Raloxifene (Evista) for breast cancer prevention in postmenopausal women

Preliminary results from a new study, unpublished but reported in a press release from the National Cancer Institute and widely disseminated in the public press, suggest that raloxifene (Evista) might be a better choice than tamoxifen (Nolvadex, and others) for prevention of breast cancer in high-risk postmenopausal women.     

Risk of breast cancer after onset of type 2 diabetes: evidence of detection bias in postmenopausal women

OBJECTIVE

To examine the risk of breast cancer in pre- and postmenopausal women with type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS

This was a population-based retrospective cohort study. Cox regression, stratified by pre- (<55 years) and postmenopausal (≥55 years) status, was used to estimate hazard ratios (HRs) for breast cancer, during earlier (0–3 months) and later (3 months to 10 years) time windows after diabetes index date.

RESULTS

Compared with women without T2D, HRs for breast cancer were 0.95 (95% CI 0.48–1.86; P = 0.88) and 1.31 (0.92–1.86; P = 0.14) in pre- and postmenopausal women with T2D, respectively, in the early time window, and 0.92 (0.75–1.13; P = 0.45) and 1.00 (0.90–1.11; P = 0.93) in pre- and postmenopausal women with T2D, respectively, in the later time window.

CONCLUSIONS

We observed a trend toward an increased risk of breast cancer in postmenopausal women with T2D, but only in the time period immediately after diabetes index date.Previous epidemiologic research suggests a modestly elevated risk of breast cancer in women with type 2 diabetes (T2D), particularly after menopause (1). However, it is unclear whether this increased risk is related to a potential detection bias or increased mammography screening surrounding diabetes onset (2,3). Women with a new diagnosis of T2D may have the advantage of increased screening opportunities, which could transpire into more cases of breast cancer being diagnosed in this population. Therefore, we examined the risk of breast cancer in pre- and postmenopausal women with incident T2D, during earlier and later time windows after diabetes index date.     

Chemoprevention of breast cancer: tamoxifen, raloxifene, and beyond

Breast cancer is the most common cancer and the second most common cause of cancer death among women in the United States. While nonrandomized studies have reported that prophylactic mastectomy or oophorectomy can significantly reduce the risk of breast cancer, these approaches are unacceptable to the majority of women. Chemoprevention, which is defined as the prevention of cancer by pharmacological agents that inhibit or reverse the process of carcinogenesis, has thus increasingly become the focus of breast cancer prevention efforts. The first-generation selective estrogen receptor modulator (SERM) tamoxifen is the only US Food and Drug Administration- approved drug for breast cancer prevention and reduces the risk of breast cancer by as much as 50% in high-risk women. Raloxifene, a second-generation SERM, also has demonstrated efficacy for breast cancer prevention and is being compared with tamoxifen in a large randomized trial that has recently completed accrual. The aromatase inhibitors (AIs) decrease the incidence of contralateral breast cancer when used in the adjuvant setting and are being evaluated in ongoing primary prevention studies. In addition, a number of novel agents, including antiinflammatory drugs and retinoid derivatives, which appear to be of promise based on preclinical and epidemiological data, are under investigation. Several important challenges remain, including determination of the appropriate dose and duration of treatment when used in the primary prevention setting and development of new research models using surrogate end points for breast cancer incidence and mortality to permit more rapid clinical application of promising new agents.     

Effects of tamoxifen on testosterone metabolism in postmenopausal women with breast cancer

Testosterone is a known estrogen precursor especially in postmenopausal women. Tamoxifen, an anti-estrogen, is used in the treatment of women with breast cancer in whom metastatic disease has been demonstrated. The action of Tamoxifen is thought to be to occupy the intracellular estrogen receptor sites in target tissues and thus block the action of the biologically active estrogen, estradiol. Effects of Tamoxifen on the production and metabolism of hormones have been postulated. We studied the kinetics of testosterone metabolism by the constant infusion of 3H-testosterone in six postmenopausal women with breast cancer prior to and during Tamoxifen therapy. The Tamoxifen did not produce any significant change in the metabolic clearance rate, the plasma concentration or the calculated blood production rate of testosterone. The only significant alteration in the conversion ratio of testosterone to metabolites was the reduction (p less than 0.02) in conversion to 5 alpha-dihydrotestosterone. A significant reduction in the plasma concentrations (p less than 0.05) of dehydroepiandrosterone and of luteinizing hormone (p less than 0.02) was found. Other steroid and peptide hormones did not show any significant changes. We conclude that Tamoxifen therapy has very little effect on the kinetics of testosterone metabolism in postmenopausal women with metastatic breast cancer.     

Bone mineral density and bone turnover in postmenopausal women treated for breast cancer

Chemotherapy and endocrine treatments for breast cancer are believed to increase risk of osteoporosis by causing early menopause in premenopausal women and by further depleting estrogen levels in postmenopausal women. Multivariate analyses were used to evaluate the contributions of 7 predictors (age, body mass index [BMI], family history of osteoporosis, months since menopause, past use of chemotherapy, and current use of tamoxifen or aromatase inhibitors) in explaining variability in bone mineral density (BMD) at the hip and the spine and bone turnover in 249 postmenopausal women who are breast cancer survivors. This report was an analysis of baseline data from a federally funded (1 R01 NR07743-01A1) intervention study on osteoporosis prevention. Mean age of the women was 58.5 years, and average BMI was 26.7 kg/m; 98% were white. All had measurable bone loss, 167 had chemotherapy, 76 were on tamoxifen, and 21 were on aromatase inhibitors. Women with higher BMI had higher BMD at the hip (P < .001) and the spine (P = .004). Women on tamoxifen had lower measures of bone formation (Alkphase B) (P < .001), suggesting less bone turnover, and higher BMD at the hip (P = .035). There was a trend for women who had received chemotherapy to have lower BMD at the spine (P = .06). The implications of these findings are discussed in the article.     

Effect of raloxifene on serum triglycerides in postmenopausal women: influence of predisposing factors for hypertriglyceridemia

BACKGROUND: Estrogen increases serum triglyceride (TG) levels and induces hypertriglyceridemia in susceptible women. The effect of raloxifene (RLX), a selective estrogen-receptor modulator, on serum TG has not been studied in detail. OBJECTIVE: The purpose of this study was to examine the effect of RLX on serum TG levels in postmenopausal women with and without osteoporosis, including those with predisposing factors for hypertriglyceridemia. METHODS: Fasting serum TG levels were assessed over 36 months in 2738 osteoporotic postmenopausal women (mean age, 67 years) assigned to placebo or RLX (60 or 120 mg/d) in an osteoporosis treatment trial and over 24 months in 1318 postmenopausal women without osteoporosis (mean age, 54 years) assigned to placebo or RLX (60 or 150 mg/d) in 3 osteoporosis prevention trials. RESULTS: In the osteoporosis treatment trial, the median serum TG concentration decreased in all groups, but significantly more in the placebo group (placebo, -3.4%; RLX 60 mg/d, -1.4%; RLX 120 mg/d, -1.3%; P = 0.002). In the osteoporosis prevention trials, the percentage change in median serum TG concentration was not significantly different among treatments (P = 0.22). Among women with varying degrees of hypertriglyceridemia at baseline (>2.82, >3.39, and >4.51 mmol/L), the median serum TG level at the end of the study decreased from baseline in all groups, with no significant differences among treatments (P > or = 0.13). The effect of RLX on serum TG level was not influenced by age, smoking status, use of alcohol, or presence of diabetes (P > or = 0.10 for all interactions). Among women in the highest tertile of body mass index (>26.4 kg/m2), RLX increased serum TG levels significantly compared with placebo (placebo, -3%; RLX 60 mg/d, 6%: RLX 120 mg/d, 4%; P < 0.05); the absolute increase from baseline with RLX in this subgroup was 0.05 mmol/L (4.4 mg/dL). CONCLUSIONS: RLX did not increase serum TG in postmenopausal women overall or among women with elevated TG levels or evidence of diabetes at baseline. TG levels increased slightly but statistically significantly in women in the upper tertile of body mass index who were treated with RLX.     

Radiodermatitis prevention with sucralfate in breast cancer: fundamental and clinical studies

Background  

Acute radiodermatitis induced by radiotherapy may affect the quality of life and in some cases requires withholding treatment. The present study concerns the protective effect of a 1% sucralfate lotion. We propose joint fundamental and clinical points of view.     

Antiarrhythmic action of beta-blockers: potential mechanisms

Sympathetic nervous system overactivity has been linked to ventricular tachyarrhythmias and sudden death. It has been hypothesized that the extent and nature of the arrhythmogenic effect of sympathetic stimulation depends on the underlying myocardial substrate, the mechanism of the arrhythmia, and the integrated effects of sympathetic stimulation in the particular individual circumstance. Multiple direct and indirect mechanisms of adrenergic action on the heart may benefit from the known antiarrhythmic actions of beta-blocker therapy and other interventions that decrease sympathetic tone. The antiarrhythmic mechanism of beta-blockade (and possibly alpha-blockade) will depend on the specific mechanism of the individual arrhythmia and will differ for those arrhythmias caused by tachycardia and ischemia, those caused by reentry and promoted by decreased conduction velocity and shortened refractoriness, and those caused by early or delayed afterdepolarizations, usually in the context of prolonged action potential duration. Antagonism of cardiac adrenergic activity by beta-blockade in particular is the best-established drug therapy to prevent ventricular arrhythmias.     

Role of lipids, lipoproteins and vitamins in women with breast cancer

OBJECTIVES: Improper balance between the production of reactive oxygen metabolites (ROMs), and antioxidative defense system have been defined as oxidative stress in various pathologic conditions. Lipids, lipoproteins and antioxidative vitamins have been associated with the risk of breast cancer. The present case-control study was conducted to investigate the status of antioxidative vitamins (A, C and E), lipids (total cholesterol; TC and triglycerides; TG), lipoproteins (high-density lipoprotein cholesterol; HDL-C and low-density lipoprotein cholesterol; LDL-C) and retinol-binding protein (RBP) in breast cancer patients. The aim of the study was to find out oxidative stress in breast cancer. DESIGN AND METHODS: Plasma lipids, lipoproteins and vitamins were estimated in 54 untreated breast cancer patients of different clinical stages and in 42 age- and sex-matched controls. RESULTS: Plasma TC (p < 0.05), and LDL-C and TG (p < 0.01) were found to be significantly elevated among breast cancer patients as compared to the controls. On the other hand, plasma HDL-C concentration (p < 0.001) and vitamin C and E (p < 0.01) were observed significantly decreased in breast cancer patients than in the controls. The maximum changes in plasma TC, and vitamin C and E concentrations were observed in breast cancer patients with stage IV when compared with controls. CONCLUSION: The study suggests that higher levels of TC and TG may play important role in carcinogenesis. Furthermore, the elevated plasma LDL-C concentration, which is more susceptible to oxidation, may result in higher lipid peroxidation in breast cancer patients. However, decreased concentrations of HDL-C and vitamin C and E are not likely to be sufficient enough to counter higher ROMs production reported earlier in breast cancer patients that may cause oxidative stress leading to cellular and molecular damage thereby resulting in cell proliferation and malignant conversions.     

Cathepsin D in breast cancer: mechanisms and clinical applications, a 1999 overview

A short review of the literature first confirms the clinical value of cathepsin D as a prognostic marker in breast cancer, when using well standardized assays. We then summarize results of studies, mostly performed in our laboratory, aimed at understanding the effect of cathepsin D overexpression on metastasis and the molecular mechanisms involved. Cathepsin D-cDNA transfection increases tumor cell proliferation in vitro and the metastatic potential of 3Y1-Ad12 embryonic rat tumorigenic cells when injected in vivo into nude mice. The mechanism by which cathepsin D increases the incidence of clinical metastasis involves increased cell growth and decreased contact inhibition rather than escape of cancer cells through the basement membrane. Different mechanisms are considered to explain this mitogenic activity. Cathepsin D could act as a protease following its activation at an acidic pH, or as a ligand of different membrane receptors at a more neutral pH. In this case cathepsin D can displace IGFII from the mannose-6-phosphate/IGFII receptor to the IGFI receptor or activate another membrane receptor to be identified. The nature of the mechanisms involved in vivo may depend on the micro environment of the tumor cells. These studies should guide in the development of new therapies aimed at inhibiting the deleterious effect of overexpressed cathepsin D.     

Diabetes and lung cancer among postmenopausal women

OBJECTIVE

Epidemiological evidence of diabetes as a lung cancer risk factor is limited and conflicting. Therefore, we assessed associations among diabetes, diabetes therapy, and lung cancer risk in postmenopausal women participating in the Women’s Health Initiative (WHI) study.

RESEARCH DESIGN AND METHODS

Postmenopausal women (n = 145,765), ages 50–79 years, including 8,154 women with diabetes at study entry were followed for a mean of 11 years with 2,257 lung cancers diagnosed. Information on diabetes therapy was collected via two methods (self-reported information on treatment history collected on a questionnaire at baseline and a face-to-face review of current medication containers that participants brought to the baseline visit). Lung cancers were confirmed by central medical record and pathology report review. Cox proportional hazards regression models adjusted for lung cancer risk factors were used to estimate hazard ratios (HRs) (95% CI) for diagnosis of diabetes and treatment of disease as risk factors for lung cancer.

RESULTS

Compared with women without diabetes, women with self-reported treated diabetes had a significantly higher risk of lung cancer (HR 1.27 [95% CI 1.02–1.59]), with risks increasing for women with diabetes requiring insulin treatment (1.71 [1.15–2.53]). However, we did not observe a significant association between lung cancer risk and diabetes not treated with medication or with duration of diabetes.

CONCLUSIONS

Postmenopausal women with treated diabetes, especially those using insulin, have a significantly higher risk of lung cancer. The influence of diabetes severity and specific classes of therapy for diabetes on lung cancer risk require future study.The prevalence of diabetes has been rapidly growing worldwide and has become a major public health concern. Epidemiological studies have shown that diabetes is associated with increased risk of several types of cancer, notably liver, pancreatic, endometrial, and colorectal cancers (1).Lung cancer is the leading cause of cancer-related death globally and in the U.S. (2). Preclinical studies support a role for diabetes and/or hyperglycemia in lung cancer development and growth (3–8). However, epidemiological evidence on the association of diabetes with lung cancer is limited and conflicting (1). Whereas some studies have reported significant (9) or nonsignificant higher risks of lung cancer associated with diabetes (10–13), especially among women (12,13), others have reported an inverse association between diabetes and lung cancer (14–17). These inconsistent results could stem from a number of factors including small sample size, different study design, or potential misclassification of exposures or confounding.The primary barrier to a more clear understanding of the association has been the lack of prospective studies of sufficient size and duration. The Women’s Health Initiative (WHI) is well positioned to overcome this barrier: it is a large prospective cohort study of postmenopausal women in which detailed information on diabetes and potential risk factors was collected at baseline, with 2,257 lung cancer cases adjudicated by centrally trained physicians through September 2010. In this study, we assessed associations among diabetes, diabetes therapy, and lung cancer risk in women participating in the WHI.     

健康绝经后妇女应用盐酸雷洛昔芬1年后骨代谢生化指标的变化

目的:观察盐酸雷洛昔芬对健康的绝经后妇女骨代谢生化指标的影响。方法:选取来解放军总医院体检的健康的绝经后妇女68名,所有患者均签署知情同意书,随机分为盐酸雷洛昔芬组与安慰剂组,双盲给药1年,观察其血清C端交联肽(CTX)和骨钙素用药前、用药中及用药后的变化。结果:盐酸雷洛昔芬组用药后6个月CTX由原来的3445.0pmoL/L降至1627.0pmoL/L,用药后12个月CTX降至2875.0pmoL/L,而安慰剂组则分别由原来的3064.5降低到2496.0及升至4497.0pmoL/L。两组用药6个月及12个月后组间差异均有显著性意义(P<0.005)。骨钙素:盐酸雷洛昔芬组用药后6个月由原来的16.000μg/L降至12.400μg/L,用药后12个月降至12.350μg/L,而安慰剂组则由原来的12.000升至12.100μg/L及12.400μg/L。两组用药6个月及12个月后组间差异均有显著性意义(P<0.005)。结论:盐酸雷洛昔芬可降低健康的中国绝经后妇女骨转换率,抑制骨吸收,可预防骨质疏松。     

Nursing perspectives on fulvestrant for the treatment of postmenopausal women with metastatic breast cancer

Fulvestrant is an estrogen receptor antagonist indicated for the treatment of hormone receptor-positive metastatic breast cancer (MBC) in postmenopausal women with disease progression following antiestrogen therapy. Fulvestrant has a different mechanism of action than other hormonal therapies, including aromatase inhibitors and tamoxifen. In clinical trials of postmenopausal women with MBC, fulvestrant was effective and well tolerated compared to anastrozole after failure of tamoxifen. The monthly injection regimen of fulvestrant provides nurses with an additional opportunity to improve patient adherence to hormonal therapy, reinforce patient education, and monitor side effects. Several ongoing trials will elucidate the role of fulvestrant in the treatment of MBC. Issues that are being addressed in those trials include alternative doses and schedules, efficacy and safety in other patient populations, and the development of novel treatment combinations. This article provides oncology nurses with the knowledge needed to educate patients on the use of fulvestrant, to effectively administer this medication, and to prevent and manage potential side effects.