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)

Information regarding the relationship of menopausal hot flushes to menstrual, reproductive and clinical events were obtained from women participating in a case-control study of breast cancer risk. Naturally menopausal women who reported the occurrence of menopausal hot flushes were compared with those without such complaints in an attempt to identify factors that might predict the occurrence of menopausal symptoms. Two-thirds of the women reported such symptoms. The symptomatic and asymptomatic groups did not differ in body weight, suggesting that extraglandular estrogen production in obese women does not protect against occurrence of menopausal symptoms. Neither past medical nor reproductive history were predictive of the occurrence of hot flushes. Women with hot flushes more commonly reported the occurrence of menstrual cycle variability and of long menstrual cycles during the 5 years before menopause. Since perimenopausal cycle variability probably reflects the irregular maturation of residual ovarian follicles accompanied by elevated gonadotropin concentrations, symptomatic women may have earlier activation of the neuroendocrine mechanism that has been associated with both pulsatile gonadotropin release and the hot flush.
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PMID:The relationship of menopausal hot flushes to medical and reproductive experience. 722 76

In pre-clinical and limited clinical studies, high doses ( > or = 200 mg/day) of the triphenylethylene derivative toremifene showed activity in estrogen receptor (ER) negative and ER-unknown metastatic breast cancer after progression on tamoxifen, and a mechanism of action independent of hormone receptor binding was speculated. The CALGB conducted a Phase II trial (CALGB 8945) to test the efficacy of high dose toremifene in a population of patients who had hormone receptor-negative, metastatic breast cancer with limited prior chemotherapy exposure, good performance status, and measurable disease. Twenty eligible patients received toremifene at a dose of 400 mg/day orally for 8 weeks. Toxicity was minimal. Nausea was reported by 20% of the patients, lightheadedness by 20%, weight loss by 20%, and hot flashes by 15%. There was no grade 3-4 toxicity. No objective responses were observed, and 5 of 6 patients with stable disease at 8 weeks developed progressive disease at 11 to 33 weeks. High dose toremifene (400 mg/day) is well-tolerated but imparts no detectable activity in hormone receptor-negative, metastatic breast cancer.
Breast Cancer Res Treat 1995
PMID:High dose toremifene for estrogen and progesterone receptor negative metastatic breast cancer: a phase II trial of the Cancer and Leukemia Group B (CALGB). 757 4

The symptomatic postmenopausal woman with breast cancer presents the clinician with a difficult task with respect to hormone replacement therapy (HRT). All of the published meta-analyses have been consistent in showing that there is a slightly increased risk of developing breast cancer in those patients using postmenopausal estrogens for greater than 10 years. However, there have been no published placebo-controlled clinical trials on the effects of HRT in women with a history of breast cancer. Quality of life must be balanced against the theoretical risk of tumor promotion. Assessment of osteoporotic and cardiac risk factors (i.e., smoking, hypertension, family history, hyperlipidemia) should influence the decision. Valid alternatives to estrogen replacement include low-dose progesterones such as Bellergal or vitamin E for hot flashes, and biphosphonates, calcium, anabolic steroids, and calcitonin for osteoporosis.
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PMID:The management of menopausal symptoms in women with breast cancer. 761 Jun 43

To determine the optimal daily dose of a new antiestrogen, droloxifene, for the treatment of advanced breast cancer, we have conducted a multicenter, randomized, double blind trial. Postmenopausal women with advanced breast cancer, who could not benefit from loco regional therapy, with positive or unknown estrogen or progesterone receptors were entered in this study. Droloxifene was administered in a double blind randomized design, with daily dose of either 20 (group I), 40 (group II) or 100 mg (group III). None of the patients had received previous systemic antitumor therapy, with the exception of adjuvant chemotherapy terminated at least one year before the patient's recruitment. Patients with at least one measurable tumoral lesion were entered into the trial. Three hundred and sixty nine patients have been enrolled, 234 are fully evaluable for efficacy. Objective response rate (CR + PR) is 31.1, 44.6 and 41.9% for the groups I, II and III respectively (P = NS). Time to response has been short: in the three groups, 50% of the responses have been observed within the 2 first months of treatment. Time to disease progression is 6, 8.3 and 6 months respectively for the 20, 40 and 100 mg/day treatment group. Side effects have been moderate and not dose related. Hot flushes and gastro intestinal disorders have been observed most often. This promising new drug deserves further study and randomized comparison versus tamoxifen.
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PMID:[Treatment of advanced breast cancer in postmenopausal women with droloxifene: results of a double-blind phase II trial for dose determination]. 820 43

As more women are living longer, there is an increasing need for women to discuss hormone replacement therapy (HRT) with their physicians. This task is complicated by areas of scientific uncertainty and evolving data concerning the risks and benefits of HRT. Benefits of HRT that are supported by strong scientific evidence include relief from menopausal symptoms such as hot flashes, prevention of osteoporosis, cardioprotective effects, relief of urogenital atrophy, and decreased urinary incontinence. Benefits supported by observational evidence include improvement of emotional lability and depression, improved sense of well-being in patients with rheumatoid arthritis, increased dermal and total skin thickness, improved verbal memory skills, and decreased risk of colon cancer. Risks to consider include a possible increase in the incidence of breast cancer and an increase in endometrial cancer in women who have an intact uterus and do not receive a progestin. Women in various risk groups, such as those at risk for coronary artery disease, osteoporosis, or breast cancer, must consider the risk-to-benefit ratio for their own individual circumstances.
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PMID:Current concepts in postmenopausal hormone replacement therapy. 869 Nov 83

The purpose of this research was to describe current sexual functioning in women with breast cancer comparing women treated with chemotherapy or endocrine therapy to women treated without pharmacological manipulation. Sixty-seven women diagnosed with stage I, II, or III breast cancer responded to a two-part mailed questionnaire. The first part of the questionnaire asked about menopausal symptoms (weight changes, hot flashes, mood swings, and anxiety attacks) the women might currently be experiencing and about various symptoms that might be currently interfering with sexual functioning (vaginal dryness, decreased libido, dyspareunia, and difficulty achieving orgasm). The second part of the questionnaire was the Derogatis Sexual Functioning Inventory (DSFI) designed to measure current sexual functioning in ten areas. The women who participated in this study were primarily middle class, white, and married. Controlling for endocrine therapy, the 25 women treated with chemotherapy were 6.5 times more likely than women not treated with chemotherapy to report weight changes (p = 0.001), 3.6 times more likely to report hot flashes (p = 0.02), and 6.5 times more likely to report mood swings (p = 0.001). Additionally, still controlling for endocrine therapy, the women treated with chemotherapy were 5.7 times more likely than women not treated with chemotherapy to report vaginal dryness (p = 0.001), 3.0 times more likely to report decreased libido (p = 0.04), 5.5 times more likely to report dyspareunia (p = 0.003), and 7.1 times more likely to report difficulty achieving orgasm (p = 0.004). Controlling for chemotherapy, the 20 women treated with endocrine therapy did not experience either menopausal or sexual dysfunction symptoms significantly differently from women not treated with endocrine therapy. Controlling for endocrine therapy, there was a significant negative effect of chemotherapy on body image (p = 0.01), affects (p = 0.001), psychological symptoms (p = 0.001), and overall sexual functioning (p = 0.02). However, controlling for chemotherapy, there was no significant effect of endocrine therapy on any of the DSFI subscales. This study indicates that women who have received chemotherapy are especially susceptible to adverse changes in their current sexual functioning.
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PMID:Sexual functioning in women with breast cancer after treatment with adjuvant therapy. 876 89

Toremifene (Fareston) is a triphenylethylene derivative structurally similar to tamoxifen (Nolvadex) that was selected for development based on its in vitro activity against breast cancer and its lesser uterotrophic effect than tamoxifen in rat models. In phase I and II studies conducted in several countries, toremifene was well tolerated over a wide range of doses (10 to 680 mg/d). The major side effects were hot flashes, nausea, and vomiting. Toremifene's excretion half-life is 5 days. It produces a modest decline in serum levels of luteinizing hormone, follicle-stimulating hormone, and antithrombin III, as well as an increase in sex hormone-binding globulin levels. In studies in which toremifene was used as first-line therapy in patients with estrogen receptor (ER)-positive or ER-unknown tumors, response rates to doses of 40 to 60 mg/day ranged from 30% to 54%. In two larger studies of patients who had proved refractory to tamoxifen therapy, toremifene produced an objective response rate of 4% to 5%. When patients with stable disease were added to those with objective responses, 27% to 28% of patients were considered to derive clinical benefit from toremifene. The dose range chosen for further study was 40 to 60 mg/d.
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PMID:Phase I and II studies of toremifene. 916 2

Compliance with estrogen replacement therapy (ERT) following surgical menopause is poor. In women who have a family history of ovarian cancer, fear of the oncogenic potential of estrogen might affect compliance with ERT following oophorectomy. Compliance with ERT in such a select group of women has not been previously reported. The aim of the present study was to report on compliance with and side effects of ERT in women with a family history of ovarian cancer who underwent oophorectomy either prophylactically or for benign disease. Eighty women with a family history of ovarian cancer who underwent oophorectomy at Roswell Park Cancer Institute were followed for a median duration of 4.2 years (range, 5 months to 14 years). Of the 76 women who were given prescriptions for ERT, the rates of commencement and maintenance of ERT at 1, 2, and 5 years were calculated. Side effects related to the different modalities of ERT were recorded. Seventy-one of 76 women (93.4%) who were given prescriptions for ERT initiated treatment. The rate of commencement of ERT was higher in premenopausal than in postmenopausal women (98.3% versus 75%, respectively, P = 0.003). Except for one patient who developed breast cancer after the oophorectomy and was advised to stop estrogen, all patients said they continued to use ERT. The maintenance rates at 1, 2, and 5 years were 100% as per patients' history. The pharmacy records for ERT prescription refills were reviewed for 52 patients who were on ERT for more than 1 year. ERT compliance was confirmed in 42 patients (80.7%). Seven of 30 patients (23.3%) who retained their uterus developed irregular uterine bleeding and 4 underwent endometrial biopsies. The incidence of irregular uterine bleeding was significantly higher after continuous compared to cyclic estrogen and progestogen (37.6 and 7% respectively, P = 0.049). Four patients (5.6%) complained of hot flashes and were managed by changing the dose or formula of estrogen. Compliance with ERT among patients with a family history of ovarian cancer who underwent oophorectomy either prophylactically or for benign disease was excellent. The presence of the uterus and the incidence of irregular uterine bleeding did not affect patients' compliance with ERT.
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PMID:Estrogen replacement therapy following oophorectomy in women with a family history of ovarian cancer. 923 29

We concluded a randomized crossover trial comparing tamoxifen 40 mg daily with ovarian ablation for treatment of metastatic breast cancer in premenopausal women. Objective responses (complete response (CR) plus partial response (PR)) were observed in 5/20 patients treated initially with tamoxifen and in 3/19 patients initially treated with ovarian ablation (p = 0.69). Seven additional patients were stable (SD) on tamoxifen while five additional patients were stable after ovarian ablation, for CR + PR + SD rates of 12/20 (60%) for tamoxifen and 8/19 (42%) for ovarian ablation (p = 0.34). Median time to disease progression was 184 days for tamoxifen and 126 days for ovarian ablation (p = 0.40, logrank test, odds ratio for progression 0.71). Overall survival times were also similar: a median of 2.35 years for tamoxifen and 2.46 years for ovarian ablation (p = 0.98, logrank test, odds ratio for death 1.07). Side effects from tamoxifen included hot flashes and menstrual abnormalities. With one exception, these toxicities were not sufficient to require dose reduction. In this small study, tamoxifen was associated with similar response rates, response durations, and survival times to those observed with ovarian ablation.
Breast Cancer Res Treat 1997 Jul
PMID:A randomized crossover trial of tamoxifen versus ovarian ablation for metastatic breast cancer in premenopausal women: a report of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trial MA.1. 926

Toremifene is a chlorinated tamoxifen analogue that is indicated for the treatment of postmenopausal hormone-dependent breast cancer. It competes with estradiol for estrogen receptors and has growth-inhibitory effects on MCF-7 breast cancer cells. At concentrations < 10(-6) mol/L, this growth inhibition can be reversed by estradiol, but at higher concentrations toremifene is cytotoxic. In dimethylbenzanthracene (DMBA)-induced mammary cancer in rats, toremifene has been shown to decrease the number of new tumours and to inhibit the growth of existing tumours. Toremifene causes growth inhibition by suppressing mitosis and inducing apoptosis. The mechanism by which these events occur may involve the induction of transforming growth factor-beta 1 and inhibition of insulin-like growth factor-1 (mecasermin). Toremifene is primarily an antiestrogen, but it has some estrogen agonist properties in postmenopausal women. The latter are reflected by the fall in luteinising hormone and follicle-stimulating hormone levels and the rise in sex hormone-binding globulin levels that are associated with its use in most women. After estrogen priming, toremifene 68mg administered orally has been found to exert a similar antiestrogenic effect on the vaginal epithelium in postmenopausal women as tamoxifen 60mg. The half-life of toremifene in plasma is 5 days, and the drug is > 99% bound to plasma proteins. The main metabolites of toremifene are N-demethyl-toremifene and deaminohydroxy-toremifene. Altered liver, but not kidney, function affects the pharmacokinetics of toremifene. Toremifene 60mg daily is as effective as tamoxifen 20mg daily in the treatment of postmenopausal hormone-dependent breast cancer, producing a response in about 50% of patients. Soft tissue and visceral metastases respond better to toremifene than bone metastases. Most of the adverse effects of toremifene are related to its activity at estrogen receptors and include hot flashes, vaginal discharge and nausea. Although toremifene decreases antithrombin III levels slightly, the incidence of thromboembolic complications is low. Thus far, no carcinogenic effects have been noted in humans, and preclinical data are mostly reassuring. Toremifene has favourable effects on serum lipids, and thus has potential in preventing coronary heart disease. Although toremifene is somewhat more expensive to use than tamoxifen, toremifene is an effective and well tolerated alternative to tamoxifen in the treatment of postmenopausal women with hormone-dependent breast cancer. No formal pharmacoeconomic comparisons of toremifene and tamoxifen have yet been published. Toremifene is potentially safer than tamoxifen in relation to carcinogenic effects and effects on serum lipids.
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PMID:Toremifene in postmenopausal breast cancer. Efficacy, safety and cost. 934 56


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