Does quality of life among breast cancer survivors one year after diagnosis differ depending on urban and non-urban residence? A comparative study

Background: This study examined the quality of life (QOL), measured by the Functional Assessment of Cancer Therapy (FACT) questionnaire, among urban (n=277) and non-urban (n=323) breast cancer survivors and women from the general population (n=1140) in Queensland, Australia. ---------- Methods: Population-based samples of breast cancer survivors aged <75 years who were 12 months post-diagnosis and similarly-aged women from the general population were recruited between 2002 and 2007. ---------- Results: Age-adjusted QOL among urban and non-urban breast cancer survivors was similar, although QOL related to breast cancer concerns was the weakest domain and was lower among non-urban survivors than their urban counterparts (36.8 versus 40.4, P<0.01). Irrespective of residence, breast cancer survivors, on average, reported comparable scores on most QOL scales as their general population peers, although physical well-being was significantly lower among non-urban survivors (versus the general population, P<0.01). Overall, around 20%-33% of survivors experienced lower QOL than peers without the disease. The odds of reporting QOL below normative levels were increased more than two-fold for those who experienced complications following surgery, reported upper-body problems, had higher perceived stress levels and/or a poor perception of handling stress (P<0.01 for all). ---------- Conclusions: Results can be used to identify subgroups of women at risk of low QOL and to inform components of tailored recovery interventions to optimize QOL for these women following cancer treatment.

Patterns, correlates, and prognostic significance of quality of life following breast cancer

Objective To describe quality of life (QOL) over a 12-month period among women with breast cancer, consider the association between QOL and overall survival (OS), and explore characteristics associated with QOL declines. Methods A population-based sample of Australian women (n=287) with invasive, unilateral breast cancer (Stage I+), was observed prospectively for a median of 6.6 years. QOL was assessed at six, 12 and 18 months post-diagnosis, using the Functional Assessment of Cancer Therapy, Breast (FACT-B+4) questionnaire. Raw scores for the FACT-B+4 and subscales were computed and individuals were categorized according to whether QOL declined, remained stable or improved between six and 18 months. Kaplan-Meier and Cox proportional hazards survival methods were used to estimate OS and its associations with QOL. Logistic regression models identified factors associated with QOL decline. Results Within FACT-B+4 sub-scales, between 10% and 23% of women showed declines in QOL. Following adjustment for established prognostic factors, emotional wellbeing and FACT-B+4 scores at six months post-diagnosis were associated with OS (p<0.05). Declines in physical (p<0.01) or functional (p=0.02) well-being between six and 18 months post-diagnosis were also associated significantly with OS. Receiving multiple forms of adjuvant treatment, a perception of not handling stress well and reporting one or more other major life events at six months post-diagnosis were factors associated with declines in QOL in multivariable analyses. Conclusions Interventions targeted at preventing QOL declines may ultimately improve quantity as well as quality of life following breast cancer.

Upper-body morbidity following breast cancer treatment is common, may persist longer-term and adversely influences quality of life

Background: Impairments in upper-body function (UBF) are common following breast cancer. However, the relationship between arm morbidity and quality of life (QoL) remains unclear. This investigation uses longitudinal data to describe UBF in a population-based sample of women with breast cancer and examines its relationship with QoL. ---------- Methods: Australian women (n = 287) with unilateral breast cancer were assessed at three-monthly intervals, from six- to 18-months post-surgery (PS). Strength, endurance and flexibility were used to assess objective UBF, while the Disability of the Arm, Shoulder and Hand questionnaire and the Functional Assessment of Cancer Therapy- Breast questionnaire were used to assess self-reported UBF and QoL, respectively. ---------- Results: Although mean UBF improved over time, up to 41% of women revealed declines in UBF between sixand 18-months PS. Older age, lower socioeconomic position, treatment on the dominant side, mastectomy, more extensive lymph node removal and having lymphoedema each increased odds of declines in UBF by at least twofold (p < 0.05). Lower baseline and declines in perceived UBF between six- and 18-months PS were each associated with poorer QoL at 18-months PS (p < 0.05). ---------- Conclusions: Significant upper-body morbidity is experienced by many following breast cancer treatment, persisting longer term, and adversely influencing the QoL of breast cancer survivors.

Prevalence of upper-body symptoms following breast cancer and its relationship with upper-body function and lymphoedema

This investigation describes the prevalence of upper-body symptoms in a population-based sample of women with breast cancer (BC) and examines their relationships with upper-body function (UBF) and lymphoedema, as two clinically important sequelae. Australian women (n=287) with unilateral BC were assessed at three-monthly intervals, from six to 18 months post-surgery (PS). Participants reported the presence and intensity of upper-body symptoms on the treated side. Objective and self-reported UBF and lymphoedema (bioimpedance spectroscopy) were also assessed. Approximately 50% of women reported at least one moderate-to-extreme symptom at 6- and at 18-months PS. There was a significant relationship between symptoms and function (p<0.01), whereby perceived and objective function declined with increasing number of symptoms present. Those with lymphoedema were more likely to report multiple symptoms and presence of symptoms at baseline increased risk of lymphoedema (ORs>1.3, p=0.02). Although, presence of symptoms explained only 5.5% of the variation in the odds of lymphoedema. Upper-body symptoms are common and persistent following breast cancer and are associated with clinical ramifications, including reduced UBF and increased risk of developing lymphoedema. However, using the presence of symptoms as a diagnostic indicator of lymphoedema is limited.

Accelerated Partial Breast Irradiation (APBI) : a review of available techniques

Breast conservation therapy (BCT) is the procedure of choice for the management of the early stage breast cancer. However, its utilization has not been maximized because of logistics issues associated with the protracted treatment involved with the radiation treatment. Accelerated Partial Breast Irradiation (APBI) is an approach that treats only the lumpectomy bed plus a 1-2 cm margin, rather than the whole breast. Hence because of the small volume of irradiation a higher dose can be delivered in a shorter period of time. There has been growing interest for APBI and various approaches have been developed under phase I-III clinical studies; these include multicatheter interstitial brachytherapy, balloon catheter brachytherapy, conformal external beam radiation therapy and intra-operative radiation therapy (IORT). Balloon-based brachytherapy approaches include Mammosite, Axxent electronic brachytherapy and Contura, Hybrid brachytherapy devices include SAVI and ClearPath. This paper reviews the different techniques, identifying the weaknesses and strength of each approach and proposes a direction for future research and development. It is evident that APBI will play a role in the management of a selected group of early breast cancer. However, the relative role of the different techniques is yet to be clearly identified.

Migration of breast cancer cells : understanding the roles of volume exclusion and cell-to-cell adhesion

We study MCF-7 breast cancer cell movement in a transwell apparatus. Various experimental conditions lead to a variety of monotone and nonmonotone responses which are difficult to interpret. We anticipate that the experimental results could be caused by cell-to-cell adhesion or volume exclusion. Without any modeling, it is impossible to understand the relative roles played by these two mechanisms. A lattice-based exclusion process random-walk model incorporating agent-to-agent adhesion is applied to the experimental system. Our combined experimental and modeling approach shows that a low value of cell-to-cell adhesion strength provides the best explanation of the experimental data suggesting that volume exclusion plays a more important role than cell-to-cell adhesion. This combined experimental and modeling study gives insight into the cell-level details and design of transwell assays.

Prevalence and determinants of the health promotion and risk reduction practices of younger female survivors of breast cancer

This thesis describes a discrete component of a larger mixed-method (survey and interview) study that explored the health-promotion and risk-reduction practices of younger premenopausal survivors of ovarian, breast and haematological cancers. This thesis outlines my distinct contribution to the larger study, which was to: (1) Produce a literature review that thoroughly explored all longer-term breast cancer treatment outcomes, and which outlined the health risks to survivors associated with these; (2) Describe and analyse the health-promotion and risk-reduction behaviours of nine younger female survivors of breast cancer as articulated in the qualitative interview dataset; and (3) Test the explanatory power of the Precede-Proceed theoretical framework underpinning the study in relation to the qualitative data from the breast cancer cohort. The thesis reveals that breast cancer survivors experienced many adverse outcomes as a result of treatment. While they generally engaged in healthy lifestyle practices, a lack of knowledge about many recommended health behaviours emerged throughout the interviews. The participants also described significant internal and external pressures to behave in certain ways because of the social norms surrounding the disease. This thesis also reports that the Precede-Proceed model is a generally robust approach to data collection, analysis and interpretation in the context of breast cancer survivorship. It provided plausible explanations for much of the data in this study. However, profound sociological and psychological implications arose during the analysis that were not effectively captured or explained by the theories underpinning the model. A sociological filter—such as Turner’s explanation of the meaning of the body and embodiment in the social sphere (Turner, 2008)—and the psychological concerns teased out in Mishel’s (1990) Uncertainty in Illness Theory, provided a useful dimension to the findings generated through the Precede-Proceed model. The thesis concludes with several recommendations for future research, clinical practice and education in this context.

Factors influencing quality of life in patients with benign primary brain tumors : prior to and following surgery

Goals: Few studies have repeatedly evaluated quality of life and potentially relevant factors in patients with benign primary brain tumor. The purpose of this study was to explore the relationship between the experience of the symptom distress, functional status, depression, and quality of life prior to surgery (T1) and 1 month post-discharge (T2). ---------- Patients and methods: This was a prospective cohort study including 58 patients with benign primary brain tumor in one teaching hospital in the Taipei area of Taiwan. The research instruments included the M.D. Anderson Symptom Inventory, the Functional Independence Measure scale, the Hospital Depression Scale, and the Functional Assessment of Cancer Therapy-Brain.---------- Results: Symptom distress (T1: r=−0.90, p<0.01; T2: r=−0.52, p<0.01), functional status (T1: r=0.56, p<0.01), and depression (T1: r=−0.71, p<0.01) demonstrated a significant relationship with patients' quality of life. Multivariate analysis identified symptom distress (explained 80.2%, Rinc 2=0.802, p=0.001) and depression (explained 5.2%, Rinc 2=0.052, p<0.001) continued to have a significant independent influence on quality of life prior to surgery (T1) after controlling for key demographic and medical variables. Furthermore, only symptom distress (explained 27.1%, Rinc 2=0.271, p=0.001) continued to have a significant independent influence on quality of life at 1 month after discharge (T2).---------- Conclusions: The study highlights the potential importance of a patient's symptom distress on quality of life prior to and following surgery. Health professionals should inquire about symptom distress over time. Specific interventions for symptoms may improve the symptom impact on quality of life. Additional studies should evaluate symptom distress on longer-term quality of life of patients with benign brain tumor.

Insulin-like growth factor-i : vitronectin complex-induced changes in gene expression effect breast cell survival and migration

Recent studies have demonstrated that IGF-I associates with VN through IGF-binding proteins (IGFBP) which in turn modulate IGF-stimulated biological functions such as cell proliferation, attachment and migration. Since IGFs play important roles in transformation and progression of breast tumours, we aimed to describe the effects of IGF-I:IGFBP:VN complexes on breast cell function and to dissect mechanisms underlying these responses. In this study we demonstrate that substrate-bound IGF-I:IGFBP:VN complexes are potent stimulators of MCF-7 breast cell survival, which is mediated by a transient activation of ERK/MAPK and sustained activation of PI3-K/AKT pathways. Furthermore, use of pharmacological inhibitors of the MAPK and PI3-K pathways confirms that both pathways are involved in IGF-I:IGFBP:VN complex-mediated increased cell survival. Microarray analysis of cells stimulated to migrate in response to IGF-I:IGFBP:VN complexes identified differential expression of genes with previously reported roles in migration, invasion and survival (Ephrin-B2, Sharp-2, Tissue-factor, Stratifin, PAI-1, IRS-1). These changes were not detected when the IGF-I analogue (\[L24]\[A31]-IGF-I), which fails to bind to the IGF-I receptor, was substituted; confirming the IGF-I-dependent differential expression of genes associated with enhanced cell migration. Taken together, these studies have established that IGF-I:IGFBP:VN complexes enhance breast cell migration and survival, processes central to facilitating metastasis. This study highlights the interdependence of ECM and growth factor interactions in biological functions critical for metastasis and identifies potential novel therapeutic targets directed at preventing breast cancer progression.

Low frequency of CHEK2 1100delC allele in Australian multiple-case breast cancer families : functional analysis in heterozygous individuals

A protein-truncating variant of CHEK2, 1100delC, is associated with a moderate increase in breast cancer risk. We have determined the prevalence of this allele in index cases from 300 Australian multiple-case breast cancer families, 95% of which had been found to be negative for mutations in BRCA1 and BRCA2. Only two (0.6%) index cases heterozygous for the CHEK2 mutation were identified. All available relatives in these two families were genotyped, but there was no evidence of co-segregation between the CHEK2 variant and breast cancer. Lymphoblastoid cell lines established from a heterozygous carrier contained approximately 20% of the CHEK2 1100delC mRNA relative to wild-type CHEK2 transcript. However, no truncated CHK2 protein was detectable. Analyses of expression and phosphorylation of wild-type CHK2 suggest that the variant is likely to act by haploinsufficiency. Analysis of CDC25A degradation, a downstream target of CHK2, suggests that some compensation occurs to allow normal degradation of CDC25A. Such compensation of the 1100delC defect in CHEK2 might explain the rather low breast cancer risk associated with the CHEK2 variant, compared to that associated with truncating mutations in BRCA1 or BRCA2.

Design and implementation of the Exercise for Health trial – a pragmatic exercise intervention for women with breast cancer

Background Exercise for Health was a pragmatic, randomised, controlled trial comparing the effect of an eight-month exercise intervention on function, treatment-related side effects and quality of life following breast cancer, compared with usual care. The intervention commenced six weeks post-surgery, and two modes of delivering the same intervention was compared with usual care. The purpose of this paper is to describe the study design, along with outcomes related to recruitment, retention and representativeness, and intervention participation. Methods: Women newly diagnosed with breast cancer and residing in a major metropolitan city of Queensland, Australia, were eligible to participate. Consenting women were randomised to a face-to-face-delivered exercise group (FtF, n=67), telephone-delivered exercise group (Tel, n=67) or usual care group (UC, n=60) and were assessed pre-intervention (5-weeks post-surgery), mid-intervention (6 months post-surgery) and 10 weeks post-intervention (12 months post-surgery). Each intervention arm entailed 16 sessions with an Exercise Physiologist. Results: Of 318 potentially eligible women, 63% (n=200) agreed to participate, with a 12-month retention rate of 93%. Participants were similar to the Queensland breast cancer population with respect to disease characteristics, and the randomisation procedure was mostly successful at attaining group balance, with the few minor imbalances observed unlikely to influence intervention effects given balance in other related characteristics. Median participation was 14 (min, max: 0, 16) and 13 (min, max: 3, 16) intervention sessions for the FtF and Tel, respectively, with 68% of those in Tel and 82% in FtF participating in at least 75% of sessions. Discussion: Participation in both intervention arms during and following treatment for breast cancer was feasible and acceptable to women. Future work, designed to inform translation into practice, will evaluate the quality of life, clinical, psychosocial and behavioural outcomes associated with each mode of delivery.

Comparison of standard image segmentation methods for segmentation of brain tumors from 2D MR images

In the analysis of medical images for computer-aided diagnosis and therapy, segmentation is often required as a preliminary step. Medical image segmentation is a complex and challenging task due to the complex nature of the images. The brain has a particularly complicated structure and its precise segmentation is very important for detecting tumors, edema, and necrotic tissues in order to prescribe appropriate therapy. Magnetic Resonance Imaging is an important diagnostic imaging technique utilized for early detection of abnormal changes in tissues and organs. It possesses good contrast resolution for different tissues and is, thus, preferred over Computerized Tomography for brain study. Therefore, the majority of research in medical image segmentation concerns MR images. As the core juncture of this research a set of MR images have been segmented using standard image segmentation techniques to isolate a brain tumor from the other regions of the brain. Subsequently the resultant images from the different segmentation techniques were compared with each other and analyzed by professional radiologists to find the segmentation technique which is the most accurate. Experimental results show that the Otsu’s thresholding method is the most suitable image segmentation method to segment a brain tumor from a Magnetic Resonance Image.