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The standard therapy for hot flashes has been hormone replacement (HRT) with estradiol or progestational agents. Recent studies suggest that serotin reuptake inhibitors may also be effective. The authors set [...]

Objectives: To evaluate the relationships among measures of hot flushes, perceived hot flush interference, sleep disturbance, and measures of quality of life while controlling for potential covariates (patient and treatment variables).Methods: Breast cancer survivors (n = 395) due to receive aromatase inhibitor therapy provided demographic information, physiological hot flush data via sternal skin conductance monitoring, hot flush frequency via written diary and electronic event marker, hot flush severity and bother via written diary, and questionnaire data via the Hot Flash Related Daily Interference Scale, Pittsburgh Sleep Quality Index, the EuroQOL, Hospital Anxiety and Depression Scale and the Center for Epidemiologic Studies Depression Scale.Results: Confirmatory factor analysis supported a two-factor model for hot flush symptoms (frequency and severity). Although there was strong convergence among self-reported hot flush measures, there was a high degree of unexplained variance associated with physiological measures. This suggests that self-report and physiological measures do not overlap substantially. The structural model showed that greater hot flush frequency and severity were directly related to greater perceived interference with daily life activities. Greater perceived interference, in turn, directly predicted greater sleep disruption, which predicted lower perceived health state and more symptoms of anxiety and depression.Conclusions: Findings suggest hot flush interference may be the most appropriate single measure to include in clinical trials of vasomotor symptom therapies. Measuring and ameliorating patients' perceptions of hot flush interference with life activities and subjective sleep quality may be the most direct routes to improving quality of life. [ABSTRACT FROM AUTHOR]

Background: The association between black race and worse outcomes in operable breast cancer reported in previous studies has been attributed to a higher incidence of more aggressive triple-negative disease, disparities in care, and comorbidities. We evaluated associations between black race and outcomes, by tumor hormone receptor and HER2 expression, in patients who were treated with contemporary adjuvant therapy.Methods: The effect of black race on disease-free and overall survival was evaluated using Cox proportional hazards models adjusted for multiple covariates in a clinical trial population that was treated with anthracycline- and taxane-containing chemotherapy. Categorical variables were compared using the Fisher exact test. All P values are two-sided.Results: Of 4817 eligible patients, 405 (8.4%) were black. Compared with nonblack patients, black patients had a higher rate of triple-negative disease (31.9% vs 17.2%; P < .001) and a higher body mass index (median: 31.7 vs 27.4 kg/m(2); P < .001). Black race was statistically significantly associated with worse disease-free survival (5-year disease-free survival, black vs nonblack: 76.7% vs 84.5%; hazard ratio of recurrence or death = 1.58, 95% confidence interval = 1.19 to 2.10, P = .0015) and overall survival (5-year overall survival, black vs nonblack: 87.6% vs 91.9%; hazard ratio of death = 1.49, 95% confidence interval = 1.05 to 2.12, P = .025) in patients with hormone receptor-positive HER2-negative disease but not in patients with triple-negative or HER2-positive disease. In a model that included black race, hormone receptor-positive HER2-negative disease vs other subtypes, and their interaction, the interaction term was statistically significant for disease-free survival (P = .027) but not for overall survival (P = .086).Conclusion: Factors other than disparities in care or aggressive disease contribute to increased recurrence in black women with hormone receptor-positive breast cancer. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the relationships among measures of hot flushes, perceived hot flush interference, sleep disturbance, and measures of quality of life while controlling for potential covariates (patient and treatment variables). Methods Breast cancer survivors ( n == 395) due to receive aromatase inhibitor therapy provided demographic information, physiological hot flush data via sternal skin conductance monitoring, hot flush frequency via written diary and electronic event marker, hot flush severity and bother via written diary, and questionnaire data via the Hot Flash Related Daily Interference Scale, Pittsburgh Sleep Quality Index, the EuroQOL, Hospital Anxiety and Depression Scale and the Center for Epidemiologic Studies Depression Scale. Results Confirmatory factor analysis supported a two-factor model for hot flush symptoms (frequency and severity). Although there was strong convergence among self-reported hot flush measures, there was a high degree of unexplained variance associated with physiological measures. This suggests that self-report and physiological measures do not overlap substantially. The structural model showed that greater hot flush frequency and severity were directly related to greater perceived interference with daily life activities. Greater perceived interference, in turn, directly predicted greater sleep disruption, which predicted lower perceived health state and more symptoms of anxiety and depression. Conclusions Findings suggest hot flush interference may be the most appropriate single measure to include in clinical trials of vasomotor symptom therapies. Measuring and ameliorating patients' perceptions of hot flush interference with life activities and subjective sleep quality may be the most direct routes to improving quality of life. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: The aim of this prospective study was to investigate using multiparametric and multinuclear magnetic resonance imaging during preoperative systemic therapy for locally advanced breast cancer.Materials and Methods: Women with operable stage 2 or 3 breast cancer who received preoperative systemic therapy were studied using dynamic contrast-enhanced magnetic resonance imaging, magnetic resonance spectroscopy, and ²³Na magnetic resonance. Quantitative metrics of choline peak signal-to-noise ratio, total tissue sodium concentration, tumor volumes, and Response Evaluation Criteria in Solid Tumors were determined and compared to final pathologic results using receiver-operating characteristic analysis. Hormonal markers were investigated. Statistical significance was set at P < .05.Results: Eighteen eligible women were studied. Fifteen responded to therapy, four (22%) with pathologic complete response and 11 (61%) with pathologic partial response. Three patients (17%) had no response. Among estrogen receptor-positive, HER2-positive, and triple-negative phenotypes, observed frequencies of pathologic complete response, pathologic partial response, and no response were 2, 5, and 0; 1, 4, and 0; and 1, 1, and 3, respectively. Responders (pathologic complete response and pathologic partial response) had the largest reductions in choline signal-to-noise ratio (35%, from 7.2 ± 2.3 to 4.6 ± 2; P < .01) compared to nonresponders (11%, from 8.4 ± 2.7 to 7.5 ± 3.6; P = .13) after the first cycle. Total tissue sodium concentration significantly decreased in responders (27%, from 66 ± 18 to 48.4 ± 8 mmol/L; P = .01), while there was little change in nonresponders (51.7 ± 7.6 to 56.5 ± 1.6 mmol/L; P = .50). Lesion volume decreased in responders (40%, from 78 ± 78 to 46 ± 51 mm³; P = .01) and nonresponders (21%, from 100 ± 104 to 79.2 ± 87 mm³; P = .23) after the first cycle. The largest reduction in Response Evaluation Criteria in Solid Tumors occurred after the first treatment in responders (18%, from 24.5 ± 20 to 20.2 ± 18 mm; P = .01), with a slight decrease in tumor diameter noted in nonresponders (17%, from 23 ± 19 to 19.2 ± 19.1 mm; P = .80).Conclusions: Multiparametric and multinuclear imaging parameters were significantly reduced after the first cycle of preoperative systemic therapy in responders, specifically, choline signal-to-noise ratio and sodium. These new surrogate radiologic biomarkers maybe able to predict and provide a platform for potential adaptive therapy in patients. [ABSTRACT FROM AUTHOR]

Background: The aromatase inhibitor (AI)-associated musculoskeletal syndrome (AIMSS) occurs in approximately 50% of AI-treated patients. Inflammatory mediators are associated with oestrogen signalling and may change with oestrogen depletion. We hypothesised that AIMSS may be associated with changes in circulating inflammatory markers.Methods: Patients with breast cancer were enrolled in a trial of adjuvant AI therapy. Changes in pain and function during therapy were assessed prospectively. We selected 30 cases with AIMSS and 22 controls without AIMSS, matched for demographics and prior therapy. Serum samples collected at baseline and during treatment were assayed for multiple inflammatory cytokines and lipid mediators using multiplex assays.Results: Before AI therapy, mean serum concentrations of 6 of 36 assayed factors were statistically significantly lower in cases than controls (all P<0.003). No statistically significant changes during AI therapy relative to pre-treatment were observed between cases and controls for any of the inflammatory markers tested.Conclusion: AIMSS is probably not associated with a systemic inflammatory response. Pre-treatment cytokine levels may predict for development of AIMSS. [ABSTRACT FROM AUTHOR]

Accurate assessment of CYP2D6 phenotypes from genotype is inadequate in patients taking CYP2D6 substrate together with CYP2D6 inhibitors. A novel CYP2D6 scoring system is proposed that incorporates the impact of concomitant medications with the genotype in calculating the CYP2D6 activity score. Training (n = 159) and validation (n = 81) data sets were obtained from a prospective cohort tamoxifen pharmacogenetics registry. Two inhibitor factors were defined: 1 genotype independent and 1 genotype based. Three CYP2D6 gene scoring systems, and their combination with the inhibitor factors, were compared. These 3 scores were based on Zineh, Zanger, and Gaedigk's approaches. Endoxifen/NDM-Tam plasma ratio was used as the phenotype. The overall performance of the 3 gene scoring systems without consideration of CYP2D6-inhibiting medications in predicting CYP2D6 phenotype was poor in both the training set (R(2) = 0.24, 0.22, and 0.18) and the validation set (R(2) = 0.30, 0.24, and 0.15). Once the CYP2D6 genotype-independent inhibitor factor was integrated into the score calculation, the R(2) values in the training and validation data sets were nearly twice as high as the genotype-only scoring model: (0.44, 0.43, 0.38) and (0.53, 0.50, 0.41), respectively. The integration of the inhibitory effect of concomitant medications with the CYP2D6 genotype into the composite CYP2D6 activity score doubled the ability to predict the CYP2D6 phenotype. However, endoxifen phenotypes still varied substantially, even with incorporation of CYD2D6 genotype and inhibiting factors, suggesting that other, as yet unidentified factors must be involved in tamoxifen activation. [ABSTRACT FROM AUTHOR]

Neoadjuvant therapy may provide advantages to some women with primary operable breast cancer. Compared to the administration of the same regimen in the adjuvant setting, neoadjuvant chemotherapy does not improve survival outcomes, but may provide other benefits. Neoadjuvant therapy is associated with improved rates of breast-conserving therapy, may offer prognostic information, and enables assessment of in vivo response to therapy. Women who achieve a pathologic complete response following neoadjuvant therapy are expected to have a superior outcome compared to those with extensive residual disease. The neoadjuvant setting has been an attractive area of research for identifying new effective treatment strategies while minimizing treatment-related adverse events, studying drug mechanisms of action, and developing clinically applicable prognostic and predictive biomarkers in an attempt to individualize therapy. In the primary operable setting, it is of great importance to define treatment goals, to select proper candidates for the approach, to assess baseline tumor characteristics, and to provide optimal multidisciplinary monitoring during and following the neoadjuvant therapy. [ABSTRACT FROM AUTHOR]

Background: Tamoxifen, a selective oestrogen receptor (ER) modulator, increases bone mineral density (BMD) in postmenopausal women and decreases BMD in premenopausal women. We hypothesised that inherited variants in candidate genes involved in oestrogen signalling and tamoxifen metabolism might be associated with tamoxifen effects in bone.Methods: A total of 297 women who were initiating tamoxifen therapy were enrolled in a prospective multicentre clinical trial. Lumbar spine and total hip BMD values were measured using dual-energy X-ray absorptiometry (DXA) at baseline and after 12 months of tamoxifen therapy. Single-nucleotide polymorphisms (SNPs) in ESR1, ESR2, and CYP2D6 were tested for associations in the context of menopausal status and previous chemotherapy, with a mean percentage change in BMD over 12 months.Results: The percentage increase in BMD was greater in postmenopausal women and in those patients who had been treated with chemotherapy. No significant associations between tested SNPs and either baseline BMD or change in BMD with 1 year of tamoxifen therapy were detected.Conclusion: The evaluated SNPs in ESR and CYP2D6 do not seem to influence BMD in tamoxifen-treated subjects. [ABSTRACT FROM AUTHOR]

Purpose: Although patients' function, symptoms, and supportive care needs are obviously related, a better understanding of these relationships could improve patient management.Methods: In this cross-sectional, observational study, 117 cancer patients completed the Supportive Care Needs Survey-34 and EORTC-QLQ-C30. Each symptom and function domain from the EORTC-QLQ-C30 was dichotomized (high vs. low) using a cut-off of reference sample mean scores. Each need domain was dichotomized using a cut-off of an average score representing an unmet need. We explored within-patient patterns of function, symptom, and need domains using latent class analysis. Based on these patterns, patients were categorized as high versus low function; high versus low symptom; and high versus low need. We examined the concordance between categorizations of patients' function, symptoms, and needs.Results: The categorizations of function, symptoms, and needs were concordant for 66 patients (56%). Among patients with deficits in at least one area (n = 68), categorizations for 51 patients (75%) were discordant.Conclusions: About 50% of patients have similar classifications of their level of function, symptoms, and needs, but discordance was common among patients with deficits in at least one area, emphasizing the importance of assessing all of these outcomes as part of patient evaluations. [ABSTRACT FROM AUTHOR]

The article discusses studies on breast cancer chemotherapy. A study noted that the progestin megesterol acetate (MA) significantly reduced vasomotor symptoms with durable benefit over six months. A research found that tamoxifen treatment does not reduce the incidence of estrogen receptor (ER)-negative breast cancer. Another study found that treatment with metronomic capecitabine and cyclophosphamide in combination with bevacizumab was effective in advanced breast cancer and was minimally toxic.

The introduction of aromatase inhibitor (AI) therapy for the adjuvant treatment of postmenopausal women with hormone receptor-positive breast cancer has led to a significant change in the management of the disease. AIs are slightly more efficacious and initially appeared to have a better toxicity profile compared to the previous gold standard, tamoxifen. However, increased use of AIs in the community setting has led to the recognition that the clinical impact of the musculoskeletal side effects is substantial. This review will describe the variety of AI-associated musculoskeletal symptoms (AIMSS), potential mechanisms underlying the development of the toxicity, and available treatment options for these side effects. Increased knowledge about the etiology and management of this clinically important toxicity could potentially improve patient adherence to AI therapy, thereby leading to a reduction in breast cancer recurrence and death. [ABSTRACT FROM AUTHOR]

While these drugs can help prevent breast cancer, they also carry the risk of serious complications and affect a patient's quality of life. Three experts offer advice on how to manage these problems. [ABSTRACT FROM AUTHOR]

Disease-free and overall survival have improved significantly for women diagnosed with early-stage breast cancer. At the same time, systemic therapy has only slightly enhanced long-term outcomes in advanced breast cancer, a disease that remains largely incurable. Several single-agent and combination chemotherapy approaches are available to women with hormone-insensitive advanced disease that may improve overall survival and progression-free survival, minimize symptoms and complications related to the disease, and improve overall quality of life. In addition, new cytotoxic and targeted agents have been recently introduced into practice and have improved both survival outcomes and quality of life. In this review, we will provide an update on commonly used chemotherapy-based regimens for the treatment of metastatic breast cancer, with a focus on tailoring therapy to different subtypes of the disease. [ABSTRACT FROM AUTHOR]

This article presents comments on various studies related to breast cancer. It includes "Vaccination With a HER2/neu Peptide Induces Intra- and Inter-Antigenic Epitope Spreading in Patients With Early Stage Breast Cancer," "A Phase II Trial of Pemetrexed in Advanced Breast Cancer: Clinical Response and Association With Molecular Target Expression" and "HER2 and Responsiveness of Breast Cancer in Adjuvant Chemotherapy."

Almost every woman and some men will encounter hot flushes during their lifetime. Despite the prevalence of the symptoms, the pathophysiology of hot flushes remains unknown. A decline in hormone concentrations might lead to alterations in brain neurotransmitters and to instability in the hypothalamic thermoregulatory setpoint. The most effective treatments for hot flushes include oestrogens and progestagens. However, many women and their physicians are reluctant to accept hormonal treatments. Women want non-pharmacological treatments but unfortunately such treatments are not very effective, and non-hormonal drugs are often associated with adverse effects. Results from recent studies showed that selective serotonin reuptake inhibitors and other similar compounds can safely reduce hot flushes. Moreover, the efficacy of these drugs provides new insight into the pathophysiology of hot flushes. In this critical review, we assess knowledge of the epidemiology, pathophysiology, and treatment of hot flushes. [ABSTRACT FROM AUTHOR]

The article discusses a study on the influence of cytochrome P450 2D6 (CYP2D6) inhibitors on breast cancer outcomes in women prescribed with tamoxifen. It references a study by T. P. Ahern et al in "Cancer Epidemiology, Biomarkers and Prevention." It was found that the effectiveness of tamoxifen in reducing recurrence risk among women treated for estrogen receptor-positive breast cancer partly depends on metabolic activation via CYP2D6. A null association between CYP2D6 activity and breast cancer recurrence among tamoxifen-treated women was observed.

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The article discusses research which examines the predictive value of genetic variants of CYP2D6, CYP2C19 and other cytochrome P450 enzymes for tamoxifen treatment outcome among breast cancer patients. It references a study by W. Schroth et al. published in a 2007 issue of "Journal of Clinical Oncology." Results show that tamoxifen-treated patients carrying the CYP2D6 alleles *4, *5, *10, *41 had more recurrences of breast cancer, shorter relapse-free periods, and worse event-free survival rates compared with carriers of functional alleles.