Amelioration of sexual adverse effects in the early breast cancer patient

As the number of breast cancer survivors increases, the long term consequences of breast cancer treatment are gaining attention. Sexual dysfunction is a common complaint amongst breast cancer survivors, and there are few evidence based recommendations and even fewer well designed clinical trials to establish what treatments are safe or effective in this patient population. We conducted a PubMed search for articles published between 1995–2009 containing the terms breast cancer, sexual dysfunction, libido, vaginal dryness, testosterone, and vaginal estrogen. We initially reviewed articles focusing exclusively on sexual issues in breast cancer patients. Given the paucity of clinical trials addressing sexual issues in breast cancer patients, we also included studies evaluating both hormone and non-hormone based interventions for sexual dysfunction in post-menopausal women in general. Among breast cancer survivors, vaginal dryness and loss of libido represent some of the most challenging long term side effects of breast cancer treatment. In the general post-menopausal population, topical preparations of estrogens and testosterone both appear to improve sexual function; however there are conflicting reports about the efficacy and safety of these interventions in women with a history of breast cancer, and further research is warranted

Hypnosis for hot flashes among postmenopausal women study: A study protocol of an ongoing randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Hot flashes are a highly prevalent problem associated with menopause and breast cancer treatments. The recent findings from the Women's Health Initiative have important implications for the significance of a non-hormonal, mind-body intervention for hot flashes in breast cancer survivors. Women who take hormone therapy long-term may have a 1.2 to 2.0 fold increased risk of developing breast cancer. In addition, it is now known that hormone therapy with estrogen and progestin is associated with increased risk of cardiovascular disease and stroke. Currently there are limited options to hormone replacement therapy as non-hormonal pharmacological agents are associated with only modest activity and many adverse side effects. Because of this there is a need for more alternative, non-hormonal therapies. Hypnosis is a mind-body intervention that has been shown to reduce self-reported hot flashes by up to 68% among breast cancer survivors, however, the use of hypnosis for hot flashes among post-menopausal women has not been adequately explored and the efficacy of hypnosis in reducing physiologically measured hot flashes has not yet been determined.</p> <p>Methods/design</p> <p>A sample of 180 post-menopausal women will be randomly assigned to either a 5-session Hypnosis Intervention or 5-session structured-attention control with 12 week follow-up. The present study will compare hypnosis to a structured-attention control in reducing hot flashes (perceived and physiologically monitored) in post-menopausal women in a randomized clinical trial. Outcomes will be hot flashes (self-report daily diaries; physiological monitoring; Hot Flash Related Daily Interference Scale), anxiety (State-Trait Anxiety Inventory; Hospital Anxiety and Depression Scale (HADS); anxiety visual analog scale (VAS rating); depression (Center for Epidemiologic Studies Depression Scale), sexual functioning (Sexual Activity Questionnaire), sleep quality (Pittsburgh Sleep Quality Index) and cortisol.</p> <p>Discussion</p> <p>This study will be the first full scale test of hypnosis for hot flashes; one of the first studies to examine both perceived impact and physiologically measured impact of a mind-body intervention for hot flashes using state-of-the-art 24 hour ambulatory physiological monitoring; the first study to examine the effect of hypnosis for hot flashes on cortisol; and the first investigation of the role of cognitive expectancies in treatment of hot flashes in comparison to a Structured-Attention Control.</p> <p>Trial Registration</p> <p>This clinical trial has been registered with ClinicalTrials.gov, a service of the U.S. National Institutes of Health, ClinicalTrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01293695">NCT01293695</a>.</p

Switching to letrozole or exemestane improves hot flushes, mood and quality of life in tamoxifen intolerant women

We report an open-label, prospective, crossover study involving 184 post-menopausal women experiencing hot flushes on adjuvant tamoxifen (T). Six weeks after switching to an AI, the primary end point, hot flush score, improved by 47.3% (P<0.001) compared to those reported on T. The mean mood rating scale (MRS) score improved by 9.7% (P=0.01). The total mean combined FACT (b+es) score improved from 134.2 (95% CI ±2.96) to 143.5 (95% CI ±2.96 <0.001), and the endocrine subscale improved by 9.8% from 51.73 (95% CI ±1.38) to 57.34 (CI ±1.38, P<0.001). At 6 weeks, significantly more women chose to remain on an AI: 133 (72%), vs 40 (22%) (P<0.001) preferring T. At 3 months, 107 (58%) preferred to remain on an AI, 55(30%) on T, and 22 (12%) withdrew. The overall arthralgia rate at 3 months was 47% on AI and 30% on T (P=0.001). In all 182 (99%) women reported appreciating the opportunity to experience both drugs. These data suggest that if patients suffering significant adverse effects on T are given the opportunity to try an AI, this empowers them to prioritise relative side-effects, improving wellbeing in a significant proportion. These data also highlight the need for hospital follow-up in this intolerant cohort

A model building exercise of mortality risk for Taiwanese women with breast cancer

Abstract Background The accurate estimation of outcome in patients with malignant disease is an essential component of the optimal treatment, decision-making and patient counseling processes. The prognosis and disease outcome of breast cancer patients can differ according to geographic and ethnic factors. To our knowledge, to date these factors have never been validated in a homogenous loco-regional patient population, with the aim of achieving accurate predictions of outcome for individual patients. To clarify this topic, we created a new comprehensive prognostic and predictive model for Taiwanese breast cancer patients based on a range of patient-related and various clinical and pathological-related variables. Methods Demographic, clinical, and pathological data were analyzed from 1 137 patients with breast cancer who underwent surgical intervention. A survival prediction model was used to allow analysis of the optimal combination of variables. Results The area under the receiver operating characteristic (ROC) curve, as applied to an independent validation data set, was used as the measure of accuracy. Results were compared by comparing the area under the ROC curve. Conclusions our model building exercise of mortality risk was able to predict disease outcome for individual patients with breast cancer. This model could represent a highly accurate prognostic tool for Taiwanese breast cancer patients.</p

Method for evaluating prediction models that apply the results of randomized trials to individual patients

<p>Abstract</p> <p>Introduction</p> <p>The clinical significance of a treatment effect demonstrated in a randomized trial is typically assessed by reference to differences in event rates at the group level. An alternative is to make individualized predictions for each patient based on a prediction model. This approach is growing in popularity, particularly for cancer. Despite its intuitive advantages, it remains plausible that some prediction models may do more harm than good. Here we present a novel method for determining whether predictions from a model should be used to apply the results of a randomized trial to individual patients, as opposed to using group level results.</p> <p>Methods</p> <p>We propose applying the prediction model to a data set from a randomized trial and examining the results of patients for whom the treatment arm recommended by a prediction model is congruent with allocation. These results are compared with the strategy of treating all patients through use of a net benefit function that incorporates both the number of patients treated and the outcome. We examined models developed using data sets regarding adjuvant chemotherapy for colorectal cancer and Dutasteride for benign prostatic hypertrophy.</p> <p>Results</p> <p>For adjuvant chemotherapy, we found that patients who would opt for chemotherapy even for small risk reductions, and, conversely, those who would require a very large risk reduction, would on average be harmed by using a prediction model; those with intermediate preferences would on average benefit by allowing such information to help their decision making. Use of prediction could, at worst, lead to the equivalent of an additional death or recurrence per 143 patients; at best it could lead to the equivalent of a reduction in the number of treatments of 25% without an increase in event rates. In the Dutasteride case, where the average benefit of treatment is more modest, there is a small benefit of prediction modelling, equivalent to a reduction of one event for every 100 patients given an individualized prediction.</p> <p>Conclusion</p> <p>The size of the benefit associated with appropriate clinical implementation of a good prediction model is sufficient to warrant development of further models. However, care is advised in the implementation of prediction modelling, especially for patients who would opt for treatment even if it was of relatively little benefit.</p

A prospective randomized study of megestrol acetate and ibuprofen in gastrointestinal cancer patients with weight loss

The use of megestrol acetate in the treatment of weight loss in gastrointestinal cancer patients has been disappointing. The aim of the present study was to compare the combination of megestrol acetate and placebo with megestrol acetate and ibuprofen in the treatment of weight loss in such patients. At baseline, 4–6 weeks and 12 weeks, patients underwent measurements of anthropometry, concentrations of albumin and C-reactive protein and assessment of appetite, performance status and quality of life using EuroQol-EQ-5D and EORTC QLQ-C30. Thirty-eight and 35 patients (median weight loss 18%) were randomized to megestrol acetate/placebo or megestrol acetate/ibuprofen, respectively, for 12 weeks. Forty-six (63%) of patients failed to complete the 12-week assessment. Of those evaluable at 12 weeks, there was a decrease in weight (median 2.8 kg) in the megestrol acetate/placebo group compared with an increase (median 2.3 kg) in the megestrol acetate/ibuprofen group (P < 0.001). There was also an improvement in the EuroQol-EQ-5D quality of life scores of the latter group (P < 0.05). The combination of megestrol acetate/ibuprofen appeared to reverse weight loss and appeared to improve quality of life in patients with advanced gastrointestinal cancer. Further trials of this novel regimen in weight-losing patients with hormone-insensitive cancers are warranted. © 1999 Cancer Research Campaig

DR6 as a Diagnostic and Predictive Biomarker in Adult Sarcoma

The Death Receptor 6 (DR6) protein is elevated in the serum of ovarian cancer patients. We tested DR6 serum protein levels as a diagnostic/predictive biomarker in several epithelial tumors and sarcomas.DR6 gene expression profiles were screened in publically available arrays of solid tumors. A quantitative immunofluorescent western blot analysis was developed to test the serum of healthy controls and patients with sarcoma, uterine carcinosarcoma, bladder, liver, and pancreatic carcinomas. Change in DR6 serum levels was used to assay the ability of DR6 to predict the response to therapy of sarcoma patients.DR6 mRNA is highly expressed in all tumor types assayed. Western blot analysis of serum DR6 protein demonstrated high reproducibility (r = 0.97). Compared to healthy donor controls, DR6 serum levels were not elevated in patients with uterine carcinosarcoma, bladder, liver, or pancreatic cancers. Serum DR6 protein levels from adult sarcoma patients were significantly elevated (p<0.001). This was most evident for patients with synovial sarcoma. Change in serum DR6 levels during therapy correlated with clinical benefit from therapy (sensitivity 75%, and positive predictive value 87%).DR6 may be a clinically useful diagnostic and predictive serum biomarker for some adult sarcoma subtypes.Diagnosis of sarcoma can be difficult and can lead to improper management of these cancers. DR6 serum protein may be a tool to aid in the diagnosis of some sarcomatous tumors to improve treatment planning. For patients with advanced disease, rising DR6 levels predict non-response to therapy and may expedite therapeutic decision making and reduce reliance on radiologic imaging

Factors associated with cancer-related fatigue in breast cancer patients undergoing endocrine therapy in an urban setting: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Fatigue is prevalent in breast cancer survivors and has profound effects on daily life. The interference of fatigue with endocrine therapy may be difficult to separate. This study investigates the prevalence and severity of fatigue and identifies the demographic, clinical, and lifestyle factors associated with cancer-related fatigue (CRF) in breast cancer patients undergoing endocrine therapy in an urban area.</p> <p>Methods</p> <p>Women with stage I-IIIA breast cancer were recruited and asked to participate (n = 371) in the study. The 315 women who responded to the questionnaire (84.9%), 54 (17.1%) had completed endocrine therapy and 261 (82.9%) were still undergoing endocrine therapy. The patients had been diagnosed at an average of 31 months prior to recruitment (range, 7 to 60 months); the average age was 48 (range, 33 to 72) years. The 11-point scale and Visual Analog Scale (VAS) were employed to quantify the level of fatigue experienced by the patients. Logistic regression analyses and a trend test method were performed to evaluate factors associated with CRF.</p> <p>Results</p> <p>Among the 315 patients, 189 (60%) had experienced or were experiencing CRF during endocrine therapy. Logistic regression analysis was performed to identify factors associated with CRF, including BMI (body mass index), clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet. Factors unrelated to CRF were age, marital status, treatment, endocrine therapy drugs, alcohol intake, and smoking. The trend test method revealed an association between physical activity and dietary level and the intensity of CRF.</p> <p>Conclusions</p> <p>The present findings suggest that fatigue is an important problem in the majority of breast cancer patients during endocrine therapy. We found that BMI, clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet are associated with fatigue. Future research should focus on the impact factors of CRF and lifestyle in the management of breast cancer patients.</p

Prognostic value of monitoring tumour markers CA 15-3 and CEA during fulvestrant treatment

BACKGROUND: At many centres tumour markers are used to detect disease recurrence and to monitor response to therapy in patients with advanced disease, although the real value of serial observation of marker levels remains disputed. In this study, we evaluated the prognostic value of tumour markers for predicting response (partial response [PR], stable disease [SD] ≥ 6 months), de novo disease progression (PD) and secondary PD in patients receiving fulvestrant ('Faslodex') 250 mg/month for the treatment of metastatic breast cancer (MBC). METHODS: Changes in cancer antigen 15–3 (CA 15-3) and carcinoembryonic antigen (CEA) were prospectively monitored (monthly) and were also evaluated for the 3 months preceding secondary PD. Data from 67 patients with previously treated MBC participating in a Compassionate Use Programme were analysed. RESULTS: In patients with a PR (n = 7 [10.4%]), a non-significant increase in CA 15-3 occurred during the first 6 months of treatment; CEA was significantly reduced (P = 0.0165). In patients with SD ≥ 6 months (n = 28 [41.8%]), both CA 15-3 (P < 0.0001) and CEA (P = 0.0399) levels increased significantly after 6 months treatment. In those experiencing de novo PD (n = 32 [47.8%]), CA 15-3 increased significantly (P < 0.0001) after 4 months; CEA also increased significantly (P = 0.0002) during the same time period. Both CA 15-3 (P < 0.0001) and CEA (P < 0.0001) increased significantly in the 3 months preceding secondary PD. CONCLUSION: CA 15-3 increases in patients progressing on fulvestrant but may also increase in those experiencing clinical benefit; this should not be taken as a sign of PD without verification. Overall, both CA 15-3 and CEA appear to be poor prognostic markers for determining progression in patients receiving fulvestrant

Older adults' beliefs about physician-estimated life expectancy: a cross-sectional survey

BACKGROUND: Estimates of life expectancy assist physicians and patients in medical decision-making. The time-delayed benefits for many medical treatments make an older adult's life expectancy estimate particularly important for physicians. The purpose of this study is to assess older adults' beliefs about physician-estimated life expectancy. METHODS: We performed a mixed qualitative-quantitative cross-sectional study in which 116 healthy adults aged 70+ were recruited from two local retirement communities. We interviewed them regarding their beliefs about physician-estimated life expectancy in the context of a larger study on cancer screening beliefs. Semi-structured interviews of 80 minutes average duration were performed in private locations convenient to participants. Demographic characteristics as well as cancer screening beliefs and beliefs about life expectancy were measured. Two independent researchers reviewed the open-ended responses and recorded the most common themes. The research team resolved disagreements by consensus. RESULTS: This article reports the life-expectancy results portion of the larger study. The study group (n = 116) was comprised of healthy, well-educated older adults, with almost a third over 85 years old, and none meeting criteria for dementia. Sixty-four percent (n = 73) felt that their physicians could not correctly estimate their life expectancy. Sixty-six percent (n = 75) wanted their physicians to talk with them about their life expectancy. The themes that emerged from our study indicate that discussions of life expectancy could help older adults plan for the future, maintain open communication with their physicians, and provide them knowledge about their medical conditions. CONCLUSION: The majority of the healthy older adults in this study were open to discussions about life expectancy in the context of discussing cancer screening tests, despite awareness that their physicians' estimates could be inaccurate. Since about a third of participants perceived these discussions as not useful or even harmful, physicians should first ascertain patients' preferences before discussing their life expectancies