Treatment intervals and survival for women diagnosed with early breast cancer in Queensland: the Breast Cancer Outcomes Study, a population-based cohort study.

OBJECTIVES: To assess associations between breast cancer-specific survival and timeliness of treatment, based on 2020 Australian guidelines for the treatment of early breast cancer. DESIGN: Population-based cohort study; analysis of linked Queensland Cancer Register, patient medical record, and National Death Index data, supplemented by telephone interviews. SETTING, PARTICIPANTS: Women aged 20-79 years diagnosed with invasive breast cancer during 1 March 2010 - 30 June 2013, followed to 31 December 2020. MAIN OUTCOME MEASURES: Breast cancer-specific survival for women who received or did not receive treatment within the recommended timeframe, overall and for six treatment intervals; optimal cut-points for each treatment interval; characteristics of women for whom treatment was not provided within the recommended timeframe. RESULTS: Of 5426 eligible women, 4762 could be invited for interviews; complete data were available for 3044 women (56% of eligible women, 65% of invited women). Incomplete compliance with guideline interval recommendations was identified for 1375 women (45%); their risk of death from breast cancer during the follow-up period was greater than for those for whom guideline compliance was complete (adjusted hazard ratio [aHR], 1.43; 95% confidence interval [CI], 1.04-1.96). Risk of death was greater for women for whom the diagnosis to surgery interval exceeded 29 days (aHR, 1.76; 95% CI, 1.19-2.59), the surgery to chemotherapy interval exceeded 36 days (aHR, 1.63; 95% CI, 1.13-2.36), or the chemotherapy to radiotherapy interval exceeded 31 days (aHR, 1.83; 95% CI, 1.19-2.80). Treatment intervals longer than recommended were more frequent for women for whom breast cancer was detected by public facility screening (adjusted odds ratio [aOR], 1.58; 95% CI, 1.22-2.04) or by symptoms (aOR, 1.39; 95% CI, 1.09-1.79) than when cancer had been detected in private facilities, and for women without private health insurance (aOR, 1.96; 95% CI, 1.66-2.32) or living outside major cities (aOR, 1.38; 95% CI, 1.18-1.62). CONCLUSIONS: Breast cancer-specific survival was poorer for women for whom the diagnosis to surgery, surgery to chemotherapy, or chemotherapy to radiotherapy intervals exceeded guideline-recommended limits. Our findings support 2020 Australian guideline recommendations regarding timely care.

"Everyone needs a Deb": what Australian indigenous women say about breast cancer screening and treatment services.

BACKGROUND: Breast cancer continues to be the second most diagnosed cancer overall and the most diagnosed cancer for women in Australia. While mortality rates overall have declined in recent years, Indigenous women continue to be diagnosed at more marginal rates (0.9 times) and are more likely to die (1.2 times). The literature provides a myriad of reasons for this; however, the voices of Indigenous women are largely absent. This study sets out to understand what is happening from the perspectives of Australian Indigenous women with a view to charting culturally safer pathways that improve participation in screening and treatment by Indigenous women. METHODS: This co-design study was conducted using semi-structured, in-depth interviews and focus group discussions. Recruitment of study participants was via snowball sampling. Participants were subsequently consented into the study through the Aboriginal Health Service and the research team. Interviews were audio recorded and transcribed verbatim, and data coded in NVivo12 using inductive thematic analysis. RESULTS: A total of 21 Indigenous women and 14 health service providers were interviewed predominantly from the same regional/rural area in NSW, with a small proportion from other states in Australia. Six major themes were identified: Access, Awareness, Community and Family, Lack of control, Negative feelings and associations and Role of services. CONCLUSION: To improve access and participation of Indigenous women and ultimately improve mortality rates, breast cancer services must explicitly address cultural and community needs.

GelMA, Click-Chemistry Gelatin and Bioprinted Polyethylene Glycol-Based Hydrogels as 3D Ex Vivo Drug Testing Platforms for Patient-Derived Breast Cancer Organoids.

3D organoid model technologies have led to the development of innovative tools for cancer precision medicine. Yet, the gold standard culture system (Matrigel®) lacks the ability for extensive biophysical manipulation needed to model various cancer microenvironments and has inherent batch-to-batch variability. Tunable hydrogel matrices provide enhanced capability for drug testing in breast cancer (BCa), by better mimicking key physicochemical characteristics of this disease's extracellular matrix. Here, we encapsulated patient-derived breast cancer cells in bioprinted polyethylene glycol-derived hydrogels (PEG), functionalized with adhesion peptides (RGD, GFOGER and DYIGSR) and gelatin-derived hydrogels (gelatin methacryloyl; GelMA and thiolated-gelatin crosslinked with PEG-4MAL; GelSH). Within ranges of BCa stiffnesses (1−6 kPa), GelMA, GelSH and PEG-based hydrogels successfully supported the growth and organoid formation of HR+,−/HER2+,− primary cancer cells for at least 2−3 weeks, with superior organoid formation within the GelSH biomaterial (up to 268% growth after 15 days). BCa organoids responded to doxorubicin, EP31670 and paclitaxel treatments with increased IC50 concentrations on organoids compared to 2D cultures, and highest IC50 for organoids in GelSH. Cell viability after doxorubicin treatment (1 µM) remained >2-fold higher in the 3D gels compared to 2D and doxorubicin/paclitaxel (both 5 µM) were ~2.75−3-fold less potent in GelSH compared to PEG hydrogels. The data demonstrate the potential of hydrogel matrices as easy-to-use and effective preclinical tools for therapy assessment in patient-derived breast cancer organoids.

A cost-consequences analysis of the SAFE trial: a comparative, effectiveness trial evaluating high- versus low-supervision of an exercise intervention for women with breast cancer.

PURPOSE: The aim of this analysis was to compare the cost-consequences of a 12 week exercise intervention when delivered under high- versus low-level supervision conditions by an Exercise Professional (ExP) to women with breast cancer. METHODS: 60 women (50 ± 9 years) with stage II + breast cancer, who were insufficiently active, and reported ≥ 1 comorbidities or persistent treatment-related side-effects, were randomized to the high- or low-supervision group. The high-supervision group received 20 supervised sessions with an ExP over a 12 week period (reflecting a typical research model), whereas the low-supervision group received five sessions over the same period (replicating what is publicly funded within Australia). Health outcomes including health-related quality of life, and physical and psychosocial outcomes were assessed at baseline and post-intervention. To assess intervention consequences, composite effectiveness scores were created by calculating mean z-scores from raw data for all outcomes per participant. Total program costs were calculated including program development, staff training, program implementation, and equipment. RESULTS: 79.3% of the high- and 63.0% of the low-supervision group showed clinically relevant health improvements. Cost per improver was $1,814 for 23 improvers and $1,571 for 17 improvers in the high- and low-supervision groups, respectively. CONCLUSION: The SAFE exercise intervention, when delivered via high- or low-supervised conditions, represents good value with over 60% of women in both groups reporting health improvements. High-supervision levels resulted in a greater proportion of women experiencing health benefits, but future research will need to determine the longer term health impacts of these group differences.

A Randomised, Comparative, Effectiveness Trial Evaluating Low- versus High-Level Supervision of an Exercise Intervention for Women with Breast Cancer: The SAFE Trial.

The aim of this comparative, effectiveness trial was to evaluate the safety, feasibility and effect of an exercise intervention delivered via low-level versus high-level supervision. The target population were women who were diagnosed with ≥stage II breast cancer, had ≥ one comorbidity and/or persistent treatment-related side-effects, and were insufficiently physically active. Sixty women (50 ± 9 years) were randomized to the low-supervision group (n = 30) or high-supervision group (n = 30). The low-supervision group participated in a 12-week, individually-tailored exercise intervention supported by five supervised sessions with an exercise professional. The high-supervision group participated in the same exercise intervention but received 20 supervised sessions across the 12-week period. The target weekly dosage of 600 metabolic equivalent minutes of exercise per week (MET-mins/wk) and the session content, such as safety and behaviour change topics, were standardized between the groups. The primary outcomes were intervention safety, defined as the number, type, and severity of exercise-related adverse events (e.g., musculoskeletal injury or exacerbated treatment-related side effects), and feasibility, which was defined as compliance to target exercise dosage. The effect of the intervention on quality of life, physical activity, self-efficacy, fitness, and strength was also assessed (pre- and post-intervention, and at 12-week follow-up). The intervention was safe, with no exercise-related adverse events of grade 3 or above in either group. Both groups reported high compliance to the target exercise dosage (median MET-mins/wk: High = 817; Low = 663), suggesting the exercise intervention was feasible, irrespective of supervision level. Improvements in quality of life, physical activity and fitness were observed post-intervention and maintained at follow-up for both groups (p < 0.05). Only the high-supervision group showed clinically-relevant improvements in strength and self-efficacy at post-intervention (p < 0.05). Individually-targeted exercise delivered under high- or low-levels of supervision is safe, feasible and beneficial for women with stage II+ breast cancer. Future research needs to assess whether the greater gains observed in the group who received higher supervision may contribute to longer term maintenance of physical activity levels and overall health benefits. Australian and New Zealand Clinical Trials Registry: ACTRN12616000547448.

Improving breast cancer outcomes for Aboriginal women: a mixed-methods study protocol.

INTRODUCTION: Breast cancer is the most commonly diagnosed cancer affecting Australian women, and the second highest cause of cancer death in Australian women. While the incidence of breast cancer is lower in Aboriginal women than non-Aboriginal women, the mortality rate for Aboriginal women is higher, with Aboriginal women 1.2 times more likely to die from the disease. In New South Wales, Aboriginal women are 69% more likely to die from their breast cancer than non-Aboriginal women.Co-design is a research method recognised to enhance collaboration between those doing the research and those impacted by the research; which when used with Aboriginal communities, ensures research and services are relevant, culturally competent and empowers communities as co-researchers. We report the development of a new protocol using co-design methods to improve breast cancer outcomes for Aboriginal women. METHODS AND ANALYSIS: Through a Community Mapping Project in 2018, we co-designed an iterative quantitative and qualitative study consisting of five phases. In Phase 1, we will establish a governance framework. In Phase 2, we will provide information to community members regarding the modified parts of the screening, diagnosis, treatment and follow-up processes and invite them to partake. In Phase 3, the research team will collect data on the outcomes of the modified processes and the outcomes for the women who have and have not participated. The data shall be analysed quantitatively and thematically in Phase 4 with Aboriginal community representatives and reported back to community. Lastly, in Phase 5, we evaluate the co-design process and adapt our protocol for use in partnership with other communities. ETHICS AND DISSEMINATION: This study has ethics approval of the Aboriginal Health and Medical Research Council ref:1525/19. The findings will be published in the literature, presented at conferences and short summaries will be issued via social media.

What Is the Evidence Globally for Culturally Safe Strategies to Improve Breast Cancer Outcomes for Indigenous Women in High Income Countries? A Systematic Review.

The aim was to systematically assess the evidence on whether cultural safety affects breast cancer outcomes with regards to care for Indigenous women in high income countries. We conducted a systematic review in accordance with PRISMA guidelines of peer-reviewed articles in Medline, EMBASE, CINAHL, Scopus, Web of Science, Proquest Sociology and Informit Rural health database and Indigenous collection databases. Key inclusion criteria were: adult female patients with breast cancer; high income country setting; outcome measure, including screening, diagnosis, treatment and follow up care. A total of 15 were selected. We developed a Community Engagement assessment tool in consultation with aboriginal researchers, based on the National Health and Medical Research Councils' community engagement guidelines, against which studies were appraised. This novel element allowed us to evaluate the literature from a new and highly relevant perspective. Thematic analysis of all 15 studies was also undertaken. Despite limited literature there are evidence-based strategies that are likely to improve outcomes for Indigenous women with breast cancer in high income countries and indicate that culture makes a positive difference. It is also clear that strong Indigenous community leadership and governance at all stages of the research including design is an imperative for feasibility.

Cost-Effectiveness Analysis from a Randomized Controlled Trial of Tailored Exercise Prescription for Women with Breast Cancer with 8-Year Follow-Up.

Studies show conflicting results on whether exercise interventions to improve outcomes for women with breast cancer are cost-effective. We modelled the long-term cost-effectiveness of the Exercise for Health intervention compared with usual care. A lifetime Markov cohort model for women with early breast cancer was constructed taking a societal perspective. Data were obtained from trial, epidemiological, quality of life, and healthcare cost reports. Outcomes were calculated from 5000 Monte Carlo simulations, and one-way and probabilistic sensitivity analyses. Over the cohort's remaining life, the incremental cost for the exercise versus usual care groups were $7409 and quality-adjusted life years (QALYs) gained were 0.35 resulting in an incremental cost per QALY ratio of AU$21,247 (95% Uncertainty Interval (UI): Dominant, AU$31,398). The likelihood that the exercise intervention was cost-effective at acceptable levels was 93.0%. The incremental cost per life year gained was AU$8894 (95% UI Dominant, AU$11,769) with a 99.4% probability of being cost effective. Findings were most sensitive to the probability of recurrence in the exercise and usual care groups, followed by the costs of out-of-pocket expenses and the model starting age. This exercise intervention for women after early-stage breast cancer is cost-effective and would be a sound investment of healthcare resources.

Breast Cancer Incidence and Survival Among Young Females in Queensland, Australia.

Purpose: Breast cancer is the most common cancer diagnosed among adolescent and young adult (AYA) females worldwide, but epidemiological patterns unique to this group are often obscured when results are combined with older patients. This study investigates breast cancer incidence and survival among AYA females, including differences by broad stage at diagnosis. Methods: A retrospective, population-based cohort study was conducted using de-identified data for females in Queensland, Australia, aged 15-39 diagnosed with a first primary breast cancer between 1997 and 2014 with follow-up to December 31, 2016. Incidence rate trends were examined with Joinpoint analysis. Cause-specific survival was calculated for key characteristics, and 5-year adjusted hazard ratios (HRs) were estimated from a multivariable flexible parametric model. Results: The study cohort comprised 2337 patients, of whom two-thirds (n = 1565, 67%) were diagnosed with advanced disease (tumor diameter >20 mm, lymph node involvement or presence of distant metastases at diagnosis). Incidence rates of localized tumors decreased by 1.9% per year (95% confidence interval [CI] -3.5% to -0.4%) over the study period, whereas the trend for advanced breast cancers remained stable. Five-year cause-specific survival increased from 85% to 92% for 2011-2014 compared to 1997-2001 (adjusted HR = 0.43, 95% CI = 0.29-0.65). Patients who were Indigenous from disadvantaged areas or diagnosed with advanced stage experienced significantly worse survival. Conclusion: The high proportion of younger females diagnosed with advanced breast cancer should be the focus of future campaigns to improve awareness and earlier detection. While survival has increased over time, further work is required to ensure that this progress is experienced equitably by all patients.

Improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-α and progesterone receptor-b.

BACKGROUND: Recent pre-clinical studies indicate that activated progesterone receptor (PR) (particularly the PR-B isoform) binds to oestrogen receptor-α (ER) and reprogrammes transcription toward better breast cancer outcomes. We investigated whether ER and PR-B interactions were present in breast tumours and associated with clinical parameters including response to aromatase inhibitors. METHODS: We developed a proximity ligation assay to detect ER and PR-B (ER:PR-B) interactions in formalin-fixed paraffin-embedded tissues. The assay was validated in a cell line and patient-derived breast cancer explants and applied to a cohort of 229 patients with ER-positive and HER2-negative breast cancer with axillary nodal disease. RESULTS: Higher frequency of ER:PR-B interaction correlated with increasing patient age, lower tumour grade and mitotic index. A low frequency of ER:PR-B interaction was associated with higher risk of relapse. In multivariate analysis, ER:PR-B interaction frequency was an independent predictive factor for relapse, whereas PR expression was not. In subset analysis, low frequency of ER:PR-B interaction was predictive of relapse on adjuvant aromatase inhibitor (HR 4.831, p = 0.001), but not on tamoxifen (HR 1.043, p = 0.939). CONCLUSIONS: This study demonstrates that ER:PR-B interactions have utility in predicting patient response to adjuvant AI therapy.

Competing mortality risks among women aged 50-79 years when diagnosed with invasive breast cancer, Queensland, 1997-2012.

BACKGROUND: Understanding the burden of competing (non-breast cancer) mortality is important for the growing number of breast cancer survivors. We quantity these patterns, and the impact of two leading non-cancer causes of death, within ten years of breast cancer diagnosis. METHODS: Population based cancer registry study of 23,809 women aged 50-79 diagnosed with first primary breast cancer in Queensland, Australia, 1997 to 2012 with additional data linkage to identify individual non-cancer mortality causes. Flexible parametric competing-risks models were used to estimate the crude and adjusted probabilities of death. RESULTS: While overall mortality increased with age at diagnosis, this effect was strongest for non-cancer (such as cardiovascular and cerebrovascular disease) mortality. Women diagnosed with advanced breast cancer had a higher crude probability of breast cancer death (23.1% versus 4.5% for localised) but similar probability of competing mortality (11.6% versus 11.3%). Within each category of spread of disease, the probability of breast-cancer deaths remained relatively constant with age, while the probability of competing deaths increased. The 10-year probability of dying from breast cancer was 3.7%, 4.2% and 5.6% among women with localised disease aged 50 to 59, 60-69 and 70-79 respectively, but 3.1%, 7.8% and 22.9% for competing mortality. Increasing age, advanced disease and being unpartnered were independently associated with increased risk of breast cancer and competing deaths. CONCLUSIONS: Promotion of improved health behaviors after a cancer diagnosis and development of individualized strategies for clinical management should be prioritized as part of optimal care for breast cancer survivors.

Sentinel node biopsy for early breast cancer in Queensland, Australia, during 2008-2012.

BACKGROUND: Sentinel node biopsy (SNB) is now the standard of care for women with early-stage breast cancer. Despite lower morbidity than axillary lymph node dissection, widespread variation in SNB rates by non-clinical factors persists. We explored the factors associated with SNB usage and changes in those associations over time for recently diagnosed women. METHODS: We report here on a linked population-based cancer registry and hospital inpatient admission data set for 5577 women aged at least 20 years diagnosed with a first primary invasive early-stage node-negative breast cancer from July 2008 to 2012 in Queensland, Australia, who underwent breast cancer-related surgery within 2 years of diagnosis. Multivariate logistic regression was used to model predictors of SNB separately for 5172 women with ≤30 mm tumours and 405 with 31 to ≤50 mm tumours. RESULTS: Overall, 3972 (77%) women with ≤30 mm tumours and 221 (55%) of those with larger tumours underwent SNB. Usage increased over time for both cohorts but was consistently lower among those with larger tumours. A more recent diagnosis, having breast-conserving surgery, living in more accessible areas and attending a private or high-volume hospital independently increased the odds of SNB for both cohorts. There was no evidence that the geographical disparity had reduced over the study period for either cohort. CONCLUSION: Geographical disparities to accessing SNB persist. Efforts to promote multidisciplinary care and facilitate education in healthcare changes through innovative solutions using emerging technologies as well as targeted research to identify the barriers to equitable access remain critical.

Absent progesterone receptor expression in the lymph node metastases of ER-positive, HER2-negative breast cancer is associated with relapse on tamoxifen.

AIMS: Progesterone receptor (PR) expression is prognostic in early stage breast cancer. There are several reports of discordant expression between primary tumour and axillary lymph node (ALN) metastasis expression of oestrogen receptor (ER) and PR. We sought to determine whether expression of these biomarkers in the synchronous ALN metastases of ER positive (+), HER2 negative (-) breast cancer could provide more accurate prognostic information. METHODS: The retrospective cohort included 229 patients from a single institution with ER+, HER2- breast cancer who had synchronous ALN metastatic disease (2005-2014). PR expression was correlated with relapse-free survival, and subset analysis was performed for patients who received adjuvant tamoxifen or an aromatase inhibitor. RESULTS: One patient had an ER+ primary tumour, which was ER- in the ALN metastasis. 27 (11.3%) were PR- in the primary tumour and 56 (23.6%) in the ALN metastasis. The predominant change was from PR+ in the primary tumour to PR- in the lymph node. Absence of PR expression in the ALN was significantly associated with relapse; however, this was not the case in the primary tumour. In a subset analysis of patients taking adjuvant endocrine therapy, poorer prognosis was limited to those with PR- metastases on tamoxifen (HR=5.203, 95% CI 1.649 to 16.416, p=0.005). No significant prognostic effect of PR- metastases in patients taking aromatase inhibitors was seen (HR=1.519, 95% CI 0.675 to 3.418, p=0.312). CONCLUSIONS: Evaluation of PR expression in ALN metastasis may enable prediction of patients who are less likely to benefit from adjuvant tamoxifen. This study should be replicated in other cohorts.

Geographical disparity in breast reconstruction following mastectomy has reduced over time.

BACKGROUND: Breast reconstruction (BR) following mastectomy for breast cancer has been shown to improve quality of life and body image; however, there is significant geographic variation in BR rates. We explored factors associated with BR following mastectomy. METHODS: This is a population-based data linkage study consisting of cancer registry records linked to hospital inpatient episodes for 4104 women aged 20 years and over-diagnosed with a first primary invasive localized stage breast cancer between 1997 and 2012 in Queensland, Australia, who underwent a mastectomy. Multivariate logistic regression was used to model predictors of BR. RESULTS: Overall, 481 women (11.7%) underwent reconstruction. Proportions increased over time and were higher for younger women. Younger age, more recent diagnosis, living in high or very high accessibility areas or less disadvantaged areas, smaller tumours and attending a private or high-volume hospital independently increased the odds of reconstruction. The geographical disparity reduced significantly over time. CONCLUSION: Geographical barriers to accessing BR have reduced; however, continued monitoring and further research to inform strategies to further reduce subgroup disparities remain a priority.

The Impact of Rurality and Disadvantage on the Diagnostic Interval for Breast Cancer in a Large Population-Based Study of 3202 Women in Queensland, Australia.

Delays in diagnosing breast cancer (BC) can lead to poorer outcomes. We investigated factors related to the diagnostic interval in a population-based cohort of 3202 women diagnosed with BC in Queensland, Australia. Interviews ascertained method of detection and dates of medical/procedural appointments, and clinical information was obtained from medical records. Time intervals were calculated from self-recognition of symptoms (symptom-detected) or mammogram (screen-detected) to diagnosis (diagnostic interval (DI)). The cohort included 1560 women with symptom-detected and 1642 with screen-detected BC. Symptom-detected women had higher odds of DI of >60 days if they were Indigenous (OR = 3.12, 95% CI = 1.40, 6.98); lived in outer regional (OR = 1.50, 95% CI = 1.09, 2.06) or remote locations (OR = 2.46, 95% CI = 1.39, 4.38); or presented with a "non-lump" symptom (OR = 1.84, 95% CI = 1.43, 2.36). For screen-detected BC, women who were Indigenous (OR = 2.36, 95% CI = 1.03, 5.80); lived in remote locations (OR = 2.35, 95% CI = 1.24, 4.44); or disadvantaged areas (OR = 1.69, 95% CI = 1.17, 2.43) and attended a public screening facility (OR = 2.10, 95% CI = 1.40, 3.17) had higher odds of DI > 30 days. Our study indicates a disadvantage in terms of DI for rural, disadvantaged and Indigenous women. Difficulties in accessing primary care and diagnostic services are evident. There is a need to identify and implement an efficient and effective model of care to minimize avoidable longer diagnostic intervals.

Geographical Inequalities in Surgical Treatment for Localized Female Breast Cancer, Queensland, Australia 1997-2011: Improvements over Time but Inequalities Remain.

The uptake of breast conserving surgery (BCS) for early stage breast cancer varies by where women live. We investigate whether these geographical patterns have changed over time using population-based data linkage between cancer registry records and hospital inpatient episodes. The study cohort consisted of 11,631 women aged 20 years and over diagnosed with a single primary invasive localised breast cancer between 1997 and 2011 in Queensland, Australia who underwent either BCS (n = 9223, 79%) or mastectomy (n = 2408, 21%). After adjustment for socio-demographic and clinical factors, compared to women living in very high accessibility areas, women in high (Odds Ratio (OR) 0.58 (95% confidence intervals (CI) 0.49, 0.69)), low (OR 0.47 (0.41, 0.54)) and very low (OR 0.44 (0.34, 0.56)) accessibility areas had lower odds of having BCS, while  the odds for women from middle (OR 0.81 (0.69, 0.94)) and most disadvantaged (OR 0.87 (0.71, 0.98)) areas was significantly lower than women living in affluent areas. The association between accessibility and the type of surgery reduced over time (interaction p = 0.028) but not for area disadvantage (interaction p = 0.209). In making informed decisions about surgical treatment, it is crucial that any geographical-related barriers to implementing their preferred treatment are minimised.

The descriptive epidemiology of female breast cancer: an international comparison of screening, incidence, survival and mortality.

BACKGROUND: This paper presents the latest international descriptive epidemiological data for invasive breast cancer amongst women, including incidence, survival and mortality, as well as information on mammographic screening programmes. RESULTS: Almost 1.4 million women were diagnosed with breast cancer worldwide in 2008 and approximately 459,000 deaths were recorded. Incidence rates were much higher in more developed countries compared to less developed countries (71.7/100,000 and 29.3/100,000 respectively, adjusted to the World 2000 Standard Population) whereas the corresponding mortality rates were 17.1/100,000 and 11.8/100,000. Five-year relative survival estimates range from 12% in parts of Africa to almost 90% in the United States, Australia and Canada, with the differential linked to a combination of early detection, access to treatment services and cultural barriers. Observed improvements in breast cancer survival in more developed parts of the world over recent decades have been attributed to the introduction of population-based screening using mammography and the systemic use of adjuvant therapies. CONCLUSION: The future worldwide breast cancer burden will be strongly influenced by large predicted rises in incidence throughout parts of Asia due to an increasingly "westernised" lifestyle. Efforts are underway to reduce the global disparities in survival for women with breast cancer using cost-effective interventions.

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.

A population of HLA-DR+ immature cells accumulates in the blood dendritic cell compartment of patients with different types of cancer.

Dendritic cell (DC) defects are an important component of immunosuppression in cancer. Here, we assessed whether cancer could affect circulating DC populations and its correlation with tumor progression. The blood DC compartment was evaluated in 136 patients with breast cancer, prostate cancer, and malignant glioma. Phenotypic, quantitative, and functional analyses were performed at various stages of disease. Patients had significantly fewer circulating myeloid (CD11c+) and plasmacytoid (CD123+) DC, and a concurrent accumulation of CD11c(-)CD123(-) immature cells that expressed high levels of HLA-DR+ immature cells (DR(+)IC). Although DR(+)IC exhibited a limited expression of markers ascribed to mature hematopoietic lineages, expression of HLA-DR, CD40, and CD86 suggested a role as antigen-presenting cells. Nevertheless, DR(+)IC had reduced capacity to capture antigens and elicited poor proliferation and interferon-gamma secretion by T-lymphocytes. Importantly, increased numbers of DR(+)IC correlated with disease status. Patients with metastatic breast cancer showed a larger number of DR(+)IC in the circulation than patients with local/nodal disease. Similarly, in patients with fully resected glioma, the proportion of DR(+)IC in the blood increased when evaluation indicated tumor recurrence. Reduction of blood DC correlating with accumulation of a population of immature cells with poor immunologic function may be associated with increased immunodeficiency observed in cancer.

Atypical ductal hyperplasia of the breast in young women: two case reports.

Atypical ductal hyperplasia of the breast is a benign proliferative condition that is associated with an increased risk of development of breast cancer in either the ipsilateral or contralateral breast. Following diagnosis at biopsy, respective management options range from observation to chemoprophylaxis to prophylactic surgery. We present two cases in young women, facing prolonged follow-up, one managed with observation only, and the other managed with ipsilateral mastectomy and reconstruction.