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

The role of hormonal therapy for the treatment of patients with early stage breast cancer has been evaluated in many studies. The results of these studies establish tamoxifen as the gold standard of hormonal therapy for the adjuvant treatment of hormone receptor-positive invasive breast cancer in pre- and postmenopausal women. Studies show tamoxifen reduces the risk of invasive breast cancer in women at increased risk for the disease, including women with ductal carcinoma in situ. Tamoxifen has adverse effects such as hot flashes, increased risk of uterine cancer in postmenopausal women, and rare occurrence of thromboembolic disease. Despite the multiple therapeutic roles of tamoxifen, alternatives are needed. Aromatase inhibitors (AI) are drugs with antiestrogenic activity. AIs function by inhibiting the peripheral conversion of adrenally synthesized androstenedione to estradiol through inhibition of the aromatase enzyme. AIs do not suppress estradiol synthesis by the ovary adequately. Therefore, AIs are effective in reducing circulating estradiol levels in postmenopausal women, but not premenopausal women. Selective nonsteroidal AIs, including anastrozole (Arimidex; AstraZeneca, Wilmington, DE) and letrozole (Femara; Novartis, East Hanover, NJ), and the steroidal AI exemestane (Aromasin; Pharmacia, Peapack, NJ) have been associated with increased specificity and improved therapeutic index compared to nonselective AIs such as aminoglutethamide. Nonsteroidal and steroidal AIs have demonstrated to be superior to megestrol acetate in second-line therapy of postmenopausal women with metastatic breast cancer, and selective nonsteroidal AIs have shown to be superior to tamoxifen in first-line therapy of postmenopausal women with metastatic breast cancer. The ATAC (Arimidex, tamoxifen, alone, or in combination) trial is the only published randomized trial comparing the efficacy of an AI to tamoxifen for the adjuvant treatment of women with early breast cancer. This large study showed that at a median follow-up time of 33 months, anastrozole alone results in significant improvement in disease-free survival rates, reduction in contralateral breast cancers, and increased tolerability, compared to tamoxifen in postmenopausal women. Although the long-term effects of AIs are not known, the early positive results of the ATAC trial led to the approval of anastrozole by the US Food and Drug Administration for use as adjuvant hormonal therapy for postmenopausal women with hormone receptor-positive invasive breast cancer. Thus, there is an alternative to tamoxifen for postmenopausal women with relative/absolute contraindications to tamoxifen use or patients who choose not to take tamoxifen because of its side-effect profile. New AIs may challenge the position of tamoxifen as the gold standard for the treatment of early stage breast cancer in postmenopausal women.
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PMID:The role of aromatase inhibitors in early breast cancer. 1259 39

Products for hormone replacement therapy (HRT) in the postmenopause are the second most frequently prescribed drugs in the USA. Among the women receiving this treatment many are smokers. In the Women's Health Initiative (WHI), one of the largest interventional studies on HRT to date and which recently had to be discontinued, 50% of the 8,500 women on HRT had smoked before or continued to smoke during the study. Remarkably, there is little knowledge about the impact smoking has on the efficacy and side effects of HRT. However, it has been proven that, depending on the type, duration and intensity of nicotine consumption, smoking can reduce or completely cancel the efficacy of orally administered estrogens. Not only does smoking diminish the otherwise well-established beneficial effects of estrogen on hot flashes and urogenital symptoms and its positive effects on lipid metabolism, i.e. by reducing cholesterol, but smoking also specifically reduces estrogen's ability to prevent osteoporosis. The reduction or loss of therapeutic efficacy is mainly caused by dose-dependently elevated hepatic clearance, partially in conjunction with lower estrogen levels, and has been demonstrated only with oral estrogen applications. This failure of therapeutic action should not be compensated for by increasing the dose in smokers as this might result in the production of toxic, even potentially mutagenic estrogen metabolites-compounds recently associated with a higher risk of breast cancer. The favorable effects of estrogens are not lost in smokers when they are applied transdermally. This route enables low dosage and also avoids the formation of unphysiological metabolites by bypassing the liver. Women who continue to smoke despite all warnings should therefore only be treated via the transdermal route. Oral contraceptives, but not HRT, are contraindicated in elderly smokers. However, the principal conclusion of the WHI study was that the lowest dose possible should be chosen, especially in patients with an increased cardiovascular risk, as is the case in smokers.
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PMID:Smoking, estradiol metabolism and hormone replacement therapy. 1260 8

Selective estrogen receptor modulators (SERMs) are a class of compounds used to treat and prevent breast cancer and osteoporosis. SERMs currently approved for use in patients include tamoxifen, toremifene and raloxifene. These compounds are well tolerated in patients, and the most common adverse effects experienced in patients undergoing SERM therapy include vasomotor symptoms such as hot flashes and vaginal discharge. New SERMs currently under development for use in the treatment and prevention of osteoporosis and breast cancer include ospemifene, a derivative of toremifene, and arzoxifene, a compound very similar in structure to raloxifene. SERMs are administered orally at doses ranging from 20 to 60 mg/day. Tamoxifen and toremifene have a bioavailability of approximately 100%, whereas that of raloxifene is only 2%. SERMs are very highly bound to plasma proteins (>95%). Tamoxifen and toremifene are metabolised by the cytochrome p450 enzyme system, and raloxifene is metabolised by glucuronide conjugation. The terminal elimination half-lives of these drugs range from 27.7 hours to 7 days. The pharmacokinetics of these compounds are affected in hepatically impaired patients, but not in renally impaired patients. SERMs have several potential drug interactions with other agents, such as warfarin, rifampicin (rifampin), cholestyramine and aromatase inhibitors.
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PMID:Pharmacokinetics of selective estrogen receptor modulators. 1264 26

The primary objective of this study was to observe the effect of hypnosis on hot flashes (HF) and overall quality of life in symptomatic patients. A secondary objective was to observe the effect of hypnosis on fatigue. Ten healthy volunteers and four breast cancer patients (total 14 patients) with symptoms of HF were treated with four, 1 h/wk sessions of hypnosis. The same physician, with the help of a nurse, conducted every session. All subjects recorded frequency, duration, and severity of HF in a HF diary. The QLQ-C30 and Brief Fatigue Inventory forms were used to assess the impact on quality of life and fatigue, respectively. The statistical evaluations were performed, including analysis of variance and nonparametric procedures. The frequency (p < 0.0001), duration (p < 0.0001), and severity (p < 0.0001) of HF were significantly reduced. The overall quality of life was also improved (p = 0.05). The subjects enjoyed better sleep and had less insomnia (p = 0.012). There was a significant improvement on current fatigue level (p = 0.017), but we did not find a statistically significant reduction in the total fatigue level. We conclude that hypnosis appears to be a feasible and promising intervention for HF, with a potential to improve quality of life and insomnia. Although improvement in current level of fatigue was observed in this pilot study, total fatigue improvement did not reach statistical significance.
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PMID:Mind control of menopause. 1273 44

Phytoestrogens are weak estrogens found concentrated in soybeans. Americans consume phytoestrogens primarily in traditional soy foods, soymilk and isolated soy protein added during food processing or consumed as a beverage. Extracted phytoestrogens are also marketed in numerous forms as dietary supplements regulated under the Dietary Supplement Health and Education Act. Consumers of phytoestrogen supplements tend to be peri- and postmenopausal women looking for an alternative to hormone therapy. Although there are no approved health claims for phytoestrogens at this time, numerous claims are being made regarding benefits to heart, bone, breast and general menopausal health. The data supporting these claims are generally not strong. The strongest data show that phytoestrogens reduce the number and intensity of hot flashes, although the reduction is a modest 10-20%. The studies showing cholesterol lowering have used soy protein rather than phytoestrogen extracts. The soy protein appears to be required for this effect, although phytoestrogen extracts may have other beneficial effects on the cardiovascular system. The data on bone metabolism are suggestive of possible benefits whereas the effects on the breast are the most poorly understood. Although most animal studies have shown cancer-preventive effects, a few recent studies suggest that soy phytoestrogens may stimulate breast cancer cell growth under certain circumstances. Before recommendations regarding phytoestrogen supplements can be safely made, we must have more information on the effects of the extracts on bone, heart and breast health. Until safety with respect to breast cancer is established, phytoestrogen supplements should not be recommended, particularly for women at high risk of breast cancer.
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PMID:Phytoestrogen supplement use by women. 1277 50

Published literature indicates that the selective estrogen-receptor modulators (SERMs) tamoxifen and raloxifene (Evista) have favorable effects on bone density, lipid profiles, and the incidence of second breast cancers, and unfavorable effects on the incidence of venous thrombosis and hot flushes. Tamoxifen increases the risk of endometrial cancer, but raloxifene does not. The effects of SERMs on sexual function and cognition are unclear. Because the selective antiaromatase agents are relatively new, the long-term effects of these agents on normal tissues are less well established. It appears that the nonsteroidal agents (anastrozole [Arimidex], letrozole [Femara]) and steroidal (exemestane [Aromasin]) antiaromatase agents may have different effects on normal tissues. Preliminary data demonstrate that anastrozole increases the risk of arthralgias and produces a decrease in bone density. In contrast, exemestane appears to favorably affect bone density and lipid profile, similar to tamoxifen and raloxifene. The incidence of contralateral breast cancer is decreased in women on adjuvant anastrozole, but data for the other antiaromatase agents are not yet available. Hot flushes have been reported with the use of selective aromatase inhibitors, but their incidence seems to be comparable to what is reported with SERMs. Antiaromatase agents do not appear to cause venous thrombosis. More information about the effects of the antiaromatase agents on normal tissue will become available as data from ongoing adjuvant and chemoprevention trials are reported. Clinically, we should be conscious of the differences between antiaromatase agents and SERMs and their impact on women's health.
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PMID:Long-term toxicities of selective estrogen-receptor modulators and antiaromatase agents. 1280 Jul 93

We present an initial survival analysis and an update of the safety data of the North American and Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability (TARGET) double-blind, randomised, multicentre studies which compared anastrozole with tamoxifen as first-line treatment in postmenopausal patients with oestrogen receptor and/or progesterone receptor-positive (ER+/PR+) or receptor-unknown advanced breast cancer (ABC). At a median follow-up of 43.7 months, 56.0% of patients in the anastrozole group and 56.1% of patients in the tamoxifen group had died. The proportion of patients dead at 2 years was 31.1 and 32.0% in the anastrozole and tamoxifen groups, respectively. In the ER+/PR+ subgroup, 55.1 and 55.9% of patients had died and median time to deaths (TTD) were 40.8 and 41.3 months in the anastrozole and tamoxifen groups, respectively. Both agents remained well tolerated, with fewer reports of vaginal bleeding (anastrozole versus tamoxifen, 1.0% versus 2.5%) and thromboembolic events (anastrozole versus tamoxifen, 5.3% versus 9.0%) in the anastrozole group versus the tamoxifen group. Hot flushes and vaginal dryness were reported marginally less in the tamoxifen group compared with the Anastrozole group. Although no improvement in survival was observed, the favourable profile of anastrozole with respect to efficacy (TTP) and tolerability [Cancer 92 (2001) 2247] support the use of anastrozole in advance of tamoxifen as the first-line therapy choice in postmenopausal women with ABC.
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PMID:Anastrozole (Arimidex) versus tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: survival analysis and updated safety results. 1509 87

With the development of highly effective, well-tolerated third-generation aromatase inhibitors (AIs), these drugs will probably play an increasingly important role in all phases of breast cancer treatment. As a result, the impact of such hormonal agents on patients' quality of life bears rigorous investigation. In a randomized, multicenter, single-blind cross-over study, the AIs letrozole and anastrozole were evaluated for quality of life, toxicity, and patient preference. A total of 72 patients were enrolled and were treated with each drug for a 4-week period, with a 1-week drug-free washout period before cross-over to the alternate agent. Assessments included the FACT-ES, toxicity, and patient preference. The FACT-ES is a validated questionnaire designed to measure quality of life of women with breast cancer who are being treated with endocrine therapies. Letrozole was superior to anastrozole with respect to both quality of life and toxicity evaluations. In addition, at the conclusion of the trial, reduced nausea, hot flashes, and abdominal discomfort caused almost twice as many patients to prefer to continue with letrozole therapy than with anastrozole. Data from this recent trial indicate that letrozole is better tolerated and provides better quality of life than anastrozole for women with metastatic breast cancer.
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PMID:Examining quality of life issues in relation to endocrine therapy for breast cancer. 1290 76

Tamoxifen is useful for adjuvant treatment of breast cancer and in some women for the prevention of breast cancer. The risk-benefit ratio in regard to the skeleton and perhaps other organ systems may very well be different for postmenopausal versus premenopausal women. In postmenopausal women, tamoxifen (20 mg/d) increased BMD in the spine and perhaps the hip; however, the effect on fracture risk is unclear. Therefore, for postmenopausal women with osteoporosis, consideration should be given to the addition of an agent that is shown to have efficacy against fractures (such as bisphosphonates), even while these women are on tamoxifen. For women at only modest or moderate risk, with bone density above the osteoporosis range (T score above -2.5) and no major fracture history, tamoxifen is probably adequate for 5 years of use. Potentially serious adverse effects include venous thromboembolism, uterine cancer, benign uterine disease, and cataracts. Raloxifene (60 mg/d) protects against vertebral fractures over 4 years in women with osteoporosis, produces small increases in bone mass of the spine, hip, and total body, and reduces bone turnover in postmenopausal women with or without osteoporosis. No significant effect has yet been demonstrated on nonvertebral fractures after 4 years of treatment. Raloxifene has the additional benefit of substantially reducing the risk of ER-positive invasive breast cancer and does not increase the risk of uterine disease. Raloxifene increases the risk of venous thromboembolic disease to the same degree as tamoxifen and estrogen. Therefore, SERMS and estrogens are generally contraindicated in women with a previous history of venous thromboembolism or those who are at significantly increased risk. Raloxifene is probably most useful in women who have osteoporosis (T score = -2.5) or who are at risk (T score less than -1.5 with clinical risk factors) in the middle menopausal period (age 55-65) or in the early menopausal period in women who have no significant hot flashes. At this stage in life, vertebral fractures are common, but hip fractures are not. Therefore, women who take raloxifene can expect a reduction in the likelihood of having a vertebral fracture, and possibly breast cancer. The lack of definitive efficacy against hip fracture is not a major deterrent to use of this agent in this age group because hip fracture risk is very low. Raloxifene might not be the treatment of choice for elderly women who are at particularly high risk of hip fracture.
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PMID:Selective estrogen-receptor modulators. 1291 92

Hot flashes can be a major problem for patients with a history of breast cancer. The precipitation of menopause in premenopausal women who undergo chemotherapy for breast cancer can lead to the rapid onset of hot flash symptoms that are more frequent and more severe than those associated with natural menopause. In addition, tamoxifen, historically the most commonly prescribed pharmacologic agent for the treatment of breast cancer, is associated with hot flashes in more than 50% of its users. Although estrogen relieves hot flashes in 80-90% of women who initiate treatment, its use in women with a history of breast cancer is controversial, and most physicians in the community will not use this treatment modality. In addition, the results of the long-awaited Women's Health Initiative study and other recent studies suggest that long-term estrogen therapy should not be recommended for most women for a variety of reasons. However, hot flashes in breast cancer survivors should no longer be considered untreatable, as there are many pharmacologic and nonpharmacologic treatments that can help alleviate this problem. This article reviews the current strategies for the management of hot flashes in breast cancer survivors and the evidence supporting their use.
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PMID:Hot flashes in breast cancer survivors. 1296 72


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