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)

Letrozole is an orally competitive aromatase inhibitor. This double-blind, randomised, multicentre trial was carried out to evaluate the endocrine effects of two doses of letrozole, 0.5 mg versus 2.5 mg orally daily, in postmenopausal advanced breast cancer patients progressing after tamoxifen. The pharmacokinetics of letrozole was also assessed. 46 patients entered the trial, 22 on letrozole 0.5 mg and 24 on 2.5 mg. A significant suppression of oestrone and oestradiol levels was achieved by both letrozole doses. Neither letrozole dose induced any changes in cortisol and aldosterone production at rest or after Synacthen stimulation. Androstenedione, testosterone, 17 alpha-OH progesterone, triiodothyronine (T3) thyroxine, (T4) and thyroid-stimulating hormone (TSH) plasma levels did not show any significant changes. Sex hormone binding globulin (SHBG), follicle-stimulating hormone (FSH) and luteinising hormone (LH) levels increased significantly over time. Plasma letrozole concentrations increased until reaching steady-state values after 1 month at the dose of 0.5 mg and after 2 months at 2.5 mg. In conclusion, both letrozole doses suppressed oestrogen levels without affecting adrenal activity.
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PMID:Double-blind, randomised, multicentre endocrine trial comparing two letrozole doses, in postmenopausal breast cancer patients. 1044 61

The objectives of this retrospective case series were to determine the prevalence and timing of menstrual abnormalities in early-stage breast cancer patients undergoing adjuvant methotrexate or anthracycline-based chemotherapy and to more fully assess the possible mechanism of the amenorrhea reported after chemotherapy. One hundred forty-two premenopausal patients undergoing adjuvant chemotherapy were analyzed for patient age, breast cancer stage, type of chemotherapy, and menstrual abnormalities before, during, and after chemotherapy completion. A 24-month minimum follow-up after chemotherapy completion was available for all patients. One hundred nine of 142 patients were evaluable. Sixty-nine patients (46 node negative, 23 node positive) received methotrexate-based chemotherapy, 33 patients (3 node negative, 30 node positive) received anthracycline-based chemotherapy, and 7 patients received both treatments (all node positive). Amenorrhea occurred in about a third of patients during chemotherapy (methotrexate groups 31%, anthracycline group 33%), and a higher proportion were amenorrheic 1 year after chemotherapy was completed (methotrexate group 45%, anthracycline group 46%). Abnormalities were more likely to occur in older premenopausal patients (Chi square = 6.18, p < 0.05), although 28% of patients under age 35 developed persistent abnormal menses. In some amenorrheic patients, follicle-stimulating hormone (FSH) levels were decreased within 6 months of chemotherapy (24.4 IU). The levels tended to be higher after chemotherapy (59.1 IU), suggesting ovarian failure. Menstrual abnormalities and menopause will frequently occur in premenopausal early-stage breast cancer patients, with 30% of all patients amenorrheic 1 year after chemotherapy.
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PMID:The risk of premature menopause induced by chemotherapy for early breast cancer. 1053 97

Ovarian hormones are biomarkers for breast cancer risk. Soybean consumption may be responsible in part for lower levels of ovarian hormones and decreased rates of breast cancer in women in Asia compared with Western populations. Soybeans contain a significant amount of the isoflavones daidzein and genistein, which are weak estrogens. The purpose of this study was to determine whether soya feeding decreases circulating levels of ovarian hormones and gonadotropins. Ten healthy, regularly cycling women consumed a constant soya-containing diet on a metabolic unit, starting on day 2 of a menstrual cycle until day 2 of the next cycle. Blood and urine samples were obtained daily for one menstrual cycle before and during soy feeding. The diet was calculated to maintain constant body weight, included 400 kilocalories from a 36-ounce portion of soymilk, and provided 113-207 mg/day (154.0+/-8.4 mg/day, mean +/- SE) of total isoflavones. For the group, the soya diet provided more carbohydrate and less protein than the home diets. Daily consumption of the soya diet reduced circulating levels of 17beta-estradiol by 25% (P<0.01, Wilcoxon signed rank test, two-tailed) and of progesterone by 45% (P<0.0001) compared with levels during the home diet period but had no effect on luteinizing hormone or follicle-stimulating hormone. Mean menstrual cycle length did not change during the soya diet; a slight decrease in mean luteal cycle length was marginally statistically significant (P = 0.06). Urinary excretion of isoflavones was 33.8+/-5.3 mg/day (mean +/- SE) and when expressed as percentage of intake, varied substantially (21.9+/-3.3% of intake; range, 9.1-36.7%) among the subjects. Mean daily serum levels of daidzein and genistein (free and conjugated forms) 15 h after soymilk were 2.89+/-0.53 microg/ml and 0.85+/-0.22 microg/ml, respectively, indicating systemic bioavailability of these substances. Secondary analyses by multiple regression showed that decreases in follicular and luteal phase 17beta-estradiol levels were positively associated with urinary isoflavone excretion, an association affected by age, and were inversely associated with decreases in protein intake. Decreases in progesterone levels during the soya diet were inversely associated with increases in intakes of genistein and were affected by the interaction of the intakes of daidzein with energy or with fiber. Consumption of an isoflavone-containing soya diet reduced levels of ovarian steroids in normal women over the entire menstrual cycle without affecting gonadotropins. This suggests that at least under the conditions of this study, soya-induced reductions of circulating ovarian steroids are not mediated by gonadotropins. Decreases in ovarian hormones are related to isoflavones contained in soy and also to energy intake and other components such as protein and fiber but not fat. Our results may explain decreased ovarian hormone levels and decreased risk of breast cancer in populations consuming soya diets and have implications for reducing breast cancer risk by dietary intervention.
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PMID:Decreased ovarian hormones during a soya diet: implications for breast cancer prevention. 1094 18

In order to investigate the presence of established risk factors for endometrial carcinoma in postmenopausal patients with breast cancer and with tamoxifen-associated endometrial polyps we compared a group of 25 patients with tamoxifen-associated endometrial polyps with 25 tamoxifen-treated patients without endometrial polyps. No significant differences were found between both groups of patients in age, parity, time after breast cancer and after menopause, duration and daily and total cumulative dose of tamoxifen intake, body mass index and serum levels of luteinising hormone (LH), follicle-stimulating hormone (FSH), oestradiol (E2), progesterone, sex hormone-binding globulin (SHBG), tamoxifen and CA125. So far there is no evidence that these polyps are premalignant lesions.
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PMID:Absence of correlation between risk factors for endometrial cancer and the presence of tamoxifen-associated endometrial polyps in postmenopausal patients with breast cancer. 1105 12

Pulsatile gonadotropin-releasing hormone (GnRH) stimulates the pituitary secretion of both luteinising hormone (LH) and follicle-stimulating hormone (FSH) and thus controls the hormonal and reproductive function of the gonads. Blockade of GnRH effects may be wanted for a variety of reasons-eg, to prevent untimely luteinisation during assisted reproduction or in the treatment of sex-hormone-dependent disorders. Selective blockade of LH/FSH secretion and subsequent chemical castration have previously been achieved by desensitising the pituitary to continuously administered GnRH or by giving long-acting GnRH agonists. Only recently have GnRH-receptor antagonists, that immediately block GnRH's effects, been developed for clinical use with acceptable pharmacokinetic, safety, and commercial profiles. In assisted reproduction, these compounds seem to be as effective as established therapy but with shorter treatment times, less use of gonadotropic hormones, improved patient acceptance, and fewer follicles and oocytes. All current indications for GnRH-agonist desensitisation may prove to be indications for a GnRH antagonist, including endometriosis, leiomyoma, and breast cancer in women, benign prostatic hypertrophy and prostatic carcinoma in men, and central precocious puberty in children. However, the best clinical evidence so far has been in assisted reproduction and prostate cancer.
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PMID:Gonadotropin-releasing-hormone-receptor antagonists. 1173 58

Isoflavones, phytoestrogens contained in soy foods, may play a role in breast cancer prevention. This randomized double-blinded trial with 34 premenopausal women investigated whether 100 mg of isoflavones per day versus placebo affects the ovulatory cycle during 1 year. Compliance with the study regimen was confirmed by the increase of urinary isoflavone excretion among the intervention group. Blood samples were taken 5 days after ovulation as determined by an ovulation kit, at baseline, and at months 1, 3, 6, and 12. Serum levels of estrone, estradiol, estrone sulfate, progesterone, sex hormone-binding globulin, follicle-stimulating hormone, and luteinizing hormone were quantified by immunoassay; free estradiol was calculated. We applied the method of least squares to fit general linear models to test for an intervention effect while taking into account the repeated measurement design. Except for a small difference in age, the two groups were comparable at baseline. Menstrual cycle length did not change significantly during the intervention [F(1,32) = 0.69; P = 0.44]. During 1 year, we did not observe any significant changes in hormone levels by treatment group. The difference in change between intervention and control group was -13.0 pg/ml (95% confidence interval, -57.5 to 31.5) for estradiol and 6.9 pg/ml (95% confidence interval, -17.8 to 31.5) for estrone. Exclusion of 22 non-ovulatory cycles, noncompliant women, or non-Asian women did not affect the results. These findings do not support the hypothesis that isoflavones affect the ovulatory cycles of premenopausal women over a 1-year period. However, isoflavones alone may have different effects on the reproductive cycle than isoflavones present in soy foods.
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PMID:A randomized isoflavone intervention among premenopausal women. 1186 7

Cimicifuga racemosa (CR) is widely used in the treatment of menopausal symptoms. Mechanistic studies suggest that unlike hormone-replacement therapy, CR does not stimulate estrogen-receptor positive breast cancer cells. To evaluate CR safety, we performed an in vivo investigation of a clinically tested isopropanolic CR extract. Mammary tumors were induced in Sprague Dawley rats (n = 75) by the application of 7,12-dimethylbenz[a]anthracene. Five to nine weeks later, the animals were ovariectomized, allowed to recover, and administered daily doses of CR extract (0.714, 7.14, or 71.4 mg/kg body weight per day) or control substances (estrogen/positive control: 450 microg/kg/day mestranol; or CR vehicle/negative control). The animals were sacrificed 6 weeks later, and tumor number, size, plasma hormone levels, and the weight of estrogen-sensitive organs were analyzed. In contrast to mestranol treatment, CR treatment did not stimulate cancerous growth. There were no significant differences in tumor number or size between the CR groups and the vehicle control. Likewise, prolactin, follicle-stimulating hormone, and luteinizing hormone levels and organ weights and endometrial proliferation were unaffected. The lack of mammary tumor-stimulating effects of this extract is of great significance in establishing the safety of CR extracts for treatment of menopausal symptoms in women with a history of breast cancer in which hormone-replacement therapy is contraindicated.
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PMID:Lack of promotion of estrogen-dependent mammary gland tumors in vivo by an isopropanolic Cimicifuga racemosa extract. 1206 87

Possible advantages of the reduced estrogen does in the newer combined oral contraceptives (OCs) are assessed by means of retrospective study results and theoretical arguments. A complete analysis of the effects of lower estrogen doses would require double-blind prospective studies. The so-called third generation of progestins (desogestrel, gestodene, and norgestimate) have permitted estrogen doses to be greatly decreased. Some combined OCs now contain only 20 mcg of ethinyl estradiol, compared to 50 or more in the earliest formulations. No longterm studies exist that would allow the efficacy of pills with reduced estrogen doses to be compared to that of higher dose formulations. But data from applications for marketing authorization of the low dose formulations expressed in Pearl indices suggest that their efficacy is no lower than that of older formulations. Few studies have compared clinical tolerance of the low-dose OCs with those having higher estrogen doses. None of the existing studies indicate that clinical tolerance of the third generation OCs is less satisfactory and most suggest that it is similar. Lowering the dose of ethinyl estradiol has a beneficial effect on the ratio of total cholesterol to HDL cholesterol and a smaller but persistent effect on triglycerides. The diabetogenic effect is also lessened with lower estrogen doses. Modifications of hemostasis appear to depend on the ethinyl estradiol dose, and they are less marked with 20 mcg of ethinyl estradiol than with 50 mcg. The risks of venous and arterial accidents appear to be lessened with diminished estrogen doses. Only 2 studies have evaluated the risk of breast cancer as a function of estrogen dose, taking into account the duration of use and the various risk factors for breast cancer. The risk of breast cancer was lower in both studies for OCs with the lowest estrogen doses, but the results should be interpreted with caution. Sample sizes for greater durations of use were very small. 2 recent studies of luteinizing hormone and follicle-stimulating hormone levels among users of low-dose OCs contradict the theoretical argument that low-dose formulations will provide insufficient ovarian inhibition. In individual cases of apparently insufficient antigonadotropic effect, the prescription can be modified. The decrease in estrogen doses appears overall to entail more benefits than disadvantages.
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PMID:[Oral contraception: advantages of estrogen reduction]. 1231 39

Depot medroxyprogesterone acetate (DMPA, Depo-Provera) is used for contraception by 8-9 million women in more than 90 countries, including the US, as of January 1993. Pharmacologically active levels of DMPA persist for 3-4 months following injection. A 150 mg dose is used most often for high contraceptive efficacy every 3 months. Norethindrone enanthate (NET-EN, Noristerat) is somewhat less widely used and is not marketed in the US. Injectables act primarily by inhibiting ovulation, lowering the levels of follicle-stimulating hormone and luteinizing hormone. Approximately 50% of women using DMPA for 1 year report amenorrhea whose occurrence is less frequent with NET-EN. Menstrual changes are the most frequent causes of discontinuation of injectables. In cases of heavy bleeding it is appropriate to undergo gynecological examination to rule out unrelated conditions, such as vaginitis, cervicitis, or cervical lesions. The use of conjugated estrogen (12.5-2.5 mg daily) for 10-21 days will minimize bleeding. Some women using injectables experience headache, dizziness, bloating of the abdomen or breast, and mood changes. Long-term use of DMPA or NET-EN can often result in 1-3 kg weight gain. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives was launched in 1979 to examine cancer risks with the use of DMPA in Thailand, Mexico, and Kenya. The relative risk of breast cancer was 1.21, which was statistically not significant. In women diagnosed with breast cancer under age 35, short-term exposure to DMPA was associated with a slightly increased breast cancer risk, which, however, was not associated with duration of use. DMPA dramatically lowers the risk of endometrial cancer for at least eight years following discontinuation of its use. DMPA did not alter the risk of cervical cancer. Fertility returns in 70% of former users within 12 months; it is suitable for postpartum and lactating women, and provides other noncontraceptive benefits.
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PMID:Injectable contraception: the USA perspective. 1234 20

Hormone receptors in normal breast tissue were reported to be under the influence of cyclic variations of serum hormones during the menstrual cycle. The current study aimed to demonstrate a similar relationship between the phase of the menstrual cycle and hormone receptor status in operable, premenopausal patients with breast cancer. Patients were prospectively categorized according to the first day of last menstrual period into clinically defined follicular/luteal, perimenstrual/mid-cycle and unopposed estrogen/rest of the cycle phases and hormonally defined follicular/luteal phases. Serum follicle-stimulating hormone, luteinizing hormone, estrogen and progesterone levels were determined on the day of the operation. Estrogen and progesterone receptors in the tissues were detected by immunohistochemistry. Eighty-eight consecutive premenopausal patients with breast cancer were included in the study. Estrogen and progesterone receptors were positive in 57 (64.8%) and 40 (70.2%) patients respectively. Forty-nine patients were in follicular, and 39 patients in luteal phases according to serum hormone levels. Estrogen receptor positivity was significantly higher in hormonally defined follicular phase (p=0.025) and also had a tendency to be higher in perimenstrual phase (p=0.048). In contrast, progesterone receptor status was found to be independent of the phases of the menstrual cycle. As a conclusion, hormone receptor status might change during different phases of the menstrual cycle due to a possible effect of the circulating hormones and if it is found as negative, should he re-evaluated concerning the phase of the menstrual cycle in which the operation was performed.
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PMID:Menstrual cycle and hormone receptor status in breast cancer patients. 1238 29


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