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.

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.

Possible genetic predisposition to lymphedema after breast cancer

Background: Known risk factors for secondary lymphedema only partially explain who develops lymphedema following cancer, suggesting that inherited genetic susceptibility may influence risk. Moreover, identification of molecular signatures could facilitate lymphedema risk prediction prior to surgery or lead to effective drug therapies for prevention or treatment. Recent advances in the molecular biology underlying development of the lymphatic system and related congenital disorders implicate a number of potential candidate genes to explore in relation to secondary lymphedema. Methods and Results: We undertook a nested case-control study, with participants who had developed lymphedema after surgical intervention within the first 18 months of their breast cancer diagnosis serving as cases (n=22) and those without lymphedema serving as controls (n=98), identified from a prospective, population-based, cohort study in Queensland, Australia. TagSNPs that covered all known genetic variation in the genes SOX18, VEGFC, VEGFD, VEGFR2, VEGFR3, RORC, FOXC2, LYVE1, ADM and PROX1 were selected for genotyping. Multiple SNPs within three receptor genes, VEGFR2, VEGFR3 and RORC, were associated with lymphedema defined by statistical significance (p<0.05) or extreme risk estimates (OR<0.5 or >2.0). Conclusions: These provocative, albeit preliminary, findings regarding possible genetic predisposition to secondary lymphedema following breast cancer treatment warrant further attention for potential replication using larger datasets.

CAD/CAm-assisted breast reconstruction

The application of computer-aided design and manufacturing (CAD/CAM) techniques in the clinic is growing slowly but steadily. The ability to build patient-specific models based on medical imaging data offers major potential. In this work we report on the feasibility of employing laser scanning with CAD/CAM techniques to aid in breast reconstruction. A patient was imaged with laser scanning, an economical and facile method for creating an accurate digital representation of the breasts and surrounding tissues. The obtained model was used to fabricate a customized mould that was employed as an intra-operative aid for the surgeon performing autologous tissue reconstruction of the breast removed due to cancer. Furthermore, a solid breast model was derived from the imaged data and digitally processed for the fabrication of customized scaffolds for breast tissue engineering. To this end, a novel generic algorithm for creating porosity within a solid model was developed, using a finite element model as intermediate.

UHT milk contains multiple forms of αS1-casein that undergo degradative changes during storage

Milk proteins are susceptible to chemical changes during processing and storage. We used proteomic tools to analyse bovine αS1-casein in UHT milk. 2-D gels of freshly processed milk αS1-casein was presented as five or more spots due to genetic polymorphism and variable phosphorylation. MS analysis after phosphopeptide enrichment allowed discrimination between phosphorylation states and genetic variants. We identified a new alternatively-spliced isoform with a deletion of exon 17, producing a new C-terminal sequence, K164SQVNSEGLHSYGL177, with a novel phosphorylation site at S174. Storage of UHT milk at elevated temperatures produced additional, more acidic αS1-casein spots on the gels and decreased the resolution of minor forms. MS analysis indicated that non-enzymatic deamidation and loss of the N-terminal dipeptide were the major contributors to the changing spot pattern. These results highlight the important role of storage temperature in the stability of milk proteins and the utility of proteomic techniques for analysis of proteins in food.

A multilevel investigation of inequalities in clinical and psychosocial outcomes for women after breast cancer

Background In Australia, breast cancer is the most common cancer affecting Australian women. Inequalities in clinical and psychosocial outcomes have existed for some time, affecting particularly women from rural areas and from areas of disadvantage. We have a limited understanding of how individual and area-level factors are related to each other, and their associations with survival and other clinical and psychosocial outcomes. Methods/Design This study will examine associations between breast cancer recurrence, survival and psychosocial outcomes (e.g. distress, unmet supportive care needs, quality of life). The study will use an innovative multilevel approach using area-level factors simultaneously with detailed individual-level factors to assess the relative importance of remoteness, socioeconomic and demographic factors, diagnostic and treatment pathways and processes, and supportive care utilization to clinical and psychosocial outcomes. The study will use telephone and self-administered questionnaires to collect individual-level data from approximately 3, 300 women ascertained from the Queensland Cancer Registry diagnosed with invasive breast cancer residing in 478 Statistical Local Areas Queensland in 2011 and 2012. Area-level data will be sourced from the Australian Bureau of Statistics census data. Geo-coding and spatial technology will be used to calculate road travel distances from patients' residence to diagnostic and treatment centres. Data analysis will include a combination of standard empirical procedures and multilevel modelling. Discussion The study will address the critical question of: what are the individual- or area-level factors associated with inequalities in outcomes from breast cancer? The findings will provide health care providers and policy makers with targeted information to improve the management of women with breast cancer, and inform the development of strategies to improve psychosocial care for women with breast cancer.

Prevalence and prognostic significance of secondary lymphedema following breast cancer

Background The adverse consequences of lymphedema following breast cancer in relation to physical function and quality of life are clear; however, its potential relationship with survival has not been investigated. Our purpose was to determine the prevalence of lymphedema and associated upper-body symptoms at 6 years following breast cancer and to examine the prognostic significance of lymphedema with respect to overall 6-year survival (OS). Methods and Results A population-based sample of Australian women (n=287) diagnosed with invasive, unilateral breast cancer was followed for a median of 6.6 years and prospectively assessed for lymphedema (using bioimpedance spectroscopy [BIS], sum of arm circumferences [SOAC], and self-reported arm swelling), a range of upper-body symptoms, and vital status. OS was measured from date of diagnosis to date of death or last follow-up. Kaplan-Meier methods were used to calculate OS and Cox proportional hazards models quantified the risk associated with lymphedema. Approximately 45% of women had reported at least one moderate to extreme symptom at 6.6 years postdiagnosis, while 34% had shown clinical evidence of lymphedema, and 48% reported arm swelling at least once since baseline assessment. A total of 27 (9.4%) women died during the follow-up period, and lymphedema, diagnosed by BIS or SOAC between 6–18 months postdiagnosis, predicted mortality (BIS: HR=2.5; 95% CI: 0.9, 6.8, p=0.08; SOAC: 3.0; 95% CI: 1.1, 8.7, p=0.04). There was no association (HR=1.2; 95% CI: 0.5, 2.6, p=0.68) between self-reported arm swelling and OS. Conclusions These findings suggest that lymphedema may influence survival following breast cancer treatment and warrant further investigation in other cancer cohorts and explication of a potential underlying biology.

Does the effect of weight lifting on lymphedema following breast cancer differ by diagnostic method: results from a randomized controlled trial

The lymphedema diagnostic method used in descriptive or intervention studies may influence results found. The purposes of this work were to compare baseline lymphedema prevalence in the physical activity and lymphedema (PAL) trial cohort and to subsequently compare the effect of the weight-lifting intervention on lymphedema, according to four standard diagnostic methods. The PAL trial was a randomized controlled intervention study, involving 295 women who had previously been treated for breast cancer, and evaluated the effect of 12 months of weight lifting on lymphedema status. Four diagnostic methods were used to evaluate lymphedema outcomes: (i) interlimb volume difference through water displacement, (ii) interlimb size difference through sum of arm circumferences, (iii) interlimb impedance ratio using bioimpedance spectroscopy, and (iv) a validated self-report survey. Of the 295 women who participated in the PAL trial, between 22 and 52% were considered to have lymphedema at baseline according to the four diagnostic criteria used. No between-group differences were noted in the proportion of women who had a change in interlimb volume, interlimb size, interlimb ratio, or survey score of ≥5, ≥5, ≥10%, and 1 unit, respectively (cumulative incidence ratio at study end for each measure ranged between 0.6 and 0.8, with confidence intervals spanning 1.0). The variation in proportions of women within the PAL trial considered to have lymphoedema at baseline highlights the potential impact of the diagnostic criteria on population surveillance regarding prevalence of this common morbidity of treatment. Importantly though, progressive weight lifting was shown to be safe for women following breast cancer, even for those at risk or with lymphedema, irrespective of the diagnostic criteria used.