Systematic review of pharmacologic and non-pharmacologic interventions to manage cognitive alterations after chemotherapy for breast cancer

Purpose Cognitive alterations are reported in breast cancer patients receiving chemotherapy. This has adverse effects on patients’ quality of life and function. This systematic review investigates the effectiveness of pharmacologic and non-pharmacologic interventions to manage cognitive alterations associated with breast cancer treatment. Methods Medline via EBSCOhost, CINAHL and Cochrane CENTRAL were searched for the period January 1999 to May 2014 for prospective randomized controlled trials related to the management of chemotherapy-associated cognitive alterations. Included studies investigated the management of chemotherapy-associated cognitive alterations and used subjective or objective measures in patients with breast cancer during or after chemotherapy. Two authors independently extracted data and assessed the risk of bias. Results Thirteen studies involving 1138 participants were included. Overall, the risk of bias for the 13 studies were either high (n=11) or unclear (n=2). Pharmacologic interventions included psychostimulants (n=4), epoetin alfa (n=1), and Ginkgo biloba (n=1). Non-pharmacologic interventions were cognitive training (n=5) and physical activity (n=2). Pharmacologic agents were ineffective except for self-reported cognitive function in an epoetin alfa study. Cognitive training interventions demonstrated benefits in self-reported cognitive function, memory, verbal function and language and orientation/attention. Physical activity interventions were effective in improving executive function and self-reported concentration. Conclusion Current evidence does not favor the pharmacologic management of cognitive alterations associated with breast cancer treatment. Cognitive training and physical activity interventions appear promising, but additional studies are required to establish their efficacy. Further research is needed to overcome methodological shortfalls such as heterogeneity in participant characteristics and non-standardized neuropsychological outcome measures.

Fruit-feeding behaviour and use of olfactory cues by the fruit bat Rousettus leschenaulti: an experimental study

This paper describes the feeding behaviour ofRousettus leschenaulti Desmarest, 1820 on lychees, the preferred cultivated food of this bat in captive conditions. We found that feeding comprised 25–30% of the total activity of these animals in a flight cage and that feeding durations were not significantly different between two sexes. To evaluate the role of odor and vision in foraging behaviour, we provided animals with artificial lychees, real lychees and artificial lychees soaked in the juice of real lychees and we recorded the number of feeding approaches to the different “fruit” types. The results indicated that bats approached real fruit significantly more than artificial fruit, and that the number of approaches to the soaked artificial fruit was also significantly higher than to the unsoaked artificial fruit. There were no significant differences between sexes in approach rates to any “fruit” type. We discuss the role of different sensory cues in the foraging behaviour of these bats and emphasize that the olfactory cue is important in detecting food resources and discriminating between different kinds of food items.

Paternal postnatal depressive symptoms, infant sleeping and feeding behaviors, and rigid parental regulation : a correlational study

Paternal postnatal depression (PND) is now recognized as a serious and prevalent problem, associated with poorer well-being and functioning of all family members. Aspects of infant temperament, sleeping and feeding perceived by parents as problematic are associated with maternal PND, however, less is known about paternal PND. This study investigated depressive symptoms (Edinburgh postnatal depression scale (EPDS)) in 219 fathers of infants aged from 1 to 24 weeks (median 7.0 weeks). Infant predictor variables were sleeping problems, feeding problems and both mother and father reported temperament. Control variables were partner’s support, other support and life events. Rigidity of parenting beliefs regarding infant regulation was also measured as a potential moderating factor. Infant feeding difficulties were associated with paternal depressive symptoms, subsuming the variance associated with both sleep problems and temperament. This relationship was not moderated by regulation beliefs. It was concluded that infant feeding is important to fathers. Fathers of infants with feeding difficulties may not be able to fulfill their idealized construction of involved fatherhood. Role incongruence may have an etiological role in paternal PND.

Parent feeding interactions and practices during childhood cancer treatment: A qualitative investigation

In the general population it is evident that parent feeding practices can directly shape a child’s life long dietary intake. Young children undergoing childhood cancer treatment may experience feeding difficulties and limited food intake, due to the inherent side effects of their anti-cancer treatment. What is not clear is how these treatment side effects are influencing the parent–child feeding relationship during anti-cancer treatment. This retrospective qualitative study collected telephone based interview data from 38 parents of childhood cancer patients who had recently completed cancer treatment (child’s mean age: 6.98 years). Parents described a range of treatment side effects that impacted on their child’s ability to eat, often resulting in weight loss. Sixty-one percent of parents (n = 23) reported high levels of stress in regard to their child’s eating and weight loss during treatment. Parents reported stress, feelings of helplessness, and conflict and/or tension between parent and the child during feeding/eating interactions. Parents described using both positive and negative feeding practices, such as: pressuring their child to eat, threatening the insertion of a nasogastric feeding tube, encouraging the child to eat and providing home cooked meals in hospital. Results indicated that parent stress may lead to the use of coping strategies such as positive or negative feeding practices to entice their child to eat during cancer treatment. Future research is recommended to determine the implication of parent feeding practice on the long term diet quality and food preferences of childhood cancer survivors.

A multimodal physiotherapy programme plus deep water running for improving cancer-related fatigue and quality of life in breast cancer survivors

The aim of the study was to assess the feasibility and effectiveness of aquatic‐based exercise in the form of deep water running ( DWR ) as part of a multimodal physiotherapy programme ( MMPP ) for breast cancer survivors. A controlled clinical trial was conducted in 42 primary breast cancer survivors recruited from community‐based P rimary C are C entres. Patients in the experimental group received a MMPP incorporating DWR , 3 times a week, for an 8‐week period. The control group received a leaflet containing instructions to continue with normal activities. Statistically significant improvements and intergroup effect size were found for the experimental group for P iper F atigue S cale‐ R evised total score ( d = 0.7, P = 0.001), as well as behavioural/severity ( d = 0.6, P = 0.05), affective/meaning ( d = 1.0, P = 0.001) and sensory ( d = 0.3, P = 0.03) domains. Statistically significant differences between the experimental and control groups were also found for general health ( d = 0.5, P < 0.05) and quality of life ( d = 1.3, P < 0.05). All participants attended over 80% of sessions, with no major adverse events reported. The results of this study suggest MMPP incorporating DWR decreases cancer‐related fatigue and improves general health and quality of life in breast cancer survivors. Further, the high level of adherence and lack of adverse events indicate such a programme is safe and feasible.

Association of the SNP rs2623047 in the HSPG modification enzyme SULF1 with an Australian Caucasian Breast Cancer Cohort

Breast cancer is the second most common cancer worldwide and the most common cancer reported in women. This malignant tumour is characterised by a number of specific features including uncontrolled cell proliferation. It ranks fifth in the world as a cause of cancer death in women. Early diagnosis increases 5 year survival rates up to 95%. Heparan sulfate proteoglycans (HSPGs) are complex proteins composed of a core protein to which a number of highly sulfated side chains are synthesised by a highly co-ordinated process resulting in distinct sulfation patterns, which determine specific interations with cell-signaling partners including growth factors, their receptors, ligands and morphogens. The enzymes responsible for chain initiation, elongation and sulfation are critical for creating HS chain variability conferring biological functionality. This study investigated single nucleotide polymorphism in SULF1, the enzyme responsible for the 6-0 desulfation of heparan sulfate side chains. We investigated this SNP in an Australian Caucasian case-control breast cancer population and found a significant association between SULF1 and breast cancer at both the allelic and genotypic level (allele, p=0.016; genotype, p=0.032). Our results suggest the res2623047 SNP in SULF1 may impact breast cancer susceptibility. Specifically, the T allele of rs2623047 in SULF1 is associated with a increased risk of developing breast cancer in our cohort. The identification of markers including SULF1 may improve detection of this disease at its earliest stages improving patient treatment and prognosis.

Association of heparan sulfate proteoglycans SDC1 and SDC4 polymorphisms with breast cancer in an Australian Caucasian population

Breast cancer is a common disease in both developing and developed countries with early identification and treatment improving prognosis and survival. Heparan sulfate proteoglycans (HSPGs) are key components of the extracellular matrix (ECM) that mediate cell adhesion, motility, proliferation, invasion and cell signalling. Members of the syndecan family of HSPGs have been identified to be involved in breast cancer progression through their varied interactions with a number of growth factors, ligands and receptors. Specifically, high expression levels of syndecan-1 (SDC1) have been demonstrated in more invasive breast tumours while elevated syndecan-4 (SDC4) levels have been identified to correspond with improved prognosis. With genetic changes in the syndecans and their association with breast cancers plausible, we examined two single nucleotide polymorphisms in SDC1 (rs1131351) and SDC4 (rs67068737) within an Australian Caucasian breast cancer case/control population. No association was found with SDC4 and breast cancer in our population. However, a significant association between SDC1 and breast cancer was identified in both our case/control population and in a replication cohort. When both populations were combined for analysis, this association became more significant (genotype, p = 0.0003; allele, p = 0.0001). This data suggests an increased risk of developing breast cancer associated with the presence of the C allele of the SDC1 rs1131351 single nucleotide polymorphism (SNP) and may provide a marker toward early breast cancer detection.

Weight and weight change following breast cancer : evidence from a prospective, population-based, breast cancer cohort study

Background: While weight gain following breast cancer is considered common, results supporting these findings are dated. This work describes changes in body weight following breast cancer over 72 months, compares weight with normative data and explores whether weight changes over time are associated with personal, diagnostic, treatment or behavioral characteristics. Methods: A population-based sample of 287 Australian women diagnosed with early-stage invasive breast cancer was assessed prospectively at six, 12, 18 and 72 months post-surgery. Weight was clinically measured and linear mixed models were used to explore associations between weight and participant characteristics (collected via self-administered questionnaire). Those with BMI changes of one or more units were considered to have experienced clinically significant changes in weight. Results: More than half (57%) of participants were overweight or obese at 6 months post-surgery, and by 72 months post-surgery 68% of women were overweight or obese. Among those who gained more weight than age-matched norms, clinically significant weight gain between 6 and 18 months and 6 and 72 months post-surgery was observed in 24% and 39% of participants, respectively (median [range] weight gain: 3.9kg [2.0-11.3kg] and 5.2kg [0.6-28.7], respectively). Clinically-significant weight losses were observed in up to 24% of the sample (median [range] weight loss between 6 and 72 months post-surgery: -6.4kg [-1.9--24.6kg]). More extensive lymph node removal, being treated on the non-dominant side, receiving radiation therapy and lower physical activity levels at 6 months was associated with higher body weights post-breast cancer (group differences >3kg; all p<0.05). Conclusions: While average weight gain among breast cancer survivors in the long-term is small, subgroups of women experience greater gains linked with adverse health and above that experienced by age-matched counterparts. Weight change post-breast cancer is a contemporary public health issue and the integration of healthy weight education and support into standard breast cancer care has potential to significantly improve the length and quality of cancer survivorship.

Facilitating lifestyle changes to manage menopausal symptoms in women with breast cancer: A randomized controlled pilot trial of The Pink Women’s Wellness Program

OBJECTIVE Women diagnosed as having breast cancer may experience difficulties with posttreatment effects such as menopausal symptoms. The aims of this pilot study were to (1) evaluate the impact of a multimodal lifestyle program on reducing menopausal symptoms in women with breast cancer and (2) examine the impact of the program on health-related quality of life (HRQoL) and adherence to lifestyle recommendations. METHODS Overall, 55 women aged 45 to 60 years with one moderate to severe menopausal symptom and a history of breast cancer were randomized into an intervention group (n = 26) or a control group (n = 29). Women in the intervention group received a lifestyle intervention (The Pink Women’s Wellness Program) that included clinical consultations and a tailored health education program. Measurements of menopausal symptoms (Greene Climacteric Scale), HRQoL (SF-12 and Functional Assessment of Cancer Therapy—Breast), and modifiable lifestyle factors (food intake, physical activity, smoking and alcohol use, and sleep disturbance) were taken at baseline and 12 weeks. RESULTS Women in the intervention group reported clinically significant reductions in many menopausal symptoms, specifically somatic symptoms (d = 0.52), vasomotor symptoms (d = 0.55), sexual dysfunction (d = .65), and overall menopausal symptoms (d = 0.54), at 12 weeks compared with the control group (d = 0.03, d = 0.24, d = 0.18, and d = 0.05, respectively). Women in the intervention group reported improvements in Functional Assessment of Cancer Therapy—Breast subscale scores, physical well-being and functional well-being, and Functional Assessment of Cancer Therapy—General total scores (intervention group: d = 0.54, d = 0.50, and d = 0.48, respectively; control group: d = 0.22, d = 0.11, and d = 0.05, respectively). CONCLUSIONS The Pink Women’s Wellness Program is effective in decreasing menopausal symptoms, thus improving HRQoL. This being a pilot study, further research is recommended to investigate the benefits of combining nonpharmacological interventions for women with breast cancer to reduce their treatment-related menopausal symptoms.

Developing a three-dimensional in-vitro cell culture model for studying breast and prostate cancer using starPEG-heparin hydrogels

Introduction Hydrogels prepared from poly(ethylene glycol) (PEG) and maleimide-functionalized heparin provide a potential matrix for use in developing three dimensional (3D) models. We have previously demonstrated that these hydrogels support the cultivation of human umbilical vein endothelial cells (HUVECs) (1). We extend this body of work to study the ability to create an extracellular matrix (ECM)-like model to study breast and prostate cancer cell growth in 3D. Also, we investigate the ability to produce a tri-culture mimicking tumour angiogenesis with cancer spheroids, HUVECs and mesenchymal stem cells (MSC). Materials and Methods The breast cancer cell lines, MCF-7 and MDA-MB-231, and prostate cancer cell lines, LNCaP and PC3, were seeded into starPEG-heparin hydrogels and grown for 14 Days to analyse the effects of varying hydrogel stiffness on spheroid development. Resulting hydrogel constructs were analyzed via Alamar Blue assays, light microscopy, and immunofluorescence staining for cytokeratin 8/18, Ki67 and E-Cadherin. Cancer cell lines were then pre-grown in hydrogels for 5-7 days and then re-seeded into starPEG-heparin hydrogels functionalised with RGD, SDF-1, bFGF and VEGF as spheroids with HUVECs and MSC and grown for 14 days as a tri-culture in Endothelial Cell Growth Medium (ECGM; Promocell). Cell lines were also seeded as a single cell suspension into the functionalised tri-culture system. Cultures were fixed in 4% paraformaldehyde and analysed via immunostaining for Von Willebrand Factor and CD31, as well as the above mentioned markers, and observed using confocal microscopy. Results Cultures prepared in MMP-cleavable starPEG-heparin hydrogels display spheroid formation in contrast to adherent growth on tissue culture plastic. Small differences were visualised in cancer spheroid growth between different gel stiffness across the range of cell lines. Cancer cell lines were able to be co-cultivated with HUVECs and MSC. HUVEC tube formation and cancer line spheroid formation occured after 3-4 days. Interaction was visualised between tumours and HUVECs via confocal microscopy. Slightly increased interaction was seen between cancer tumours and micro-vascular tubes when seeded as single cells compared with the pre-formed spheroid approach. Further studies intend to utilise cytokine gradients to further optimise the ECM environment of in situ tumour angiogenesis. Discussion and Conclusions Our results confirm the suitability of hydrogels constructed from starPEG-heparin for HUVECs and MSC co-cultivation with cancer cell lines to study cell-cell and cell-matrix interactions in a 3D environment. This represents a step forward in the development of 3D culture models to study the pathomechanisms of breast and prostate cancer. References 1. Tsurkan MV, Chwalek K, Prokoph S, Zieris A, Levental KR, Freudenberg U, Werner C. Advanced Materials. 25, 2606-10, 2013. Disclosures The authors declare no conflicts of interest

Relationships between maternal overweight prior to pregnancy, feeding mode and infant feeding beliefs and practices

Aim To examine whether pre-pregnancy weight status was associated with maternal feeding beliefs and practices in the early post-partum period. Methods Secondary analysis of longitudinal data from Australian mothers. Participants (N=486) were divided into two weight status groups based on self-reported pre-pregnancy weight and measured height: healthy weight (BMI <25kg/m2; n=321) and overweight (BMI>25kg/m2; n=165). Feeding beliefs and practices were self-reported via an established questionnaire that assessed concerns about infant overeating and undereating, awareness of infant cues, feeding to a schedule, and using food to calm. Results Infants of overweight mothers were more likely to have been given solid foods in the previous 24hrs (29% vs 20%) and fewer were fully breastfed (50% vs 64%). Multivariable regression analyses (adjusted for maternal education, parity, average infant weekly weight gain, feeding mode and introduction of solids) revealed pre-pregnancy weight status was not associated with using food to calm, concern about undereating, awareness of infant cues or feeding to a schedule. However feeding mode was associated with feeding beliefs and practices. Conclusions Although no evidence for a relationship between maternal weight status and early maternal feeding beliefs and practices was observed, differences in feeding mode and early introduction of solids was observed. The emergence of a relationship between feeding practices and maternal weight status may occur when the children are older, solid feeding is established and they become more independent in feeding.

The relationship between controlling feeding practices and boys’ and girls’ eating in the absence of hunger

Parental controlling feeding practices have been directly associated with maladaptive child eating behaviours, such as Eating in the Absence of Hunger (EAH). The aim of this study was to examine EAH in very young children (3-4 years old) and to investigate the association between maternal controlling feeding practices and energy intake from a standardised selection of snacks consumed ‘in the absence of hunger’. Thirty-seven mother-child dyads enrolled in the NOURISH RCT participated in a modified EAH protocol conducted in the child’s home. All children displayed EAH, despite 80% reporting to be full or very full following completion of lunch 15 minutes earlier. The relationship between maternal and child covariates and controlling feeding practices and EAH were examined using non-parametric tests, and were stratified by child gender. For boys only, pressure to eat was positively associated with EAH. Neither restriction nor monitoring practices were associated with EAH in either boys or girls. Overall, the present findings suggest gender differences in the relationship between maternal feeding practices and children’s eating behaviours emerge early and should be considered in future research and intervention design.

In vitro microenvironments to study breast cancer bone colonisation

Bone metastasis occurs frequently in patients with advanced breast cancer and is a major cause of morbidity and mortality in these patients. In order to advance current therapies, the mechanisms leading to the formation of bone metastases and their pathophysiology have to be better understood. Several in vitro models have been developed for systematic studies of interactions between breast cancer cells and the bone microenvironment. Such models can provide insights into the molecular basis of bone metastatic colonisation and also may provide a useful platform to design more physiologically relevant drug testing assays. This review describes different in vitro approaches and discusses their advantages and disadvantages.

An early feeding practices intervention for obesity prevention

Objective - Report long term outcomes of the NOURISH randomized controlled trial (RCT) that evaluated a universal intervention commencing in infancy to provide anticipatory guidance to first-time mothers on ‘protective’ complementary feeding practices which were hypothesized to reduce childhood obesity risk. Subjects and Methods - The NOURISH RCT enrolled 698 mothers (mean age 30.1 years, SD=5.3) with healthy term infants (51% female). Mothers were randomly allocated to usual care or to attend two 6-session, 12-week group education modules. Outcomes were assessed five times: baseline (infants 4.3 months); 6 months after module 1 (infants 14 months); 6 months after module 2 (infants 2 years) and at 3.5 and 5 years of age. Maternal feeding practices were self-reported using validated questionnaires. BMI Z-score was calculated from measured child height and weight. Linear Mixed Models evaluated intervention (group) effect across time. Results - Retention at 5 years of age was 61%. Across ages 2-5 years, intervention mothers reported less frequent use of non-responsive feeding practices on 6/9 scales. At 5 years they also reported more appropriate responses to food refusal on 7/12 items (Ps ≤.05). No statistically significant group effect was noted for anthropometric outcomes (BMI Z-score: P=.06), or the prevalence of overweight/obesity (control 13.3% vs. intervention 11.4%, P=.66). Conclusions - Anticipatory guidance on complementary feeding resulted in first-time mothers reporting increased use of protective feeding practices. These intervention effects were sustained up to five years of age and were paralleled by a non-significant trend for lower child BMI Z-scores at all post-intervention assessment points.