this point can be incorporated into treatment decisions. With raloxifene, the BMD effect observed after 3 and 4 years persisted when the drug was given for 8 years, and the fracture risk reduction was similar after 4 years and after 3 years. The long-term safety profile also was similar, with a significant decrease in the incidence of invasive estrogen-receptor-positive breast cancer and a persistent increase in the risk of deep vein thrombosis. However, a sharp drop in BMD occurred upon raloxifene discontinuation. Thus, 4 years may be appropriate for anti-resorptive drug therapy. However, the optimal treatment duration should be determined on a case-by-case basis according to the results of regular fracture-risk evaluations.
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PMID:How long should patients take medications for postmenopausal osteoporosis? 1722 74

Recently, the use of hormone replacement therapy (HRT) at menopause has become a matter of debate. Its utility has been questioned after the publication of the results of the Women's Health Initiative (WHI) studies. This trial was divided in two arms of which the first examined the use of combined HRT (continuous estrogens plus progestins) and the second the use of estrogens alone in menopausal women. The first arm was terminated prematurely at 5.2 years because the number of cases of coronary heart disease (CHD), strokes, venous thromboembolic disease, and breast cancer were more in women receiving HRT than in women receiving placebo, if the nominal confidence intervals (CIs) were taken into account. However, in the same study the authors made clear that the adjusted CIs should be taken into account instead of the nominal ones. These latter ones caused the ending of the trial. Moreover, WHI was criticized for its conclusions as far as cardiovascular disease is concerned because of serious defects regarding design of the trial. If the adjusted CIs were taken into account then the increase in adverse events was significant only for deep vein thrombosis. The second arm demonstrated that the use of estrogens was not correlated to an increase of neither breast cancer incidence nor cardiovascular disease. A closer look at the results of the WHI trial reveals that the use of HRT for 5 years should not be considered deleterious for the appearance of breast cancer, cardiovascular diseases, strokes, and pulmonary embolisms. We suggest that HRT should be given early in menopause. The regimen should be individualized for each patient. More intense follow-up should be offered to women with a positive family history of breast cancer, diagnosed coronary disease, and to women with a predisposition to deep venous thrombosis.
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PMID:Pitfalls of the WHIs: Women's Health Initiative. 1730 58

In 1998, the concept of breast cancer prevention became a reality with the approval of tamoxifen to reduce the risk of developing breast cancer in women at increased risk for the disease. This approval was based on decades of research on selective estrogen receptor modulators providing an understanding of the role of the estrogen receptor in breast cell growth, and an appreciation of the carcinogenic process. Although results from the Breast Cancer Prevention Trial demonstrated a 49% reduction in breast cancer in women at increased risk, there were associated toxicities related to the estrogenic effects of tamoxifen; that is, deep vein thrombosis, pulmonary embolism, and endometrial cancer. In an effort to improve its benefit-risk profile, tamoxifen is now being compared with raloxifene, a selective estrogen receptor modulator approved for the treatment and prevention of osteoporosis. This equivalency prevention Study of Tamoxifen and Raloxifene completed accrual of 19 747 high-risk postmenopausal women in November 2004. Meanwhile, another class of estrogen-directed drugs, the aromatase inhibitors, have shown efficacy in breast cancer adjuvant trials, spawning a number of prevention trials that have recently been initiated. As with breast cancer the hormonal contribution to prostate carcinogenesis was the basis for the Prostate Cancer Prevention Trial which showed that finasteride, an androgen antagonist, reduces the incidence of prostate cancer compared to placebo.
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PMID:Hormonal interventions to prevent hormonal cancers: breast and prostate cancers. 1741 94

Patients with cancer have an increased risk of venous thromboembolism (VTE). To further define the demographics, comorbidities, and risk factors of VTE in these patients, we analyzed a prospective registry of 5,451 patients with ultrasound confirmed deep vein thrombosis (DVT) from 183 hospitals in the United States. Cancer was reported in 1,768 (39%), of whom 1,096 (62.0%) had active cancer. Of these, 599 (54.7%) were receiving chemotherapy, and 226 (20.6%) had metastases. Lung (18.5%), colorectal (11.8%), and breast cancer (9.0%) were among the most common cancer types. Cancer patients were younger (median age 66 years vs. 70 years; p < 0.0001), were more likely to be male (50.4% vs. 44.5%; p = 0.0005), and had a lower average body mass index (26.6 kg/m(2) vs. 28.9 kg/m(2); p < 0.0001). Cancer patients less often received VTE prophylaxis prior to development of DVT compared to those with no cancer (308 of 1,096, 28.2% vs. 1,196 of 3,444, 34.6%; p < 0.0001). For DVT therapy, low-molecular-weight heparin (LMWH) as monotherapy without warfarin (142 of 1,086, 13.1% vs. 300 of 3,429, 8.7%; p < 0.0001) and inferior vena caval filters (234 of 1,086, 21.5% vs. 473 of 3,429, 13.8%; p < 0.0001) were utilized more often in cancer patients than in DVT patients without cancer. Cancer patients with DVT and neurological disease were twice as likely to receive inferior vena caval filters than those with no cancer (odds ratio 2.17, p = 0.005). In conclusion, cancer patients who develop DVT receive prophylaxis less often and more often receive filters than patients with no cancer who develop DVT. Future studies should focus on ways to improve implementation of prophylaxis in cancer patients and to further define the indications, efficacy, and safety of inferior vena caval filters in this population.
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PMID:Venous thromboembolism in patients with active cancer. 1784 56


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