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About 125,000 people are diagnosed with cancer in Australia each year. With population growth and aging this is set to rise to 150,000 new cases each year by 2020.1 in 2 Australian men and 1 in 3 Australian women will be diagnosed with cancer by the age of 85. Cancer is a leading cause of death in Australia. (Source: Cancer Council Australia)

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Western Australia
Latest Research Publications

National Organisations (32 links)

New South Wales (10 links)

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Latest Research Publications

Doherty DA, Newnham JP, Bower C, Hart R
Implications of polycystic ovary syndrome for pregnancy and for the health of offspring.
Obstet Gynecol. 2015; 125(6):1397-406 [PubMed] Related Publications
OBJECTIVE: To study the influence of polycystic ovary syndrome (PCOS) on obstetric and perinatal outcomes and on offspring in childhood.
METHODS: Using statewide data linkage systems within Western Australia, 2,566 hospitalized women with a PCOS diagnosis and at least one pregnancy at 20 weeks of gestation or greater, between 1997 and 2011, were compared with 25,660 randomly selected age-matched women not hospitalized with a PCOS diagnosis with regard to perinatal outcomes, congenital anomalies, and general health of offspring. Hospitalizations were categorized by International Classification of Diseases, 10th Revision diagnoses and rates by 10 years by Kaplan-Meier estimates. Polycystic ovary syndrome effects were summarized using adjusted odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) after controlling for maternal and perinatal characteristics, including maternal diabetes and obesity.
RESULTS: Of women with PCOS (n=1,789), 69.7% and 62.9% (n=16,139) of women without PCOS had one or more births. Hospitalizations up to 31 years were examined for 38,361 offspring. Offspring of women with PCOS were at higher risk of preterm birth (15.5% compared with 7.6% OR 1.74, 95% CI 1.53-1.98), perinatal mortality (2.3% compared with 0.7%, OR 1.49, 95% CI 1.02-2.18), more postnatal hospitalizations (14.1% compared with 7.9%, OR 1.21, 95% CI 1.05-1.40), more congenital anomalies (6.3% compared with 4.9%, OR 1.20, 95% CI 1.03-1.40), cardiovascular (1.5% compared with 1.0%, OR 1.37, 95% CI 1.01-1.87), and urogenital defects (2.0% compared with 1.4% OR 1.36, 95% CI 1.03-1.81). Maternal PCOS was associated with increased hospitalizations for their offspring, including metabolic disorder (7.9% compared with 5.3%, HR 1.43, 95% CI 1.26-1.65), disease of the nervous system (9.4% compared with 6.9%, HR 1.17, 95% CI 1.03-1.33), and asthma (6.9% compared with 4.9%, HR 1.32, 95% CI 1.13-1.54).
CONCLUSION: Controlling for increased perinatal risk, maternal PCOS was associated with a predisposition to adverse health outcomes for their offspring.

Fortunato L, Rushton L
Stomach cancer and occupational exposure to asbestos: a meta-analysis of occupational cohort studies.
Br J Cancer. 2015; 112(11):1805-15 [PubMed] Related Publications
BACKGROUND: A recent Monographs Working Group of the International Agency for Research on Cancer concluded that there is limited evidence for a causal association between exposure to asbestos and stomach cancer.
METHODS: We performed a meta-analysis to quantitatively evaluate this association. Random effects models were used to summarise the relative risks across studies. Sources of heterogeneity were explored through subgroup analyses and meta-regression.
RESULTS: We identified 40 mortality cohort studies from 37 separate papers, and cancer incidence data were extracted for 15 separate cohorts from 14 papers. The overall meta-SMR for stomach cancer for total cohort was 1.15 (95% confidence interval 1.03-1.27), with heterogeneous results across studies. Statistically significant excesses were observed in North America and Australia but not in Europe, and for generic asbestos workers and insulators. Meta-SMRs were larger for cohorts reporting a SMR for lung cancer above 2 and cohort sizes below 1000.
CONCLUSIONS: Our results support the conclusion by IARC that exposure to asbestos is associated with a moderate increased risk of stomach cancer.

Small AG, Thwe le M, Byrne JA, et al.
Neuroblastoma, body mass index, and survival: a retrospective analysis.
Medicine (Baltimore). 2015; 94(14):e713 [PubMed] Related Publications
Extremes of body mass index (BMI) at diagnosis of childhood cancers have been associated with poorer prognosis. The aims of this retrospective review were to examine the growth and BMI status of children diagnosed with neuroblastoma (NB) and determine if BMI status at diagnosis affected survival. Between 1985 and 2005, 154 children were diagnosed with NB at Sydney Children's Hospitals Network (Westmead), Australia, of which 129 had both length/height and weight recorded in the medical records at diagnosis. BMI was calculated and children were classified as underweight (BMI <15th percentile), normal weight, and overweight (BMI >85th percentile). Disease stage was classified according to the International NB Staging System. At diagnosis, 24.0% of the children were classified as underweight and 11.6% were overweight. Six months after diagnosis all children except those with stage 4s disease had a decrease in BMI z-score; difference in estimated marginal mean -0.73, P < .001. After 12 months an increase in BMI z-score was observed and by 2 years BMI z-score was significantly higher than BMI z-score at baseline; difference in estimated marginal mean 0.81, P = .007. At the last follow-up (median 5.6 years [range 3-7] after diagnosis) the proportion of children who were classified as underweight decreased to 8.7% and the proportion of children who were classified as overweight increased to 27.5%. The overall survival rate was 61.2%; however, BMI status did not predict survival. In multivariable Cox regression modeling, stage at diagnosis was the only predictor of survival; children diagnosed with stage 4 were less likely to survive (hazard ratio [HR] [95%CI]: 7.02 [1.7-29.0], P = .007). Almost a quarter of children with NB were underweight at diagnosis. However, we did not demonstrate a prognostic association between BMI status and survival. The high proportion of children who were classified as overweight at follow-up indicates a need for nutritional interventions to prevent potential late effects.

Ivey KL, Hodgson JM, Croft KD, et al.
Flavonoid intake and all-cause mortality.
Am J Clin Nutr. 2015; 101(5):1012-20 [PubMed] Related Publications
BACKGROUND: Flavonoids are bioactive compounds found in foods such as tea, chocolate, red wine, fruit, and vegetables. Higher intakes of specific flavonoids and flavonoid-rich foods have been linked to reduced mortality from specific vascular diseases and cancers. However, the importance of flavonoids in preventing all-cause mortality remains uncertain.
OBJECTIVE: The objective was to explore the association between flavonoid intake and risk of 5-y mortality from all causes by using 2 comprehensive food composition databases to assess flavonoid intake.
DESIGN: The study population included 1063 randomly selected women aged >75 y. All-cause, cancer, and cardiovascular mortalities were assessed over 5 y of follow-up through the Western Australia Data Linkage System. Two estimates of flavonoid intake (total flavonoidUSDA and total flavonoidPE) were determined by using food composition data from the USDA and the Phenol-Explorer (PE) databases, respectively.
RESULTS: During the 5-y follow-up period, 129 (12%) deaths were documented. Participants with high total flavonoid intake were at lower risk [multivariate-adjusted HR (95% CI)] of 5-y all-cause mortality than those with low total flavonoid consumption [total flavonoidUSDA: 0.37 (0.22, 0.58); total flavonoidPE: 0.36 (0.22, 0.60)]. Similar beneficial relations were observed for both cardiovascular disease mortality [total flavonoidUSDA: 0.34 (0.17, 0.69); flavonoidPE: 0.32 (0.16, 0.61)] and cancer mortality [total flavonoidUSDA: 0.25 (0.10, 0.62); flavonoidPE: 0.26 (0.11, 0.62)].
CONCLUSIONS: Using the most comprehensive flavonoid databases, we provide evidence that high consumption of flavonoids is associated with reduced risk of mortality in older women. The benefits of flavonoids may extend to the etiology of cancer and cardiovascular disease.

Jaimes N, Marghoob AA, Rabinovitz H, et al.
Clinical and dermoscopic characteristics of melanomas on nonfacial chronically sun-damaged skin.
J Am Acad Dermatol. 2015; 72(6):1027-35 [PubMed] Related Publications
BACKGROUND: Melanomas on chronically sun-damaged skin (CSDS) can be difficult to identify and often manifest morphologic features that overlap with benign lesions.
OBJECTIVE: We describe and analyze the clinical and dermoscopic characteristics of melanomas on nonfacial CSDS.
METHODS: Melanoma cases on nonfacial CSDS were retrospectively identified from the biopsy specimen logs of 6 melanoma clinics. Clinical and dermoscopic images were combined into 1 database. Demographics, clinical, dermoscopic, and histopathologic information were analyzed. Descriptive frequencies were calculated.
RESULTS: One hundred eighty-six cases met the inclusion criteria: 142 melanomas in situ (76%) and 39 invasive (21%; mean thickness, 0.49 mm). Lentigo maligna was the most common histopathologic subtype (n = 76; 40.9%). The most frequent dermoscopic structures were granularity (n = 126; 67.7%) and angulated lines (n = 82; 44%). Vascular structures were more frequent in invasive melanomas (56% vs 12% of in situ melanomas). Most manifested 1 of 3 dermoscopic patterns: patchy peripheral pigmented islands, angulated lines, and tan structureless with granularity pattern.
LIMITATIONS: This was a retrospective study, and evaluators were not blinded to the diagnosis. In addition, interobserver concordance and sensitivity and specificity for dermoscopic structures were not evaluated.
CONCLUSION: Outlier lesions manifesting dermoscopic structures, such as granularity, angulated lines, or vessels and any of the 3 described dermoscopic patterns should raise suspicion for melanoma.

Sneddon S, Leon JS, Dick IM, et al.
Absence of germline mutations in BAP1 in sporadic cases of malignant mesothelioma.
Gene. 2015; 563(1):103-5 [PubMed] Related Publications
Malignant mesothelioma (MM) is a uniformly fatal tumour caused predominantly by exposure to asbestos. It is not known why some exposed individuals get mesothelioma and others do not. There is some epidemiological evidence of host susceptibility. BAP1 gene somatic mutations and allelic loss are common in mesothelioma and recently a BAP1 cancer syndrome was described in which affected individuals and families had an increased risk of cancer of multiple types, including MM. To determine if BAP1 mutations could underlie any of the sporadic mesothelioma cases in our cohort of patients, we performed targeted deep sequencing of the BAP1 exome on the IonTorrent Proton sequencer in 115 unrelated MM cases. No exonic germline BAP1 mutations of known functional significance were observed, further supporting the notion that sporadic germline BAP1 mutations are not relevant to the genetic susceptibility of MM.

Suen MK, Zahid A, Young JM, et al.
How to decide to undertake a randomized, controlled trial of stent or surgery in colorectal obstruction.
Surgery. 2015; 157(6):1137-41 [PubMed] Related Publications
BACKGROUND: Colorectal stents have been available as a management option in obstruction for 23 years, yet there is little randomized evidence of their effectiveness. This study investigated current surgeon-related barriers to conducting a randomized, controlled trial (RCT) of colorectal stent insertion for obstruction in patients with colorectal cancer.
METHODS: A binational survey of current members of the Colorectal Surgical Society of Australia and New Zealand was conducted by a mailed questionnaire assessing perceived barriers to adoption of colonic stents and willingness to participate in future multicentre randomized controlled trials, and surgeons' treatment preferences in 16 hypothetical clinical scenarios.
RESULTS: Of 148 eligible surgeons, 96 (65%) responded. Colonic stenting was available to 98% of respondents. In the clinical setting of colorectal obstruction, only 29% (95% CI, 20-39%) of surgeons expressed a willingness to participate in a RCT involving colonic stents in the curative setting. More than 70% of surgeons preferred the use of stents in unfit patients for palliation, and preferred surgery in fit patients with curable disease. In the curative setting, most respondents considered colonic stents not cost effective (90%; 95% CI, 82-94%) and believed that their patients would not prefer stents over surgery (80%; 95% CI, 71-87%).
CONCLUSION: This study highlights the limitation to conducting a future randomized controlled trial to assess the efficacy of colonic stenting, especially in the curative setting, based on surgeon preference, despite the lack of level I evidence.

Chiang PP, Glance D, Walker J, et al.
Implementing a QCancer risk tool into general practice consultations: an exploratory study using simulated consultations with Australian general practitioners.
Br J Cancer. 2015; 112 Suppl 1:S77-83 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Reducing diagnostic delays in primary care by improving the assessment of symptoms associated with cancer could have significant impacts on cancer outcomes. Symptom risk assessment tools could improve the diagnostic assessment of patients with symptoms suggestive of cancer in primary care. We aimed to explore the use of a cancer risk tool, which implements the QCancer model, in consultations and its potential impact on clinical decision making.
METHODS: We implemented an exploratory 'action design' method with 15 general practitioners (GPs) from Victoria, Australia. General practitioners applied the risk tool in simulated consultations, conducted semi-structured interviews based on the normalisation process theory and explored issues relating to implementation of the tool.
RESULTS: The risk tool was perceived as being potentially useful for patients with complex histories. More experienced GPs were distrustful of the risk output, especially when it conflicted with their clinical judgement. Variable interpretation of symptoms meant that there was significant variation in risk assessment. When a risk output was high, GPs were confronted with numerical risk outputs creating challenges in consultation.
CONCLUSIONS: Significant barriers to implementing electronic cancer risk assessment tools in consultation could limit their uptake. These relate not only to the design and integration of the tool but also to variation in interpretation of clinical histories, and therefore variable risk outputs and strong beliefs in personal clinical intuition.

Allen K, Farah CS
Screening and referral of oral mucosal pathology: a check-up of Australian dentists.
Aust Dent J. 2015; 60(1):52-8 [PubMed] Related Publications
BACKGROUND: Oral squamous cell carcinomas and potentially malignant oral disorders can be detected early by visually inspecting the oral soft tissues. This study aimed to determine Australian dentists' opinions and practices regarding oral mucosal screening, referral and oral cancer prevention.
METHODS: Nine hundred and ninety-nine randomly selected general dentists were mailed a questionnaire. The questionnaire queried practitioners' opinions and perceptions of oral mucosal screening, their referral practices and their beliefs regarding detection and prevention of oral cancer.
RESULTS: A total of n=640 individuals responded, yielding a response rate of 70.2%. Most Australian dentists reported to routinely perform oral mucosal screening. Lack of training, confidence, time and financial incentives were seen as barriers to performing mucosal screening to at least some degree by participants in this study. Most dentists manage referrals for oral mucosal pathology appropriately; however, only about half believe in following up with referred patients. Only half of dentists surveyed believed that they could influence a patient to quit smoking.
CONCLUSIONS: Australian dentists place importance on oral mucosal screening. Some changes to dental education and training could be made to further improve confidence and ability of dentists in detecting and referring oral mucosal pathology.

Gibberd A, Supramaniam R, Dillon A, et al.
Are Aboriginal people more likely to be diagnosed with more advanced cancer?
Med J Aust. 2015; 202(4):195-9 [PubMed] Related Publications
OBJECTIVE: To determine whether Aboriginal people in New South Wales were diagnosed with more advanced cancer than non-Aboriginal people.
DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study of cancer cases, excluding lymphohaematopoietic cancers and cancers of unknown primary site, diagnosed in NSW in 2001-2007.
MAIN OUTCOME MEASURE: Spread of disease at time of cancer diagnosis.
RESULTS: Overall, 40.3% of 2039 cancers in Aboriginal people and 46.6% of 191 954 cancers in non-Aboriginal people were localised at diagnosis. After adjusting for age, sex, year of diagnosis, area of residence and socioeconomic status, Aboriginal people had significantly higher risks of regional or distant spread for head and neck cancer, relative to localised spread, than non-Aboriginal people (regional: adjusted relative risk ratio [RRR], 1.89; 95% CI, 1.21-2.98; distant: adjusted RRR, 3.40; 95% CI, 1.85-6.05; P < 0.001). For breast, cervical and prostate cancers and melanoma, the risks of regional or distant spread were higher for Aboriginal people, but these differences were not statistically significant. For lung, colorectal, upper gastrointestinal tract, other gynaecological, and eye, brain and central nervous system cancers, the risks of regional, distant and unknown spread of cancer were similar for Aboriginal and non-Aboriginal people.
CONCLUSION: Aboriginal people were more likely than non-Aboriginal people to be diagnosed with more advanced cancer for only a few cancer types, most notably head and neck cancers. Differences in spread of disease at diagnosis are unlikely to explain much of the survival differences observed across a wide range of cancers between Aboriginal and non-Aboriginal people in NSW.

Sammour T, Jones IT, Gibbs P, et al.
Comparing oncological outcomes of laparoscopic versus open surgery for colon cancer: Analysis of a large prospective clinical database.
J Surg Oncol. 2015; 111(7):891-8 [PubMed] Related Publications
BACKGROUND: Oncological outcomes of laparoscopic colon cancer surgery have been shown to be equivalent to those of open surgery, but only in the setting of randomized controlled trials on highly selected patients. The aim of this study is to investigate whether this finding is generalizable to real world practice.
METHODS: Analysis of prospectively collected data from the BioGrid Australia database was undertaken. Overall and cancer specific survival rates were compared with cox regression analysis controlling for the confounders of age, sex, BMI, ASA score, hospital site, year surgery performed, procedure, tumor stage, and adjuvant chemotherapy.
RESULTS: Between 2003 and 2009, 1,106 patients underwent elective colon cancer resection. There were differences between the laparoscopic and open cohorts in BMI, procedure, post-operative complication rate, and tumor stage. When baseline confounders were accounted for using cox regression analysis, there was no difference in 5 year overall survival (χ(2) test 1.302, P = 0.254), or cancer specific survival (χ(2) test 0.028, P = 0.866).
CONCLUSION: This large prospective clinical study validates previous trial results, and confirms that there is no difference in oncological outcome between laparoscopic and open surgery for colon cancer.

Saad F, Fizazi K, Jinga V, et al.
Orteronel plus prednisone in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (ELM-PC 4): a double-blind, multicentre, phase 3, randomised, placebo-controlled trial.
Lancet Oncol. 2015; 16(3):338-48 [PubMed] Related Publications
BACKGROUND: Orteronel is an investigational, partially selective inhibitor of CYP 17,20-lyase in the androgen signalling pathway, a validated therapeutic target for metastatic castration-resistant prostate cancer. We assessed orteronel in chemotherapy-naive patients with metastatic castration-resistant prostate cancer.
METHODS: In this phase 3, double-blind, placebo-controlled trial, we recruited patients with progressive metastatic castration-resistant prostate cancer and no previous chemotherapy from 324 study centres (ie, hospitals or large urologic or group outpatient offices) in 43 countries. Eligible patients were randomly assigned in a 1:1 ratio to receive either 400 mg orteronel plus 5 mg prednisone twice daily or placebo plus 5 mg prednisone twice daily. Randomisation was done centrally with an interactive voice response system and patients were stratified by region (Europe, North America, and not Europe or North America) and the presence or absence of radiographic disease progression at baseline. The two primary endpoints were radiographic progression-free survival and overall survival, determined in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01193244.
FINDINGS: From Oct 31, 2010, to June 29, 2012, 2353 patients were assessed for eligibility. Of those, 1560 were randomly assigned to receive either orteronel plus prednisone (n=781) or placebo plus prednisone (n=779). The clinical cutoff date for the final analysis was Jan 15, 2014 (with 611 deaths). Median follow-up for radiographic progression-free survival was 8·4 months (IQR 3·7-16·6). Median radiographic progression-free survival was 13·8 months (95% CI 13·1-14·9) with orteronel plus prednisone and 8·7 months (8·3-10·9) with placebo plus prednisone (hazard ratio [HR] 0·71, 95% CI 0·63-0·80; p<0·0001). After a median follow-up of 20·7 months (IQR 14·2-25·4), median overall survival was 31·4 months (95% CI 28·6-not estimable) with orteronel plus prednisone and 29·5 months (27·0-not estimable) with placebo plus prednisone (HR 0·92, 95% CI 0·79-1·08; p=0·31). The most common grade 3 or worse adverse events were increased lipase (137 [17%] of 784 patients in the orteronel plus prednisone group vs 14 [2%] of 770 patients in the placebo plus prednisone group), increased amylase (77 [10%] vs nine [1%]), fatigue (50 [6%] vs 14 [2%]), and pulmonary embolism (40 [5%] vs 27 [4%]). Serious adverse events were reported in 358 [46%] patients receiving orteronel plus prednisone and in 292 [38%] patients receiving placebo plus prednisone.
INTERPRETATION: In chemotherapy-naive patients with metastatic castration-resistant prostate cancer, radiographic progression-free survival was prolonged with orteronel plus prednisone versus placebo plus prednisone. However, no improvement was noted in the other primary endpoint, overall survival. Orteronel plus prednisone was associated with increased toxic effects compared with placebo plus prednisone. On the basis of these and other data, orteronel is not undergoing further development in metastatic castration-resistant prostate cancer.
FUNDING: Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Slavova-Azmanova NS, Johnson CE, Platell C, et al.
Peer review of cancer multidisciplinary teams: is it acceptable in Australia?
Med J Aust. 2015; 202(3):144-7 [PubMed] Related Publications
OBJECTIVE: To develop a peer-review model for assessment and quality improvement of cancer multidisciplinary teams (MDTs) and qualitatively assess its feasibility and acceptability in Australia.
DESIGN, SETTING AND PARTICIPANTS: A peer-review methodology was developed, based on the United Kingdom's National Health Service peer-review model and a comprehensive literature review. This was pilot tested in three mature MDTs in different settings. Semi-structured interviews were conducted between December 2012 and July 2013 with all five peer reviewers and 17 MDT members. Thematic analysis was undertaken using a framework approach.
RESULTS: Peer reviewers and MDT members found the process reasonable, constructive and useful; however, those involved in the preparation for the review found it time-consuming. Most MDT members considered the final report accurate and reflective of their service. Recommendations in the report were met with mixed reactions: several MDT members perceived some recommendations to be particularly relevant, while others viewed the same recommendations as impractical or of limited value. Many participants were unsure if recommendations would be fully implemented. The majority saw value in the process and expressed support for its implementation locally and nationally; however, feedback suggests the most appropriate format is yet to be established.
CONCLUSIONS: Peer review of cancer MDTs is feasible and acceptable. We describe valuable lessons learnt and recognise that further development of the proposed peer-review model and national benchmarking of MDTs against established outcome measures is required if this process is to be widely implemented.

Philip J, Hudson P, Bostanci A, et al.
Metastatic non-small cell lung cancer: a benchmark for quality end-of-life cancer care?
Med J Aust. 2015; 202(3):139-43 [PubMed] Related Publications
OBJECTIVES: To investigate the quality of end-of-life care for patients with metastatic non-small cell lung cancer (NSCLC).
DESIGN AND PARTICIPANTS: Retrospective cohort study of patients from first hospitalisation for metastatic disease until death, using hospital, emergency department and death registration data from Victoria, Australia, between 1 July 2003 and 30 June 2010.
MAIN OUTCOME MEASURES: Emergency department and hospital use; aggressiveness of care including intensive care and chemotherapy in last 30 days; palliative and supportive care provision; and place of death.
RESULTS: Metastatic NSCLC patients underwent limited aggressive treatment such as intensive care (5%) and chemotherapy (< 1%) at the end of life; however, high numbers died in acute hospitals (42%) and 61% had a length of stay of greater than 14 days in the last month of life. Although 62% were referred to palliative care services, this occurred late in the illness. In a logistic regression model adjusted for year of metastasis, age, sex, metastatic site and survival, the odds ratio (OR) of dying in an acute hospital bed compared with death at home or in a hospice unit decreased with receipt of palliative care (OR, 0.25; 95% CI, 0.21-0.30) and multimodality supportive care (OR, 0.65; 95% CI, 0.56-0.75).
CONCLUSION: Because early palliative care for patients with metastatic NSCLC is recommended, we propose that this group be considered a benchmark of quality end-of-life care. Future work is required to determine appropriate quality-of-care targets in this and other cancer patient cohorts, with particular focus on the timeliness of palliative care engagement.

Jones SB, Whitford HS, Bond MJ
Burden on informal caregivers of elderly cancer survivors: risk versus resilience.
J Psychosoc Oncol. 2015; 33(2):178-98 [PubMed] Related Publications
This study assessed psychological morbidity and resilience, including the subjective burden of 76 caregivers of elderly cancer survivors utilizing a cross-sectional questionnaire. Participants were mainly elderly female spouses, sole-caregiving > 35 hours per week; 19.1% and 23.6% reported moderate or greater anxiety and depression, respectively. A significant regression model found depression, emotion-focused coping, and greater years since diagnosis as significant predictors of subjective caregiver burden. Thus, caregiving appears a dominant role for this group and the Brief Assessment Scale for Caregivers of the Medically Ill (BASC) appears to be an efficient screening tool for psychological morbidity in this under-supported group.

Sala MA, Dhillon R, Brookes D, et al.
Indications for diagnostic open biopsy of mammographic screen-detected lesions preoperatively diagnosed as fibroadenomas by needle biopsy and their outcomes.
Clin Radiol. 2015; 70(5):507-14 [PubMed] Related Publications
AIM: To identify the clinical, radiological, and histopathological factors that resulted in a diagnostic open biopsy of mammographic screen-detected lesions diagnosed preoperatively as fibroadenomas by needle biopsy.
MATERIALS AND METHODS: BreastScreen WA data over 10 year period from 1 January 1999 to 31 December 2008 was reviewed.
RESULTS: Among the 760,027 women screened in Western Australia between 1999 and 2008, 31 had a fine-needle aspiration (FNA) or a core biopsy (CB) diagnosing a fibroadenoma and subsequently underwent a diagnostic open biopsy (DOB). Three were preoperatively diagnosed as fibroadenoma by initial FNA but subsequent CB showed that these were not fibroadenomas and, therefore, were excluded from the present series. Of the 28 cases, DOB identified 21 fibroadenomas, two cellular fibroadenomas, two benign phyllodes tumours, one malignant phyllodes tumour, one fibroadenoma containing ductal carcinoma in situ (DCIS), and one case of a 40mm adenosis tumour with a small 5mm fibroadenoma. The lesions ranged from 5-100mm in size with an average size of 28mm. DOB and CB results were concordant in 25 (89%) of the cases. The primary clinical indications for undergoing DOB included indeterminate histopathological findings of cellular fibroadenomas versus phyllodes tumour (n = 10), enlarging size (n = 4), large size (n = 5), fibroadenomas with atypia (n = 1), discordant radiological and pathological findings (n = 3), patient preference (n = 1), association with a second screen-detected lesion requiring excision (n = 2), and an unknown indication (n = 1).
CONCLUSION: CB diagnosis of fibroadenomas is a safe diagnosis unless it has atypical clinical, radiological, or pathological features.

Joham AE, Teede HJ, Ranasinha S, et al.
Prevalence of infertility and use of fertility treatment in women with polycystic ovary syndrome: data from a large community-based cohort study.
J Womens Health (Larchmt). 2015; 24(4):299-307 [PubMed] Related Publications
BACKGROUND: Polycystic ovary syndrome (PCOS) affects 6%-21% of women. PCOS is the primary cause of anovulatory infertility, with major health and economic costs, yet we are unaware of any community-based, natural history studies on fertility and fertility treatments published to date. We aim to compare infertility, fertility treatment use, and relationship to body mass index (BMI) in women reporting PCOS to women not reporting PCOS in a community-based population.
METHODS: This is a cross-sectional analysis of a longitudinal cohort study, the Australian Longitudinal Study on Women's Health (ALSWH). For the ALSWH, women from the general community were randomly selected from the national public insurance database. Mailed survey data were collected at multiple time points. At survey 4, there were 9145 respondents aged 28-33 years. Of 8612 women with known PCOS status, 478 women reported having PCOS. Information regarding fertility status was available for 4856 women. This was the subgroup used in this analysis. The main outcomes measures are self-reported PCOS status, BMI, infertility, and use of fertility therapies including ovulation induction and in vitro fertilization (IVF). Logistic regression was used to examine factors associated with infertility and use of fertility treatment.
RESULTS: Self-reported PCOS prevalence was 5.8% (95% confidence interval [CI]: 5.3%-6.4%). Infertility was noted by 72% of 309 women reporting PCOS, compared with 16% of 4547 women not reporting PCOS (p<0.001). Infertility was 15-fold higher in women reporting PCOS (adjusted odds ratio 14.9, 95% CI 10.9-20.3), independent of BMI. Of women reporting infertility, there was greater use of fertility hormone treatment, (62%, n=116 vs. 33%, n=162, p<0.001) in women reporting PCOS; however, IVF use was similar.
CONCLUSIONS: In this community-based cohort of women, infertility and use of fertility hormone treatment was significantly higher in women reporting PCOS. Considering the prevalence of PCOS and the health and economic burden of infertility, strategies to optimize fertility are important.

Kunkler IH, Williams LJ, Jack WJ, et al.
Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial.
Lancet Oncol. 2015; 16(3):266-73 [PubMed] Related Publications
BACKGROUND: For most older women with early breast cancer, standard treatment after breast-conserving surgery is adjuvant whole-breast radiotherapy and adjuvant endocrine treatment. We aimed to assess the effect omission of whole-breast radiotherapy would have on local control in older women at low risk of local recurrence at 5 years.
METHODS: Between April 16, 2003, and Dec 22, 2009, 1326 women aged 65 years or older with early breast cancer judged low-risk (ie, hormone receptor-positive, axillary node-negative, T1-T2 up to 3 cm at the longest dimension, and clear margins; grade 3 tumour histology or lymphovascular invasion, but not both, were permitted), who had had breast-conserving surgery and were receiving adjuvant endocrine treatment, were recruited into a phase 3 randomised controlled trial at 76 centres in four countries. Eligible patients were randomly assigned to either whole-breast radiotherapy (40-50 Gy in 15-25 fractions) or no radiotherapy by computer-generated permuted block randomisation, stratified by centre, with a block size of four. The primary endpoint was ipsilateral breast tumour recurrence. Follow-up continues and will end at the 10-year anniversary of the last randomised patient. Analyses were done by intention to treat. The trial is registered on ISRCTN.com, number ISRCTN95889329.
FINDINGS: 658 women who had undergone breast-conserving surgery and who were receiving adjuvant endocrine treatment were randomly assigned to receive whole-breast irradiation and 668 were allocated to no further treatment. After median follow-up of 5 years (IQR 3·84-6·05), ipsilateral breast tumour recurrence was 1·3% (95% CI 0·2-2·3; n=5) in women assigned to whole-breast radiotherapy and 4·1% (2·4-5·7; n=26) in those assigned no radiotherapy (p=0·0002). Compared with women allocated to whole-breast radiotherapy, the univariate hazard ratio for ipsilateral breast tumour recurrence in women assigned to no radiotherapy was 5·19 (95% CI 1·99-13·52; p=0·0007). No differences in regional recurrence, distant metastases, contralateral breast cancers, or new breast cancers were noted between groups. 5-year overall survival was 93·9% (95% CI 91·8-96·0) in both groups (p=0·34). 89 women died; eight of 49 patients allocated to no radiotherapy and four of 40 assigned to radiotherapy died from breast cancer.
INTERPRETATION: Postoperative whole-breast radiotherapy after breast-conserving surgery and adjuvant endocrine treatment resulted in a significant but modest reduction in local recurrence for women aged 65 years or older with early breast cancer 5 years after randomisation. However, the 5-year rate of ipsilateral breast tumour recurrence is probably low enough for omission of radiotherapy to be considered for some patients.
FUNDING: Chief Scientist Office (Scottish Government), Breast Cancer Institute (Western General Hospital, Edinburgh).

Thanh Pham T, Cross S, Gebski V, Veness MJ
Squamous cell carcinoma of the lip in Australian patients: definitive radiotherapy is an efficacious option to surgery in select patients.
Dermatol Surg. 2015; 41(2):219-25 [PubMed] Related Publications
BACKGROUND: In Australia, squamous cell carcinoma (SCC) of the lip is a consequence of chronic sun exposure and treated as a nonmelanoma skin cancer. Patients may be recommended radiotherapy (RT) as a treatment modality.
OBJECTIVE: To analyze the outcome of patients with early-stage SCC of the lip treated with definitive RT at Westmead Hospital, Sydney, Australia, between 1980 and 2012.
METHODS AND MATERIALS: Ninety-three patients with early-stage SCC of the lip underwent RT. All patients were clinically node negative based on examination and/or relevant investigations. Retrospective chart review was performed. Patients treated since 2000 had data collected and entered prospectively.
RESULTS: The most frequently involved site was the lower lip (93%). Fifty-six patients (60%) had T1N0 and 37 patients (40%) had T2N0 disease. Most patients were treated with superficial or orthovoltage RT, with the median RT dose delivered 55 Gy (range, 40 to 70 Gy). Local recurrence occurred in 5 patients (5%), whereas regional metastases developed in 5 patients (5%). One patient developed concurrent local and regional relapse. No patient developed distant metastases. The 5-year recurrence-free survival was 90%.
CONCLUSION: The findings confirm the efficacy of RT as an efficacious treatment option in early-stage lip SCC.

Wong E, Ling V, Westerman D, et al.
How unique is pure erythroid leukaemia? A retrospective analysis of seven cases and review of the literature.
J Clin Pathol. 2015; 68(4):301-5 [PubMed] Related Publications
AIMS: Pure erythroid leukaemia (PEL) is a rare subtype of acute myeloid leukaemia (AML) and its clinicopathological features are not well-defined. The aim of this study was to describe the immunophenotypic, cytogenetic and clinical features of PEL and to compare these with cases of AML with ≥ 50% erythroblasts.
METHODS: Cases of PEL according to WHO morphological criteria diagnosed at three institutions from 1997 to 2013 were included. A comparison cohort comprised of AML with ≥ 50% erythroblasts. The clinical, histopathology, immunophenotypic and cytogenetic features of cases were analysed. We also reviewed the existing literature on PEL, and combined our cohort with previously reported cases of PEL in a pooled analysis.
RESULTS: There were seven cases of PEL diagnosed at our institutions. There was a high incidence of either prior chemoradiotherapy exposure or evolution from pre-existing myelodysplastic syndrome (MDS) (71%). The leukaemic blasts frequently expressed glycophorin C (100%), CD117 (83%) and were myeloperoxidase negative (83%). Complex karyotypes were present in 83% of cases. Median overall survival was 2.9 months. Compared with AML with ≥ 50% erythroblasts, cases of PEL demonstrated a higher incidence of adverse-risk cytogenetics (p=0.01) and prior exposure to chemoradiotherapy (p=0.01).
CONCLUSIONS: PEL appears to be a unique entity that is often secondary or therapy related, commonly features a complex karyotype and has a poor prognosis. It is morphologically and immunophenotypically distinct from other cases of AML with erythroid hyperplasia.

Weerakoon M, Papa N, Lawrentschuk N, et al.
The current use of active surveillance in an Australian cohort of men: a pattern of care analysis from the Victorian Prostate Cancer Registry.
BJU Int. 2015; 115 Suppl 5:50-6 [PubMed] Related Publications
OBJECTIVES: To ascertain the treatment trends and patterns of care, for men with prostate cancer on active surveillance (AS) in Victoria, Australia.
PATIENTS AND METHODS: De-identified data was obtained for 6424 men from the Victorian Prostate Cancer Registry. Men included in this study were diagnosed with prostate cancer from 2008 to August 2012 with ≥ 12-months of follow-up. Patients were stratified using the National Comprehensive Cancer Network (NCCN) risk grouping system and those who were not actively treated were identified. Data was acquired to describe the trends and uptake of AS according to public vs private hospital sector, and regional vs metropolitan regions.
RESULTS: In all, 1603/6424 (24.9%) men received no treatment with curative intent at 12-months follow-up. This cohort included patients in whom the chosen management plan was recorded as AS (980/1603, 61.1%), watchful waiting (341/1603, 21.3%), or no management plan (282/1603, 17.6%). From this, 980/6424(15.3%) of the patients were recorded as being on AS across all NCCN categories at 12 months after diagnosis. This included 653/1816 (35.9%) of very low- and low-risk men, and 251/2820 (8.9%) of intermediate-risk men. Of our patients on AS, 169/980 (17.2%) progressed onto active treatment after 12 months. This active treatment included radical prostatectomy in 116 (68.6%), 32 (18.9%) undergoing external beam radiation therapy, 12 (7.1%) undergoingt brachytherapy and nine (5.3%) undergoing androgen-deprivation therapy. Overall, 629/979 (64.2%) of the AS patients were notified from a private hospital, with 350/979 (35.7%) of the patients notified from a public hospital (one patient unclassified). Of these, 202/652 (30.9%) of the AS patients with very low-/low-risk disease were managed in the public sector, vs 450/652 (69%) of very low-/low-risk AS patients being managed in the private sector. In our cohort, patients with very low- and low-risk disease, managed in a private hospital, were more likely to be on AS (P = 0.005). AS patients in the private sector were also a median of 2.8 years younger (median 65.6 vs 68.4 years, P < 0.001); had a lower median PSA level (5.3 vs 6.7 ng/mL, P < 0.001); and had lower biopsy Gleason score and clinical staging. There was no significant difference in the uptake of AS demographically, in our cohort of men between metropolitan and regional areas.
CONCLUSION: In this contemporary registry-based population, AS is being used in a significant proportion of patients. The proportion of men progressing to intervention is lower than that reported in the current literature. Patients are more likely to be on AS if they are managed in a private hospital, with no differences in the uptake of AS, from metropolitan to regional areas.

Dobbins TA, Creighton N, Currow DC, Young JM
Look back for the Charlson Index did not improve risk adjustment of cancer surgical outcomes.
J Clin Epidemiol. 2015; 68(4):379-86 [PubMed] Related Publications
OBJECTIVES: The Charlson score is a commonly used measure of comorbidity; however, there is little empirical research into the optimal implementation when studying cancer surgery outcomes using administrative data. We compared four alternative Charlson score implementations, including and excluding metastatic cancer and varying the look-back periods.
STUDY DESIGN AND SETTING: Nine years of linked administrative data were used to identify patients undergoing surgery for cancer of the colon, rectum, or lung in New South Wales, Australia. Four binary outcomes of 30- and 365-day mortality, length of stay greater than 21 days, and emergency readmission within 28 days were compared between groups of similar hospitals. Hospital risk adjustment models were compared for alternative Charlson score implementations.
RESULTS: Excluding metastatic cancer from the Charlson score improved model performance for short-term outcomes, but there was no implementation that was consistently optimal. Incorporating a look-back period reduced the number of patients for analysis but did not improve hospital risk adjustment.
CONCLUSION: Charlson scores for hospital risk adjustment of short-term outcomes of cancer surgery should be calculated excluding metastatic cancer as a separate comorbidity. We found no clear best performing implementation and found no benefit in incorporating any look-back period.

Olsen CM, Neale RE, Green AC, et al.
Independent validation of six melanoma risk prediction models.
J Invest Dermatol. 2015; 135(5):1377-84 [PubMed] Related Publications
Identifying people at high risk of melanoma is important for targeted prevention activities and surveillance. Several tools have been developed to classify melanoma risk, but few have been independently validated. We assessed the discriminatory performance of six melanoma prediction tools by applying them to individuals from two independent data sets, one comprising 762 melanoma cases and the second a population-based sample of 42,116 people without melanoma. We compared the model predictions with actual melanoma status to measure sensitivity and specificity. The performance of the models was variable with sensitivity ranging from 97.7 to 10.5% and specificity from 99.6 to 1.3%. The ability of all the models to discriminate between cases and controls, however, was generally high. The model developed by MacKie et al. (1989) had higher sensitivity and specificity for men (0.89 and 0.88) than women (0.79 and 0.72). The tool developed by Cho et al. (2005) was highly specific (men, 0.92; women, 0.99) but considerably less sensitive (men, 0.64; women, 0.37). Other models were either highly specific but lacked sensitivity or had low to very low specificity and higher sensitivity. Poor performance was partly attributable to the use of non-standardized assessment items and various differing interpretations of what constitutes "high risk".

Thomas R, Glasziou P, Rychetnik L, et al.
Deliberative democracy and cancer screening consent: a randomised control trial of the effect of a community jury on men's knowledge about and intentions to participate in PSA screening.
BMJ Open. 2014; 4(12):e005691 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: Prostate-specific antigen (PSA) screening is controversial. A community jury allows presentation of complex information and may clarify how participants view screening after being well-informed. We examined whether participating in a community jury had an effect on men's knowledge about and their intention to participate in PSA screening.
DESIGN: Random allocation to either a 2-day community jury or a control group, with preassessment, postassessment and 3-month follow-up assessment.
SETTING: Participants from the Gold Coast (Australia) recruited via radio, newspaper and community meetings.
PARTICIPANTS: Twenty-six men aged 50-70 years with no previous diagnosis of prostate cancer.
INTERVENTION: The control group (n=14) received factsheets on PSA screening. Community jury participants (n=12) received the same factsheets and further information about screening for prostate cancer. In addition, three experts presented information on PSA screening: a neutral scientific advisor provided background information, one expert emphasised the potential benefits of screening and another expert emphasised the potential harms. Participants discussed information, asked questions to the experts and deliberated on personal and policy decisions.
MAIN OUTCOME AND MEASURES: Our primary outcome was change in individual intention to have a PSA screening test. We also assessed knowledge about screening for prostate cancer.
RESULTS: Analyses were conducted using intention-to-treat. Immediately after the jury, the community jury group had less intention-to-screen for prostate cancer than men in the control group (effect size=-0.6 SD, p=0.05). This was sustained at 3-month follow-up. Community jury men also correctly identified PSA test accuracy and considered themselves more informed (effect size=1.2 SD, p<0.001).
CONCLUSIONS: Evidence-informed deliberation of the harms and benefits of PSA screening effects men's individual choice to be screened for prostate cancer. Community juries may be a valid method for eliciting target group input to policy decisions.
TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry (ACTRN12612001079831).

Hart R, Doherty DA
The potential implications of a PCOS diagnosis on a woman's long-term health using data linkage.
J Clin Endocrinol Metab. 2015; 100(3):911-9 [PubMed] Related Publications
CONTEXT: The polycystic ovary syndrome (PCOS) is the commonest endocrine abnormality in women of reproductive age.
OBJECTIVE: To determine the rate of hospital admissions for women with PCOS in Western Australian population in comparison to women without PCOS.
DESIGN: A population-based retrospective cohort study using data linkage in a statewide hospital morbidity database system.
SETTING: All hospitals within Western Australia.
PARTICIPANTS: A total of 2566 women with PCOS hospitalized from 1997-2011 and 25 660 randomly selected age-matched women without a PCOS diagnosis derived from the electoral roll.
MAIN OUTCOME MEASURES: Hospitalizations by ICD-10-M diagnoses from 15 years were compared.
RESULTS: Hospitalizations were followed until a median age of 35.8 years (interquartile range, 31.0-39.9). PCOS was associated with more nonobstetric and non-injury-related hospital admissions (median, 5 vs 2; P < .001), a diagnosis of adult-onset diabetes (12.5 vs 3.8%), obesity (16.0 vs 3.7%), hypertensive disorder (3.8 vs 0.7%), ischemic heart disease (0.8 vs 0.2%), cerebrovascular disease (0.6 vs 0.2%), arterial and venous disease (0.5 vs 0.2% and 10.4 vs 5.6%, respectively), asthma (10.6 vs 4.5%), stress/anxiety (14.0 vs 5.9%), depression (9.8 vs 4.3%), licit/illicit drug-related admissions (8.8 vs 4.5%), self-harm (7.2 vs 2.9%), land transport accidents (5.2 vs 3.8%), and mortality (0.7 vs 0.4%) (all P < .001). Women with PCOS had a higher rate of admissions for menorrhagia (14.1 vs 3.6%), treatment of infertility (40.9 vs 4.6%), and miscarriage (11.1 vs 6.1%) and were more likely to require in vitro fertilization (17.2 vs 2.0%).
CONCLUSION: PCOS has profound medical implications for the health of women, and health care resources should be directed accordingly.

Aye PS, Elwood JM, Stevanovic V
Comparison of cancer survival in New Zealand and Australia, 2006-2010.
N Z Med J. 2014; 127(1407):14-26 [PubMed] Related Publications
BACKGROUND AND AIMS: Previous studies have shown substantially higher mortality rates from cancer in New Zealand compared to Australia, but these studies have not included data on patient survival. This study compares the survival of cancer patients diagnosed in 2006-10 in the whole populations of New Zealand and Australia.
METHOD: Identical period survival methods were used to calculate relative survival ratios for all cancers combined, and for 18 cancers each accounting for more than 50 deaths per year in New Zealand, from 1 to 10 years from diagnosis.
RESULTS: Cancer survival was lower in New Zealand, with 5-year relative survival being 4.2% lower in women, and 3.8% lower in men for all cancers combined. Of 18 cancers, 14 showed lower survival in New Zealand; the exceptions, with similar survival in each country, being melanoma, myeloma, mesothelioma, and cervical cancer. For most cancers, the differences in survival were maximum at 1 year after diagnosis, becoming smaller later; however, for breast cancer, the survival difference increased with time after diagnosis.
CONCLUSION: The lower survival in New Zealand, and the higher mortality rates shown earlier, suggest that further improvements in recognition, diagnosis, and treatment of cancer in New Zealand should be possible. As the survival differences are seen soon after diagnosis, issues of early management in primary care and time intervals to diagnosis and treatment may be particularly important.

Bartelink H, Maingon P, Poortmans P, et al.
Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer: 20-year follow-up of a randomised phase 3 trial.
Lancet Oncol. 2015; 16(1):47-56 [PubMed] Related Publications
BACKGROUND: Since the introduction of breast-conserving treatment, various radiation doses after lumpectomy have been used. In a phase 3 randomised controlled trial, we investigated the effect of a radiation boost of 16 Gy on overall survival, local control, and fibrosis for patients with stage I and II breast cancer who underwent breast-conserving treatment compared with patients who received no boost. Here, we present the 20-year follow-up results.
METHODS: Patients with microscopically complete excision for invasive disease followed by whole-breast irradiation of 50 Gy in 5 weeks were centrally randomised (1:1) with a minimisation algorithm to receive 16 Gy boost or no boost, with minimisation for age, menopausal status, presence of extensive ductal carcinoma in situ, clinical tumour size, nodal status, and institution. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT02295033.
FINDINGS: Between May 24, 1989, and June 25, 1996, 2657 patients were randomly assigned to receive no radiation boost and 2661 patients randomly assigned to receive a radiation boost. Median follow-up was 17.2 years (IQR 13.0-19.0). 20-year overall survival was 59.7% (99% CI 56.3-63.0) in the boost group versus 61.1% (57.6-64.3) in the no boost group, hazard ratio (HR) 1.05 (99% CI 0.92-1.19, p=0.323). Ipsilateral breast tumour recurrence was the first treatment failure for 354 patients (13%) in the no boost group versus 237 patients (9%) in the boost group, HR 0.65 (99% CI 0.52-0.81, p<0.0001). The 20-year cumulative incidence of ipsilatelal breast tumour recurrence was 16.4% (99% CI 14.1-18.8) in the no boost group versus 12.0% (9.8-14.4) in the boost group. Mastectomies as first salvage treatment for ipsilateral breast tumour recurrence occurred in 279 (79%) of 354 patients in the no boost group versus 178 (75%) of 237 in the boost group. The cumulative incidence of severe fibrosis at 20 years was 1.8% (99% CI 1.1-2.5) in the no boost group versus 5.2% (99% CI 3.9-6.4) in the boost group (p<0.0001).
INTERPRETATION: A radiation boost after whole-breast irradiation has no effect on long-term overall survival, but can improve local control, with the largest absolute benefit in young patients, although it increases the risk of moderate to severe fibrosis. The extra radiation dose can be avoided in most patients older than age 60 years.
FUNDING: Fonds Cancer, Belgium.

Cuzick J, Sestak I, Cawthorn S, et al.
Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial.
Lancet Oncol. 2015; 16(1):67-75 [PubMed] Related Publications
BACKGROUND: Four previously published randomised clinical trials have shown that tamoxifen can reduce the risk of breast cancer in healthy women at increased risk of breast cancer in the first 10 years of follow-up. We report the long-term follow-up of the IBIS-I trial, in which the participants and investigators remain largely masked to treatment allocation.
METHODS: In the IBIS-I randomised controlled trial, premenopausal and postmenopausal women 35-70 years of age deemed to be at an increased risk of developing breast cancer were randomly assigned (1:1) to receive oral tamoxifen 20 mg daily or matching placebo for 5 years. Patients were randomly assigned to the two treatment groups by telephone or fax according to a block randomisation schedule (permuted block sizes of six or ten). Patients and investigators were masked to treatment assignment by use of central randomisation and coded drug supply. The primary endpoint was the occurrence of breast cancer (invasive breast cancer and ductal carcinoma in situ), analysed by intention to treat. Cox proportional hazard models were used to assess breast cancer occurrence and mortality. The trial is closed to recruitment and active treatment is completed, but long-term follow-up is ongoing. This trial is registered with controlledtrials.com, number ISRCTN91879928.
FINDINGS: Between April 14, 1992, and March 30, 2001, 7154 eligible women recruited from genetics clinics and breast care clinics in eight countries were enrolled into the IBIS-I trial and were randomly allocated to the two treatment groups: 3579 to tamoxifen and 3575 to placebo. After a median follow up of 16.0 years (IQR 14.1-17.6), 601 breast cancers have been reported (251 [7.0%] in 3579 patients in the tamoxifen group vs 350 [9.8%] in 3575 women in the placebo group; hazard ratio [HR] 0.71 [95% CI 0.60-0.83], p<0.0001). The risk of developing breast cancer was similar between years 0-10 (226 [6.3%] in 3575 women in the placebo group vs 163 [4.6%] in 3579 women in the tamoxifen group; hazard ratio [HR] 0.72 [95% CI 0.59-0.88], p=0.001) and after 10 years (124 [3.8%] in 3295 women vs 88 [2.6%] in 3343, respectively; HR 0.69 [0.53-0.91], p=0.009). The greatest reduction in risk was seen in invasive oestrogen receptor-positive breast cancer (HR 0.66 [95% CI 0.54-0.81], p<0.0001) and ductal carcinoma in situ (0.65 [0.43-1.00], p=0.05), but no effect was noted for invasive oestrogen receptor-negative breast cancer (HR 1.05 [95% CI 0.71-1.57], p=0.8).
INTERPRETATION: These results show that tamoxifen offers a very long period of protection after treatment cessation, and thus substantially improves the benefit-to-harm ratio of the drug for breast cancer prevention.
FUNDING: Cancer Research UK (UK) and the National Health and Medical Research Council (Australia).

Yu XQ, De Angelis R, Luo Q, et al.
A population-based study of breast cancer prevalence in Australia: predicting the future health care needs of women living with breast cancer.
BMC Cancer. 2014; 14:936 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Breast cancer places a heavy burden on the Australian healthcare system, but information about the actual number of women living with breast cancer and their current or future health service needs is limited. We used existing population-based data and innovative statistical methods to address this critical research question in a well-defined geographic region.
METHODS: Breast cancer data from the New South Wales (NSW) Central Cancer Registry and PIAMOD (Prevalence and Incidence Analysis MODel) software were used to project future breast cancer prevalence in NSW. Parametric models were fitted to incidence and survival data, and the modelled incidence and survival estimates were then used to estimate current and future prevalence. To estimate future healthcare requirements the projected prevalence was then divided into phases of care according to the different stages of the survivorship trajectory.
RESULTS: The number of women in NSW living with a breast cancer diagnosis had increased from 19,305 in 1990 to 48,754 in 2007. This number is projected to increase further to 68,620 by 2017. The majority of these breast cancer survivors will require continued monitoring (31,974) or will be long-term survivors (29,785). About 9% will require active treatment (either initial therapy, or treatment for subsequent metastases or second cancer) and 1% will need end of life care due to breast cancer.
CONCLUSIONS: Extrapolating these projections to the national Australian population would equate to 209,200 women living with breast cancer in Australia in 2017, many of whom will require active treatment or post-treatment monitoring. Thus, careful planning and development of a healthcare system able to respond to this increased demand is required.

Harding JL, Shaw JE, Peeters A, et al.
Cancer risk among people with type 1 and type 2 diabetes: disentangling true associations, detection bias, and reverse causation.
Diabetes Care. 2015; 38(2):264-70 [PubMed] Related Publications
OBJECTIVE: Evidence indicates an increased risk of certain cancers among people with type 2 diabetes. Evidence for rarer cancers and for type 1 diabetes is limited. We explored the excess risk of site-specific cancer incidence and mortality among people with type 1 and type 2 diabetes, compared with the general Australian population.
RESEARCH DESIGN AND METHODS: Registrants of a national diabetes registry (953,382) between 1997 and 2008 were linked to national death and cancer registries. Standardized incidence and mortality ratios (SIRs/SMRs) are reported.
RESULTS: For type 1 diabetes, significant elevated SIRs were observed for pancreas, liver, esophagus, colon and rectum (females only [F]), stomach (F), thyroid (F), brain (F), lung (F), endometrium, and ovary, and decreased SIRs were observed for prostate in males. Significantly increased SMRs were observed for pancreas, liver, and kidney (males only), non-Hodgkin's lymphoma, brain (F), and endometrium. For type 2 diabetes, significant SIRs were observed for almost all site-specific cancers, with highest SIRs observed for liver and pancreas, and decreased risks for prostate and melanoma. Significant SMRs were observed for liver, pancreas, kidney, Hodgkin's lymphoma, gallbladder (F), stomach (F), and non-Hodgkin's lymphoma (F). Cancer risk was significantly elevated throughout follow-up time but was higher in the first 3 months postregistration, suggesting the presence of detection bias and/or reverse causation.
CONCLUSIONS: Type 1 and type 2 diabetes are associated with an excess risk of incidence and mortality for overall and a number of site-specific cancers, and this is only partially explained by bias. We suggest that screening for cancers in diabetic patients is important.

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