Weight management and its role in breast cancer rehabilitation

Overweight and obesity are risk factors for post-menopausal breast cancer, and many women diagnosed with breast cancer, irrespective of menopausal status, gain weight after diagnosis. Weight management plays an important role in rehabilitation and recovery since obesity and/or weight gain may lead to poorer breast cancer prognosis, as well as prevalent co-morbid conditions (e.g. cardiovascular disease and diabetes), poorer surgical outcomes (e.g., increased operating and recovery times, higher infection rates, and poorer healing), lymphedema, fatigue, functional decline, and poorer health and overall quality of life. Health care professionals should encourage weight management at all phases of the cancer care continuum as a means to potentially avoid adverse sequelae and late effects, as well as to improve overall health and possibly survival. Comprehensive approaches that involve dietary and behavior modification, and increased aerobic and strength training exercise have shown promise in either preventing weight gain or promoting weight loss, reducing biomarkers associated with inflammation and co-morbidity, and improving lifestyle behaviors, functional status, and quality of life in this high-risk patient population.

Younger and older women's concerns about menopause after breast cancer

A number of treatments for breast cancer induce menopause. This study's aim was to explore women's perceptions and beliefs about menopausal symptoms and their management following breast cancer, and to compare younger and older women's experiences. Data were collected via semi-structured focus groups from women who had undergone treatment for breast cancer, and who were currently experiencing menopausal symptoms. Data were interpreted by way of simple inductive thematic analysis. The women experienced a range of menopausal symptoms that they were not prepared for and found difficult to manage. The central themes related to their lack of knowledge of how to manage menopausal symptoms, and the distress and helplessness that arose from this. Women who were diagnosed prior to 40 years of age reported additional menopausal issues than women who were older at diagnosis. The women in this study expressed a thirst for information related to menopause after breast cancer. The women identified that their needs with regard to menopause after breast cancer were not being met, either through their own lack of knowledge or via conflicting or absent support and management. The importance of enabling women to deal with menopausal symptoms was a central theme to emerge from the data.

Information interventions for orienting patients and their carers to cancer care facilities

Background: Cancer patients experience distress and anxiety related to their diagnosis, treatment and the unfamiliar cancer centre. Strategies with the aim of orienting patients to a cancer care facility may improve patient outcomes. Although meeting patients' information needs at different stages is important, there is little agreement about the type of information and the timing for information to be given. Orientation interventions aim to address information needs at the start of a person's experience with a cancer care facility. The extent of any benefit of these interventions is unknown. Objectives: To assess the effects of information interventions which orient patients and their carers/family to a cancer care facility, and to the services available in the facility. Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2); MEDLINE (OvidSP) (1966 to Jun 2011), EMBASE (Ovid SP) (1966 to Jun 2011), CINAHL (EBSCO) (1982 to Jun 2011), PsycINFO (OvidSP) (1966 to Jun 2011), review articles and reference lists of relevant articles. We contacted principal investigators and experts in the field. Selection Criteria: Randomised controlled trials (RCTs), cluster RCTs and quasi-RCTs evaluating the effects of information interventions that orient patients and their carers/family to a cancer care facility. Data collection and analysis: Results of searches were reviewed against the pre-determined criteria for inclusion by two review authors. The primary outcomes were knowledge and understanding; health status and wellbeing, evaluation of care, and harms. Secondary outcomes were communication, skills acquisition, behavioural outcomes, service delivery, and health professional outcomes. We pooled results of RCTs using mean differences (MD) and 95% confidence intervals (CI). Main results: We included four RCTs involving 610 participants. All four trials aimed to investigate the effects of orientation programs for cancer patients to a cancer facility. There was high risk of bias across studies. Findings from two of the RCTs demonstrated significant benefits of the orientation intervention in relation to levels of distress (mean difference (MD) -8.96 (95% confidence interval (CI) -11.79 to -6.13), but non-significant benefits in relation to state anxiety levels (MD -9.77 (95% CI -24.96 to 5.41). Other outcomes for participants were generally positive (e.g. more knowledgeable about the cancer centre and cancer therapy, better coping abilities). No harms or adverse effects were measured or reported by any of the included studies. There were insufficient data on the other outcomes of interest. Authors conclusion: This review has demonstrated the feasibility and some potential benefits of orientation interventions. There was a low level of evidence suggesting that orientation interventions can reduce distress in patients. However, most of the other outcomes remain inconclusive (patient knowledge recall/ satisfaction). The majority of studies were subject to high risk of bias, and were likely to be insufficiently powered. Further well conducted and powered RCTs are required to provide evidence for determining the most appropriate intensity, nature, mode and resources for such interventions. Patient and carer-focused outcomes should be included.

Clusterin facilitates COMMD1 and I-kB degradation to enhance NF-kB activity in prostate cancer cells

Secretory clusterin (sCLU) is a stress-activated, cytoprotective chaperone that confers broad-spectrum cancer treatment resistance, and its targeted inhibitor (OGX-011) is currently in phase II trials for prostate, lung, and breast cancer. However, the molecular mechanisms by which sCLU inhibits treatment-induced apoptosis in prostate cancer remain incompletely defined. We report that sCLU increases NF-κB nuclear translocation and transcriptional activity by serving as a ubiquitin-binding protein that enhances COMMD1 and I-κB proteasomal degradation by interacting with members of the SCF-βTrCP E3 ligase family. Knockdown of sCLU in prostate cancer cells stabilizes COMMD1 and I-κB, thereby sequestrating NF-κB in the cytoplasm and decreasing NF-κB transcriptional activity. Comparative microarray profiling of sCLU-overexpressing and sCLU-knockdown prostate cancer cells confirmed that the expression of many NF-κB–regulated genes positively correlates with sCLU levels. We propose that elevated levels of sCLU promote prostate cancer cell survival by facilitating degradation of COMMD1 and I-κB, thereby activating the canonical NF-κB pathway.

Exercise for breast cancer survivors: bridging the gap between evidence and practice

Evidence supporting the benefits of exercise following the diagnosis of breast cancer is overwhelming and compelling. Exercise reduces the severity and number of treatment-related side effects, optimizes quality of life during and following treatment, and may optimize survival. Yet, exercise does not uniformly form part of the standards of care provided to women following a breast cancer diagnosis. This commentary summarizes the evidence in support of exercise as a form of adjuvant treatment and identifies and discusses potential issues preventing the formal integration of exercise into breast cancer care. Proposed within the commentary is a model of breast cancer care that incorporates exercise prescription as a key component but also integrates the need for surveillance and management for common breast cancer treatment-related morbidities, as well as education. While future research evaluating the potential cost savings through implementation of such amodel is required, a committed, collaborative approach by clinicians, allied health professionals, and researchers will be instrumental in bridging the gap between research and practice.

A randomized trial of a telephone-delivered exercise intervention for non-urban dwelling women newly diagnosed with breast cancer : exercise for health

Physical activity is important following breast cancer. Trials of non-face-to-face interventions are needed to assist in reaching women living outside major metropolitan areas. This study seeks to evaluate the feasibility and effectiveness of a telephone-delivered, mixed aerobic and resistance exercise intervention for non-urban Australian women with breast cancer. A randomized controlled trial comparing an 8-month intervention delivered by exercise physiologists (n = 73) to usual care (n = 70). Sixty-one percent recruitment rate and 96% retention at 12 months; 79% of women in the intervention group received at least 75% of calls; odds (OR, 95% CI) of meeting intervention targets favored the intervention group for resistance training (OR 3.2; 1.2, 8.9) and aerobic (OR 2.1; 0.8, 5.5) activity. Given the limited availability of physical activity programs for non-urban women with breast cancer, results provide strong support for feasibility and modest support for the efficacy of telephone-delivered interventions.

A novel duplication polymorphism in the FANCA promoter and its association with breast and ovarian cancer

The FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a rare autosomal recessive disorder characterised by congenital abnormalities, bone marrow failure, and predisposition to malignancy. FANCA is also a potential breast and ovarian cancer susceptibility gene. A novel allele was identified which has a tandem duplication of a 13 base pair sequence in the promoter region. Methods: We screened germline DNA from 352 breast cancer patients, 390 ovarian cancer patients and 256 normal controls to determine if the presence of either of these two alleles was associated with an increased risk of breast or ovarian cancer. Results: The duplication allele had a frequency of 0.34 in the normal controls. There was a nonsignificant decrease in the frequency of the duplication allele in breast cancer patients. The frequency of the duplication allele was significantly decreased in ovarian cancer patients. However, when malignant and benign tumours were considered separately, the decrease was only significant in benign tumours. Conclusion: The allele with the tandem duplication does not appear to modify breast cancer risk but may act as a low penetrance protective allele for ovarian cancer.

CgDN24 : a gene involved in hyphal development in the fungal phytopathogen Colletotrichum gloeosporioides

A cDNA corresponding to a transcript induced in culture by N starvation, was identified in Colletotrichum gloeosporioides by a differential hybridisation strategy. The cDNA comprised 905 bp and predicted a 215 aa protein; the gene encoding the cDNA was termed CgDN24. No function for CgDN24 could be predicted by database homology searches using the cDNA sequence and no homologues were found in the sequenced fungal genomes. Transcripts of CgDN24 were detected in infected leaves of Stylosanthes guianensis at stages of infection that corresponded with symptom development. The CgDN24 gene was disrupted by homologous recombination and this led to reduced radial growth rates and the production of hyphae with a hyperbranching phenotype. Normal sporulation was observed, and following conidial inoculation of S. guianensis, normal disease development was obtained. These results demonstrate that CgDN24 is necessary for normal hyphal development in axenic culture but dispensable for phytopathogenicity. © 2005 Elsevier GmbH. All rights reserved.

Investigation of the expression of the EphB4 receptor tyrosine kinase in prostate carcinoma

Background: The EphB4 receptor tyrosine kinase has been reported as increased in tumours originating from several different tissues and its expression in a prostate cancer xenograft model has been reported. Methods: RT-PCR, western blotting and immunohistochemical techniques were used to examine EphB4 expression and protein levels in human prostate cancer cell lines LNCaP, DU145 and PC3. Immunohistochemistry was also used to examine localisation of EphB4 in tissue samples from 15 patients with prostate carcinomas. Results: All three prostate cancer cell lines expressed the EphB4 gene and protein. EphB4 immunoreactivity in vivo was significantly greater in human prostate cancers as compared with matched normal prostate epithelium and there appeared to be a trend towards increased expression with higher grade disease. Conclusions: EphB4 is expressed in prostate cancer cell lines with increased expression in human prostate cancers when compared with matched normal tissue. EphB4 may therefore be a useful anti-prostate cancer target. © 2005 Lee et al., licensee BioMed Central Ltd.

Identification of early-stage colorectal cancer patients at risk of relapse post-resection by immunobead reverse transcription-PCR analysis of peritoneal lavage fluid for malignant cells

Purpose: Colorectal cancer patients diagnosed with stage I or II disease are not routinely offered adjuvant chemotherapy following resection of the primary tumor. However, up to 10% of stage I and 30% of stage II patients relapse within 5 years of surgery from recurrent or metastatic disease. The aim of this study was to determine if tumor-associated markers could detect disseminated malignant cells and so identify a subgroup of patients with early-stage colorectal cancer that were at risk of relapse. Experimental Design: We recruited consecutive patients undergoing curative resection for early-stage colorectal cancer. Immunobead reverse transcription-PCR of five tumor-associated markers (carcinoembryonic antigen, laminin γ2, ephrin B4, matrilysin, and cytokeratin 20) was used to detect the presence of colon tumor cells in peripheral blood and within the peritoneal cavity of colon cancer patients perioperatively. Clinicopathologic variables were tested for their effect on survival outcomes in univariate analyses using the Kaplan-Meier method. A multivariate Cox proportional hazards regression analysis was done to determine whether detection of tumor cells was an independent prognostic marker for disease relapse. Results: Overall, 41 of 125 (32.8%) early-stage patients were positive for disseminated tumor cells. Patients who were marker positive for disseminated cells in post-resection lavage samples showed a significantly poorer prognosis (hazard ratio, 6.2; 95% confidence interval, 1.9-19.6; P = 0.002), and this was independent of other risk factors. Conclusion: The markers used in this study identified a subgroup of early-stage patients at increased risk of relapse post-resection for primary colorectal cancer. This method may be considered as a new diagnostic tool to improve the staging and management of colorectal cancer. © 2006 American Association for Cancer Research.

A prospective surveillance model for rehabilitation for women with breast cancer

Background: The current model of care for breast cancer is focused on disease treatment followed by ongoing recurrence surveillance. This approach lacks attention to the patients’ physical and functional well-being. Breast cancer treatment sequelae can lead to physical impairments and functional limitations. Common impairments include pain, fatigue, upper extremity dysfunction, lymphedema, weakness, joint arthralgia, neuropathy, weight gain, cardiovascular effects, and osteoporosis. Evidence supports prospective surveillance for early identification and treatment as a means to prevent or mitigate many of these concerns. Purpose: This paper proposes a prospective surveillance model for physical rehabilitation and exercise that can be integrated with disease treatment to create a more comprehensive approach to survivorship health care. The goals of the model are to promote surveillance for common physical impairments and functional limitations associated with breast cancer treatment, to provide education to facilitate early identification of impairments, to introduce rehabilitation and exercise intervention when physical impairments are identified and to promote and support physical activity and exercise behaviors through the trajectory of disease treatment and survivorship. Methods: The model is the result of a multi-disciplinary meeting of research and clinical experts in breast cancer survivorship and representatives of relevant professional and advocacy organizations. Outcomes: The proposed model identifies time points during breast cancer care for assessment of and education about physical impairments. Ultimately, implementation of the model may influence incidence and severity of breast cancer treatment related physical impairments. As such, the model seeks to optimize function during and following treatment and positively influence a growing survivorship community.