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)

After primary surgery, 149 premenopausal breast cancer patients, with node-negative disease, were randomized to one of four treatment groups: goserelin, tamoxifen, goserelin plus tamoxifen or to a systematically untreated control group. The aim was to assess the effects of adjuvant endocrine therapy in terms of physical symptoms and perception of anxiety and depressive symptoms. Assessments were made before randomization, at 3-4 months and at 12 months. Treatment with goserelin resulted in early and more intense menopausal symptoms, while the effects of tamoxifen were slower and milder. The side effects with goserelin appeared to be alleviated by concurrent tamoxifen except for vasomotor symptoms (hot flashes, sweating, feeling warm). No significant group differences were found for anxiety and depressive symptoms. In conclusion, chemical castration with goserelin was associated with the highest level of physical symptoms. The group treated with tamoxifen alone showed the lowest levels of symptoms among the treatment groups, except for vaginal discharge and irregular bleedings.
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PMID:Randomized trial of adjuvant tamoxifen and/or goserelin in premenopausal breast cancer--self-rated physiological effects and symptoms. 1120 3

Estrogen replacement therapy either with (HRT) or without (ERT) accompanying progesterone is routinely offered to well women at the time of menopause, in order to relieve vasomotor symptoms, (hot flashes), reduce urogenital atrophy and reduce the risks of cardiovascular disease, osteoporosis and perhaps colon cancer and Alzheimer's disease. It is generally felt however, that women with a previous diagnosis of breast cancer are not suitable candidates for such therapy since either estrogen or progesterone may be associated with an increased risk of cancer recurrence. There are however, a variety of approaches to menopausal therapy in such women. A careful history must first be taken in order to identify the symptoms or conditions of concern. Vasomotor symptoms can be reduced by the use of other medications such as the antidepressant venlafaxine (Effexor). Estring, a vaginal estrogen ring can be used to reduce genitourinary symptoms, with little systemic estrogen absorption. Osteoporosis can be prevented or treated with calcium supplements, exercise, improved diet, bisphosphonates and/or selective estrogen receptor modulators (SERMs) while cardiovascular risk can be reduced by diet and exercise, as well as the appropriate use of lipid lowering and antihypertensive medications.
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PMID:The role of hormone replacement therapy in women with a previous diagnosis of breast cancer and a review of possible alternatives. 1133 40

Tamoxifen, a selective estrogen receptor modulator (SERM), is the treatment of choice for all stages of hormone-responsive breast cancer and has been shown to prevent breast cancer in high-risk women. Despite acting as an antiestrogen on the breast, tamoxifen has partial estrogenic effects on other target tissues. These partial estrogen agonistic actions produce beneficial effects on bones and the lipid profile in postmenopausal women. However, tamoxifen is associated with an increase in endometrial cancer. Additionally, its antiestrogenic effects in the central nervous system result in hot flashes in postmenopausal women. Raloxifene is another SERM approved for the prevention of osteoporosis in postmenopausal women. Like tamoxifen, raloxifene appears to prevent breast cancer in high-risk women and has not, to date, been noted to increase the incidence of endometrial cancer. The Study of Tamoxifen and Raloxifene will compare the effects of the two agents on breast cancer prevention and endometrial cancer risk. A number of new agents are being developed for breast cancer treatment and prevention and osteoporosis prevention. These include other SERMs, selective estrogen receptor downregulators (SERDs), and aromatase inhibitors. It is hoped that one of these new agents will be the ideal agent, acting as an antiestrogen on breast and endometrium while having estrogenic effects on bones, the lipid profile, and the central nervous system. Semin Oncol 28:260-273.
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PMID:Tamoxifen to raloxifene and beyond. 1140 36

Menopausal symptoms are important concerns for breast cancer survivors, which may influence daily activities, physical comfort and sexual health. Incidence and severity ratings of menopausal symptoms contribute to our knowledge about menopause in women with cancer, but fail to fully describe the symptom experience. The purpose of this article is to broaden our understanding by describing variation in menopausal symptom distress and how women interpret and manage symptoms within the context of breast cancer. From a larger grounded theory study that explored women's responses to the experience of premature induced menopause within the context of breast cancer, the constant comparative method of analysis was used to generate a detailed contextually grounded description of the menopausal symptom experience in a sample of 27 women with breast cancer who received adjuvant therapy. Women identified a symptom profile of menstrual cycle changes, hot flashes, insomnia, vaginal dryness, dyspareunia, alterations in mood, cognition and libido, and weight gain. The majority of women reported menopausal symptoms but some women were distress free while others reported moderate to severe distress. The context of breast cancer influenced women's response to symptoms and their decision making about menopausal symptom management.
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PMID:The menopausal symptom experience in young mid-life women with breast cancer. 1140 64

Female hormones, especially estrogens, play an important role in the pathogenesis of breast neoplasms and are a principal determinant of their biological behavior. Endocrine manipulation through medical or surgical means can often lead to objective shrinkage of breast tumors. Tamoxifen, a triphenylethylene estrogen receptor modulator, is currently the most widely used hormonal treatment for breast cancer. It has been conclusively demonstrated to reduce the risk of relapse following definitive local therapy (and systemic chemotherapy, when indicated) of invasive or noninvasive breast cancer. Recently, it has also been shown to reduce the incidence of breast cancer in healthy women who are at high risk of developing the disease. In addition, it can prevent osteoporosis and reduce the risk of fractures in postmenopausal women. However, its use is also complicated by an increased incidence of endometrial hyperplasia/carcinoma, venous thromboembolism, cataracts, and in some cases, emergence of tamoxifen-dependent clones of breast cancer. These side effects (except cataracts) are believed to be related to estrogen-agonist effects of tamoxifen. Newer drugs, which are "pure antiestrogens" or inhibitors of estrogen biosynthesis, are devoid of such estrogen-agonist activity and may not have the liability of many of these side effects. However, these agents would also be expected to lack the potentially beneficial effects of tamoxifen on lipids and skeletal system. The ability of tamoxifen to act as an estrogen-agonist or estrogen-antagonist in a tissue-specific fashion has led to the concept of selective estrogen-receptor modulation. Selective estrogen receptor modulators (SERMs), which are devoid of estrogen-agonist effects on the uterus or breast cancer cells but retain potentially beneficial effects on bones and lipids, have been described as "ideal" SERMs. A number of such compounds are currently being tested. Raloxifene is already approved for prevention of osteoporosis and has potential efficacy for prevention and treatment of breast cancer. An analogue of raloxifene, LY353381, is currently in Phase II clinical trials for treatment of breast cancer, with promising early results. EM800 and CP336156 are other promising ideal SERMs in clinical trials. These compounds may provide better treatment and chemoprevention alternatives for breast cancer as compared to tamoxifen, aromatase inhibitors, and pure antiestrogens. In addition, they may also prove to be useful for the treatment and prevention of prostate cancer as well as for treating benign gynecological diseases such as fibroids and endometriosis. Future laboratory efforts should focus on further broadening the efficacy profile of SERMs (e.g., prevention of Alzheimer's disease and elevation of high-density lipoproteins to improve the likelihood of cardiovascular benefit) and narrowing their side-effect profile (e.g., risk of thromboembolism and hot flashes).
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PMID:Selective estrogen receptor modulation: the search for an ideal hormonal therapy for breast cancer. 1148 8

Estrogen used alone (estrogen replacement therapy [ERT]) or with the addition of progesterone (hormone replacement therapy [HRT]) is known to be effective in reducing menopausal symptoms including hot flashes, vaginal dryness and urinary symptoms. It has been traditionally contraindicated, however, in women with a previous diagnosis of breast cancer because of fear that it may increase the risk of recurrence. There are considerable basic scientific data but little methodologically strong observational data and none from randomized studies concerning the use of ERT in women with a prior diagnosis of breast cancer. From our knowledge of the physiology of breast cancer, however, estrogen and/or progestational agents should be used with caution in women with a previous diagnosis of breast cancer. There are currently many alternatives to ERT/HRT in the prevention of menopausal symptoms such as vitamin E, clonidine and selective serotonin reuptake inhibitor antidepressants such as venlafaxine. There are also a variety of other approaches to the prevention of osteoporosis and cardiovascular disease including bisphosphonates, diet, and exercise; and diet, exercise, and statins, respectively. Other suggested beneficial effects of estrogen such as colon cancer prevention can be approached by the use of aspirin or the non-steroidals. Several trials of ERT/HRT used for 2 years versus no therapy in menopausal women with a previous diagnosis of breast cancer are ongoing in Europe and Britain, and should give us stronger data as to the role of HRT in this setting.
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PMID:Hormone replacement in women with a history of breast cancer. 1152 54

Menopause, an event often accompanied by symptoms such as hot flashes, can have a significant impact on a woman's quality of life. A majority of women will experience hot flashes at some point in their life, given a normal life span. Despite multiple theories, the exact pathophysiology of hot flashes is not yet known. Many types of treatment options exist for women with hot flashes, from hormonal and nonhormonal pharmacological therapies to nonpharmacological interventions. Choosing the best treatment option for specific women involves knowledge of the risks and benefits of each treatment. Hormones (estrogen and/or progesterone, or tibolone alone) are still the most effective option available, resulting in an 80 to 90% reduction in hot flashes. The best nonhormonal treatment to date is in the class of newer antidepressants that comprises various selective reuptake inhibitors; for example, venlafaxine provides about a 60% reduction in hot flashes. This article provides evidence-based information about available treatment options for hot flash management, with special consideration of populations such as breast cancer survivors.
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PMID:Hot flashes: aetiology and management. 1158 46

Tamoxifen (Nolvadex), a selective estrogen-receptor modulator, or SERM, is currently the endocrine therapy of choice for all stages of hormone-responsive breast cancer. Only tamoxifen has been approved by the US Food and Drug Administration to reduce the incidence of breast cancer in high-risk women. Despite tamoxifen's antiestrogenic effects in breast tissue, it exhibits paradoxical estrogenic effects in other tissues in the body. These effects result in the maintenance of bone mineral density, but a three- to fourfold increase in endometrial cancer in postmenopausal women. Additionally, tamoxifen can result in troublesome hot flashes and serious thromboembolic events. For this reason, current research is focusing on new agents that may maintain the beneficial effects of tamoxifen while reducing its adverse effects. Raloxifene (Evista) is another SERM, approved for the prevention of osteoporosis in postmenopausal women and now being compared with tamoxifen in an ongoing breast cancer prevention trial. Like tamoxifen, raloxifene is associated with hot flashes and thromboembolic events, but its association with the risk of endometrial cancer is unknown. A number of new SERMs are in preclinical or clinical development in an attempt to improve upon the safety profile of tamoxifen. Additionally, selective aromatase inhibitors are being examined in the early breast cancer setting.
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PMID:Selective estrogen-receptor modulators in 2001. 1158 65

To assess the psychometric properties of the Hot Flash Related Daily Interference Scale (HFRDIS), a sample of breast cancer survivors and an age-matched comparison group completed a questionnaire packet and 2-day prospective hot flash diary at an initial time point and again 6 months later. There were 71 breast cancer survivors and 63 comparators at Time 1, and 54 survivors and 46 comparators at Time 2. The HFRDIS was internally consistent, with alphas of 0.96 at times 1 and 2. Validity was supported through 1) correlations with other hot flash variables, 2) correlations with measures of affect and mood, 3) significant differences between women with hot flashes and those without, and 4) demonstrated sensitivity to change over time. The HFRDIS is a psychometrically sound measure for assessing the impact of hot flashes on daily activities and overall quality of life in clinical practice or research protocols.
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PMID:The Hot Flash Related Daily Interference Scale: a tool for assessing the impact of hot flashes on quality of life following breast cancer. 1173 60

This article reviews the symptoms and everyday problems associated with tamoxifen adjuvant therapy and their impact on patients' quality of life. In addition, the purported toxic effects of tamoxifen therapy (e.g., premature menopause, weight gain, and depression) are discussed, and data are presented that refute claims of the toxicity of tamoxifen therapy. From randomized controlled trials of adjuvant therapy, we know that tamoxifen therapy increases the rate of hot flashes, night sweats, and vaginal discharge; however, in observational studies these symptoms do not have a statistically significant impact on patients' quality of life as measured by standardized, self-report questionnaires. The Breast Cancer Prevention Trial found no evidence of excessive rates of depression or clinically significant differences in sexual functioning between women receiving placebo and those receiving tamoxifen therapy. Although several serious medical risks from tamoxifen therapy exist (e.g., uterine cancer, blood clots, stroke, and cataracts), there are additional benefits from tamoxifen therapy in addition to an increase in disease-free survival rates and overall survival rates, including a decrease in contralateral breast cancer and fractures. Ultimately, the decision to receive tamoxifen therapy is a personal choice for each woman to make on the basis of the evidence of tamoxifen therapy's benefits and risks, along with her own motivation to receive therapy. When the benefits of such therapy are small, some women may choose to avoid treatment, but others may wish to try therapy to determine whether possible side effects are relevant. For women in whom the absolute survival benefits are large, there may be less difficulty in making this decision.
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PMID:Impact of tamoxifen adjuvant therapy on symptoms, functioning, and quality of life. 1177 6


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