Management and 5-year outcomes in 9938 women with screen-detected ductal carcinoma in situ: the UK Sloane Project.

BACKGROUND: Management of screen-detected ductal carcinoma in situ (DCIS) remains controversial. METHODS: A prospective cohort of patients with DCIS diagnosed through the UK National Health Service Breast Screening Programme (1st April 2003 to 31st March 2012) was linked to national databases and case note review to analyse patterns of care, recurrence and mortality. RESULTS: Screen-detected DCIS in 9938 women, with mean age of 60 years (range 46-87), was treated by mastectomy (2931) or breast conserving surgery (BCS) (7007; 70%). At 64 months median follow-up, 697 (6.8%) had further DCIS or invasive breast cancer after BCS (7.8%) or mastectomy (4.5%) (p < 0.001). Breast radiotherapy (RT) after BCS (4363/7007; 62.3%) was associated with a 3.1% absolute reduction in ipsilateral recurrent DCIS or invasive breast cancer (no RT: 7.2% versus RT: 4.1% [p < 0.001]) and a 1.9% absolute reduction for ipsilateral invasive breast recurrence (no RT: 3.8% versus RT: 1.9% [p < 0.001]), independent of the excision margin width or size of DCIS. Women without RT after BCS had more ipsilateral breast recurrences (p < 0.001) when the radial excision margin was <2 mm. Adjuvant endocrine therapy (1208/9938; 12%) was associated with a reduction in any ipsilateral recurrence, whether RT was received (hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.41-0.80) or not (HR 0.68; 95% CI 0.51-0.91) after BCS. Women who developed invasive breast recurrence had a worse survival than those with recurrent DCIS (p < 0.001). Among 321 (3.2%) who died, only 46 deaths were attributed to invasive breast cancer. CONCLUSION: Recurrent DCIS or invasive cancer is uncommon after screen-detected DCIS. Both RT and endocrine therapy were associated with a reduction in further events but not with breast cancer mortality within 5 years of diagnosis. Further research to identify biomarkers of recurrence risk, particularly as invasive disease, is indicated.

Modeling the Cost-Effectiveness of Alternative Upper Age Limits for Breast Cancer Screening in England and Wales.

BACKGROUND: Currently in the United Kingdom, the National Health Service (NHS) Breast Screening Programme invites all women for triennial mammography between the ages of 47 and 73 years (the extension to 47-50 and 70-73 years is currently examined as part of a randomized controlled trial). The benefits and harms of screening in women 70 years and older, however, are less well documented. OBJECTIVES: The aim of this study was to examine whether extending screening to women older than 70 years would represent a cost-effective use of NHS resources and to identify the upper age limit at which screening mammography should be extended in England and Wales. METHODS: A mathematical model that allows the impact of screening policies on cancer diagnosis and subsequent management to be assessed was built. The model has two parts: a natural history model of the progression of breast cancer up to discovery and a postdiagnosis model of treatment, recurrence, and survival. The natural history model was calibrated to available data and compared against published literature. The management of breast cancer at diagnosis was taken from registry data and valued using official UK tariffs. RESULTS: The model estimated that screening would lead to overdiagnosis in 6.2% of screen-detected women at the age of 72 years, increasing up to 37.9% at the age of 90 years. Under commonly quoted willingness-to-pay thresholds in the United Kingdom, our study suggests that an extension to screening up to the age of 78 years represents a cost-effective strategy. CONCLUSIONS: This study provides encouraging findings to support the extension of the screening program to older ages and suggests that further extension of the UK NHS Breast Screening Programme up to age 78 years beyond the current upper age limit of 73 years could be potentially cost-effective according to current NHS willingness-to-pay thresholds.

Impact of deprivation on breast cancer survival among women eligible for mammographic screening in the West Midlands (UK) and New South Wales (Australia): Women diagnosed 1997-2006.

Women diagnosed with breast cancer in the UK display marked differences in survival between categories defined by socio-economic deprivation. Timeliness of diagnosis is one of the possible explanations for these patterns. Women whose cancer is screen-detected are more likely to be diagnosed at an earlier stage. We examined deprivation and screening-specific survival in order to evaluate the role of early diagnosis upon deprivation-specific survival differences in the West Midlands (UK) and New South Wales (Australia). We estimated net survival for women aged 50-65 years at diagnosis and whom had been continuously eligible for screening from the age of 50. Records for 5,628 women in West Midlands (98.5% of those eligible, mean age at diagnosis 53.7 years) and 6,396 women in New South Wales (99.9% of those eligible, mean age at diagnosis 53.8 years). In New South Wales, survival was similar amongst affluent and deprived women, regardless of whether their cancer was screen-detected or not. In the West Midlands, there were large and persistent differences in survival between affluent and deprived women. Deprivation differences were similar between the screen-detected and non-screen detected groups. These differences are unlikely to be solely explained by artefact, or by patient or tumour factors. Further investigations into the timeliness and appropriateness of the treatments received by women with breast cancer across the social spectrum in the UK are warranted.

Are international differences in breast cancer survival between Australia and the UK present amongst both screen-detected women and non-screen-detected women? survival estimates for women diagnosed in West Midlands and New South Wales 1997-2006.

We examined survival in screened-detected and non-screen-detected women diagnosed in the West Midlands (UK) and New South Wales (Australia) in order to evaluate whether international differences in survival are related to early diagnosis, or to other factors relating to the healthcare women receive. Data for women aged 50 - 65 years who had been eligible for screening from 50 years were examined. Data for 5,628 women in West Midlands and 6,396 women in New South Wales were linked to screening service records (mean age at diagnosis 53.7 years). We estimated net survival and modelled the excess hazard ratio of breast cancer death by screening status. Survival was lower for women in the West Midlands than in New South Wales (5-year net survival 90.9% [95% CI 89.9%-91.7%] compared with 93.4% [95% CI 92.6%-94.1%], respectively). The difference was greater between the two populations of non-screen-detected women (4.9%) compared to between screen-detected women, (1.8% after adjustment for lead-time and over-diagnosis). The adjusted excess hazard ratio of breast cancer death for West Midlands compared with New South Wales was greater in the non-screen-detected group (EHR 2.00, 95% CI 1.70 - 2.31) but not significantly different to that for women whose cancer had been screen-detected (EHR 1.72, 95% CI 0.87 - 2.56). In this study more than one in three breast cancer deaths in the West Midlands would have been avoided if survival had been the same as in New South Wales. The possibility that women in the UK receive poorer treatment is an important potential explanation which should be examined with care.

Incidence and survival of gynecologic sarcomas in England.

OBJECTIVE: Gynecologic sarcomas account for approximately 3% to 4% of all gynecologic malignancies and are associated with poor outcomes compared with gynecologic carcinomas. The aim of this study is to report the incidence and survival rates of the main gynecologic sarcomas using national English cancer registration data. METHODS/MATERIALS: Records of gynecologic sarcomas diagnosed between 1985 and 2008 were extracted from the English National Cancer Data Repository. ICD-O3 morphology codes were used to assign tumor records to specific histologic subgroups. Incidence and 5-year relative survival rates were calculated. RESULTS: There were 5316 new cases of gynecologic sarcoma diagnosed in England between 1985 and 2008. Incidence rates increased significantly in the early 1990s, probably due to coding changes. Age-specific incidence rates were highest in women aged between 45 and 64 years. In the most recent period studied (2001-2008), incidence rates fluctuated between 8 and 9.6 per million. The most common anatomical site was the uterus (83% of all diagnoses), and the most common histologic diagnosis was leiomyosarcoma (52% of all diagnoses). Overall 5-year relative survival increased significantly between 1985-1989 and 2000-2004, from 34% to 48%. CONCLUSIONS: Gynecologic sarcoma incidence rates have varied little since 1993, whereas survival has improved significantly. These results are consistent with previously published small series and case studies, and provide a more complete picture of gynecologic sarcoma incidence and survival patterns in England.

Identifying prognostic indicators in staging metastatic sarcomas using hospital episode statistics.

Detailed staging data are currently not available for sarcoma patients. This paper uses Hospital Episodes Statistics (HES) data to identify patients with Stage IV disease at diagnosis. Cancer patients with a record of metastasis at diagnosis were identified by combining HES data with National Cancer Data Repository data. The presence of metastases at diagnosis varied with age, sarcoma morphological sub-type, and anatomical location. Survival rates for patients with metastases were significantly lower than for those without metastases. Although not a perfect substitute for detailed staging information, the method described provides a good proxy to identify patients with Stage IV disease.

Validation of death prediction after breast cancer relapses using joint models.

BACKGROUND: Cancer relapses may be useful to predict the risk of death. To take into account relapse information, the Landmark approach is popular. As an alternative, we propose the joint frailty model for a recurrent event and a terminal event to derive dynamic predictions of the risk of death. METHODS: The proposed prediction settings can account for relapse history or not. In this work, predictions developed on a French hospital series of patients with breast cancer are externally validated on UK and Netherlands registry data. The performances in terms of prediction error and calibration are compared to those from a Landmark Cox model. RESULTS: The error of prediction was reduced when relapse information was taken into account. The prediction was well-calibrated, although it was developed and validated on very different populations. Joint modelling and Landmark approaches had similar performances. CONCLUSIONS: When predicting the risk of death, accounting for relapses led to better prediction performance. Joint modelling appeared to be suitable for such prediction. Performance was similar to the landmark Cox model, while directly quantifying the correlation between relapses and death.

Adverse surgical outcomes in screen-detected ductal carcinoma in situ of the breast.

BACKGROUND: The Sloane Project is the largest prospective audit of ductal carcinoma in situ (DCIS) worldwide, with over 12,000 patients registered between 2003 and 2012, accounting for 50% of screen-detected DCIS diagnosed in the United Kingdom (UK) over the period of accrual. METHODS: Complete multidisciplinary data from 8313 patients with screen-detected DCIS were analysed for surgical outcome in relation to key radiological and pathological parameters for the cohort and also by hospital of treatment. Adverse surgical outcomes were defined as either failed breast conservation surgery (BCS) or mastectomy for small lesions (<20mm) (MFSL). Inter-hospital variation was analysed by grouping hospitals into high, medium and low frequency subgroups for these two adverse outcomes. RESULTS: Patients with failed BCS or MFSL together accounted for 49% of all mastectomies. Of 6633 patients embarking on BCS, 799 (12.0%) required mastectomy. MFSL accounted for 510 (21%) of 2479 mastectomy patients. Failed BCS was associated with significant radiological under-estimation of disease extent and MFSL significant radiological over-estimation of disease extent. There was considerable and significant inter-hospital variation in failed BCS (range 3-32%) and MFSL (0-60%) of a hospital's BCS/mastectomy workload respectively. Conversely, there were no differences between the key radiological and pathological parameters in high, medium and low frequency adverse-outcome hospitals. CONCLUSIONS: This evidence suggests significant practice variation, not patient factors, is responsible for these adverse surgical outcomes in screen-detected DCIS. The Sloane Project provides an evidence base for future practice benchmarking.

Time to begin adjuvant chemotherapy and survival in breast cancer patients: a retrospective observational study using latent class analysis.

The analysis of time to treatment data and the evaluation of subsequent effects on health outcomes can be complex due to the nature of the data and the relationships amongst the variables. This study proposes an alternative method of analyzing such data using latent class analysis (LCA). The association between time to begin adjuvant chemotherapy after breast cancer surgery and survival was investigated using both "traditional" regression analysis and LCA. Women with breast cancer undergoing surgery and subsequent adjuvant chemotherapy in two English regions between January 01, 1998 and December 31, 2004 were identified from a linked cancer registry-Hospital Episode Statistics dataset (n = 10,366). Patient, tumor, and treatment information were extracted. A Cox proportional hazards model was used to analyze 5-year survival using regression analysis and LCA. Using "traditional" regression analysis, women beginning chemotherapy >10 weeks after surgery had worse survival in region 1 (HR = 1.49, 95% CI 1.13-1.95 compared to <3 weeks) but not region 2. LCA split the women into three groups representing short, medium, and long waits. The median time to begin chemotherapy in the "long" wait group was 70 (region 1) and 57 (region 2) days. In this group, increased time to begin chemotherapy was associated with worse survival (region 1 HR = 1.15, 95% CI 1.11-1.18; region 2 HR = 1.08, 95% CI 1.03-1.13 per week increase). LCA identified a group of 13-15% of women for whom a longer time to begin chemotherapy had an adverse effect on survival. This methodology provides an excellent framework in which to examine complex associations between the delivery of patient care and patient outcomes.

Surgeon and breast unit volume-outcome relationships in breast cancer surgery and treatment.

OBJECTIVES: To determine whether surgeon case volume and Unit case volume affected specific recognized key performance indicators (KPIs) of breast cancer surgical management. BACKGROUND: An increasing body of evidence suggests that a higher standard of cancer care, demonstrated by improved outcomes, is provided in high-volume units or by high-volume surgeons. The volume-outcome relationship pertaining to screen-detected breast cancers has yet to be thoroughly established and remains a pertinent issue in view of the debate surrounding breast cancer screening. METHODS: The study population comprised all women with a new screen diagnosed breast cancer between 2004-2005 and 2009-2010. Surgeons' mean annual patient volumes were calculated and grouped as very low (<5), low (5-15), medium (16-49), or high volume (>50). The effect of breast screening unit volume was also evaluated. Statistical analyses were performed using Minitab V16.0 software (State College, PA) and R V2.13.0. RESULTS: There were 81,416 patients aged 61 (±6.8) years treated by 682 surgeons across 82 units. There were 209 very low-, 126 low-, 295 medium-, and 51 high-volume surgeons. The proportion of patients managed by very low-, low-, medium-, and high-volume surgeons was 1.2%, 6.9%, 65.5%, and 25.7%, respectively. Patients managed by high-volume surgeons were more likely to have breast-conserving surgery (BCS) than those managed by low-volume surgeons (P < 0.001). There was a higher proportion of sentinel lymph node biopsies (SLNB) performed by high-volume surgeons in invasive cancers (P = 0.005). High-volume units performed more BCS and SLNB than low-volume units (P < 0.001 and P < 0.001, respectively). CONCLUSIONS: Even in a setting with established quality control measures (KPIs) surgeon and unit volume have potent influences on initial patient management and treatment.

Prospective observational study of breast cancer treatment outcomes for UK women aged 18-40 years at diagnosis: the POSH study.

BACKGROUND: Breast cancer at a young age is associated with poor prognosis. The Prospective Study of Outcomes in Sporadic and Hereditary Breast Cancer (POSH) was designed to investigate factors affecting prognosis in this patient group. METHODS: Between 2000 and 2008, 2956 patients aged 40 years or younger were recruited to a UK multicenter prospective observational cohort study (POSH). Details of tumor pathology, disease stage, treatment received, and outcome were recorded. Overall survival (OS) and distant disease-free interval (DDFI) were assessed using Kaplan-Meier curves. All statistical tests were two-sided. RESULTS: Median age of patients was 36 years. Median tumor diameter was 22 mm, and 50% of patients had positive lymph nodes; 59% of tumors were grade 3, 33.7% were estrogen receptor (ER) negative, and 24% were human epidermal growth factor receptor 2 (HER2) positive. Five-year OS was higher for patients with ER-positive than ER-negative tumors (85.0%, 95% confidence interval [CI] = 83.2% to 86.7% vs 75.7%, 95% CI = 72.8% to 78.4%; P < .001), but by eight years, survival was almost equal. The eight-year OS of patients with ER-positive tumors was similar to that of patients with ER-negative tumors in both HER2-positive and HER2-negative subgroups. The flexible parametric survival model for OS shows that the risk of death increases steadily over time for patients with ER-positive tumors in contrast to patients with ER-negative tumors, where risk of death peaked at two years. CONCLUSIONS: These results confirm the increased frequency of ER-negative tumors and early relapse in young patients and also demonstrate the equally poor longer-term outlook of young patients who have ER-positive tumors with HER2-negative or -positive disease.

Are symptomatic guidelines for chemotherapy appropriate to ER-positive screen-detected breast cancer (SDBC)?

Oncologists recommend chemotherapy to postmenopausal women with adverse prognostic factors, but predictors of the benefit of chemotherapy are mainly based on mortality from symptomatic cancer trials. From 1990 to 1998, 1475 breast cancers (875 screen detected cancers [SDBCs]: 600 symptomatic) were treated in women aged 50-65 years and prognostic factors compared with cancer mortality. Median follow-up was 110 months. The Nottingham Prognostic Index (NPI) was calculated for 6737 breast cancers which were part of the Association of Breast Surgery (ABS) 2001/2002 Audit of SDBCs to validate survival figures. Ten year survival was 92.1% for SDBC and 77.6% for symptomatic cancers. Adjusting for baseline factors, SDBCs had a reduced mortality (RR = 0.42 (0.31-0.57), independent of grade, node status and tumour size. Oestrogen receptor (ER) positive SDBC had a lower annual mortality rate (0.6%) compared with symptomatic (4.3%: P < 0.001) or ER negative SDBC (1.8%). Epithelial proliferation was lower in SDBC in all NPI groups compared with symptomatic cancers (P ≤ 0.001). Grade, node status, ER status, size and mode of detection predicted survival. Survival for each NPI group was better for SDBC. For ER positive SDBC in the Moderate Prognostic Group 1 (MPG1), 10 year mortality was 6.4% compared with 17.6% in symptomatic (P = 0.001). NPI on 6,737 operable SDBC confirmed similar mortality in all groups (4% mortality in MPG1 group). SDBC have lower mortality than symptomatic due to a lower proliferative index. The use of adjuvant chemotherapy is over-treatment for ER positive SDBCs with Good Prognostic Group (GPG) and MPG1 NPI scores.

Impact of the UK colorectal cancer screening pilot studies on incidence, stage distribution and mortality trends.

OBJECTIVE: To assess the impact of the UK colorectal cancer guaiac faecal occult blood test screening pilot studies on incidence trends, stage distribution and mortality trends. DESIGN: Ecological study. SETTING: Scotland and the West Midlands. DATA: We extracted anonymised colorectal cancer (ICD-10 C18-C20) registration (1982-2006) and death records (1982-2007), along with corresponding mid-year population estimates. INTERVENTION: Residents of the screening pilot areas, in the age group 50-69 years, were offered biennial guaiac faecal occult blood test screening from 2000 onwards. Screening was not offered routinely in non-pilot areas until the start of the roll-out of the national screening programmes in England and in Scotland in 2006 and 2007, respectively. MAIN OUTCOME MEASURES: We analysed trends in age-specific incidence and mortality rates, and Dukes' stage distribution. Within each country/region, we compared the screening pilot areas to non-screening pilot ('control') areas using Chi square tests and Poisson regression modelling. RESULTS: Following the start of the screening pilots, as expected in the prevalent round of a new screening programme, in the pilot areas there was a short-lived increase in incidence of colorectal cancer among 50-69 year olds except for females in the West Midlands. A trend towards earlier stage and less advanced disease was also observed, with males showing significant increases in Dukes' A and corresponding decreases in Dukes' C in the screening pilot areas (all P < 0.03). With the exception of females in the West Midlands, mortality rates for colorectal cancer decreased significantly and at a faster rate in the populations invited for screening. CONCLUSION: The existence of a natural control population not yet invited for screening provided a unique opportunity to assess whether the benefits of colorectal cancer screening, beyond the setting of a randomised controlled trial, could be detected using routinely collected statistics. Our analysis suggests that screening will fulfil its aim of reducing mortality from colorectal cancer.

Use of name recognition software, census data and multiple imputation to predict missing data on ethnicity: application to cancer registry records.

BACKGROUND: Information on ethnicity is commonly used by health services and researchers to plan services, ensure equality of access, and for epidemiological studies. In common with other important demographic and clinical data it is often incompletely recorded. This paper presents a method for imputing missing data on the ethnicity of cancer patients, developed for a regional cancer registry in the UK. METHODS: Routine records from cancer screening services, name recognition software (Nam Pehchan and Onomap), 2001 national Census data, and multiple imputation were used to predict the ethnicity of the 23% of cases that were still missing following linkage with self-reported ethnicity from inpatient hospital records. RESULTS: The name recognition software were good predictors of ethnicity for South Asian cancer cases when compared with data on ethnicity derived from hospital inpatient records, especially when combined (sensitivity 90.5%; specificity 99.9%; PPV 93.3%). Onomap was a poor predictor of ethnicity for other minority ethnic groups (sensitivity 4.4% for Black cases and 0.0% for Chinese/Other ethnic groups). Area-based data derived from the national Census was also a poor predictor non-White ethnicity (sensitivity: South Asian 7.4%; Black 2.3%; Chinese/Other 0.0%; Mixed 0.0%). CONCLUSIONS: Currently, neither method for assigning individuals to an ethnic group (name recognition and ethnic distribution of area of residence) performs well across all ethnic groups. We recommend further development of name recognition applications and the identification of additional methods for predicting ethnicity to improve their precision and accuracy for comparisons of health outcomes. However, real improvements can only come from better recording of ethnicity by health services.

Evidence against the proposition that "UK cancer survival statistics are misleading": simulation study with National Cancer Registry data.

OBJECTIVES: To simulate each of two hypothesised errors in the National Cancer Registry (recording of the date of recurrence of cancer, instead of the date of diagnosis, for registrations initiated from a death certificate; long term survivors who are never notified to the registry), to estimate their possible effect on relative survival, and to establish whether lower survival in the UK might be due to one or both of these errors. DESIGN: Simulation study. SETTING: National Cancer Registry of England and Wales. Population Patients diagnosed as having breast (women), lung, or colorectal cancer during 1995-2007 in England and Wales, with follow-up to 31 December 2007. MAIN OUTCOME MEASURE: Mean absolute percentage change in one year and five year relative survival associated with each simulated error. RESULTS: To explain the differences in one year survival after breast cancer between England and Sweden, under the first hypothesis, date of diagnosis would have to have been incorrectly recorded by an average of more than a year for more than 70% of women known to be dead. Alternatively, under the second hypothesis, failure to register even 40% of long term survivors would explain less than half the difference in one year survival. Results were similar for lung and colorectal cancers. CONCLUSIONS: Even implausibly extreme levels of the hypothesised errors in the cancer registry data could not explain the international differences in survival observed between the UK and other European countries.

Using routinely collected health data to investigate the association between ethnicity and breast cancer incidence and survival: what is the impact of missing data and multiple ethnicities?

OBJECTIVES: The aims of this study were to: (1) investigate the relationship between ethnicity and breast cancer incidence and survival using cancer registry and Hospital Episode Statistics (HES) data; and (2) assess the impact of missing data and the recording of multiple ethnicities for some patients. DESIGN: A total of 48,234 breast cancer patients diagnosed between 1997 and 2003 in two English regions were identified. Ethnicity was missing in 16% of cases. Multiple imputation (10 iterations) of missing ethnicity was undertaken using a range of predictor variables. Multiple ethnicities for a single patient were recorded in 4% of cases. Three methods of assigning ethnicity were used: 'most popular' code, 'last recorded' code, and proportions calculated using all recorded episodes for each patient. Age-standardised incidence rate ratios (IRR) and 5-year survival were calculated before and after imputation for the three methods of assigning ethnicity. RESULTS: Breast cancer incidence was lower in the South Asian group (IRR=0.59, 95% confidence interval [CI] 0.51-0.69 compared to the White group). In unadjusted analyses, the South Asian group had consistently higher survival compared with the White group (hazard ratio [HR]=0.81, 95% CI 0.68-0.95). After adjustment for age and stage, there were no survival differences amongst the White, South Asian and Black groups. Survival was higher in the 'Other' ethnic group when using the 'last recorded' method to assign ethnicity (HR=0.62, 95% CI 0.45-0.85 compared with the White group). The results were similar before and after imputation, using all three methods of assigning ethnicity. CONCLUSIONS: Breast cancer incidence was lower in the South Asian group than in the White group. After adjusting for casemix there were no consistent survival differences amongst the ethnic groups. Although the impact of missing data and multiple ethnicities was minimal in this study, researchers should always consider these issues, as the results may not be generalisable to other populations and datasets.

Prognosis and pathology of screen-detected carcinomas: how different are they?

BACKGROUND: It has been observed that screen-detected breast cancers have a better prognosis than symptomatic tumors, even after taking pathological tumor attributes into account. This has led to the hypothesis that screen-detected tumors are substantially biologically different from symptomatic cancers. METHODS: The pathology and survival by detection mode was investigated in 21,382 breast cancers diagnosed in women aged 50-64 years in the West Midlands, United Kingdom, between 1988 and 2004. Tumor attributes were compared using chi-square tests and logistic regression. Survival was analyzed using Cox regression. RESULTS: Screen-detected cancers were significantly smaller, better differentiated, and less likely to be node-positive than symptomatic cancers (P < .001 in all cases). In addition, a higher proportion of screen-detected cancers were hormone receptor-positive, and a higher proportion were tubular carcinomas (P < .001). Survival was substantially better in screen-detected breast cancers (86% at 10 yearsvs 70% for interval cancers and 58% for cancers in women unexposed to screening). Adjustment for age, tumor size, nodal status, grade, histological type, and year of diagnosis accounted for 64% (interval cancers) and 68% (unexposed women) of these survival differences, respectively. Overall survival improved with time. Approximately half of this improvement was due to the increase over time in the proportion of tumors that were screen-detected. CONCLUSION: The majority of the difference in prognosis between screen-detected and symptomatic breast cancers is due to the differences in routinely measured pathological features (size, type, grade, and nodal status), leaving a small residual difference to be accounted for by other biological differences.

PREDICT: a new UK prognostic model that predicts survival following surgery for invasive breast cancer.

INTRODUCTION: The aim of this study was to develop and validate a prognostication model to predict overall and breast cancer specific survival for women treated for early breast cancer in the UK. METHODS: Using the Eastern Cancer Registration and Information Centre (ECRIC) dataset, information was collated for 5,694 women who had surgery for invasive breast cancer in East Anglia from 1999 to 2003. Breast cancer mortality models for oestrogen receptor (ER) positive and ER negative tumours were derived from these data using Cox proportional hazards, adjusting for prognostic factors and mode of cancer detection (symptomatic versus screen-detected). An external dataset of 5,468 patients from the West Midlands Cancer Intelligence Unit (WMCIU) was used for validation. RESULTS: Differences in overall actual and predicted mortality were <1% at eight years for ECRIC (18.9% vs. 19.0%) and WMCIU (17.5% vs. 18.3%) with area under receiver-operator-characteristic curves (AUC) of 0.81 and 0.79 respectively. Differences in breast cancer specific actual and predicted mortality were <1% at eight years for ECRIC (12.9% vs. 13.5%) and <1.5% at eight years for WMCIU (12.2% vs. 13.6%) with AUC of 0.84 and 0.82 respectively. Model calibration was good for both ER positive and negative models although the ER positive model provided better discrimination (AUC 0.82) than ER negative (AUC 0.75). CONCLUSIONS: We have developed a prognostication model for early breast cancer based on UK cancer registry data that predicts breast cancer survival following surgery for invasive breast cancer and includes mode of detection for the first time. The model is well calibrated, provides a high degree of discrimination and has been validated in a second UK patient cohort.

Differences in breast cancer incidence in Australia and England by age, extent of disease and deprivation status: women diagnosed 1980-2002.

OBJECTIVE: To compare breast cancer incidence in England and Australia by age, extent of disease and deprivation. METHODS: We analysed data for women aged 15-99 years diagnosed with breast cancer in England or Australia during the period 1990 to 1994, and in West Midlands or New South Wales during the period 1980 to 2002. We calculated three-year rolling average incidence rates and incidence rate ratios (IRR) between West Midlands and New South Wales by age, extent of disease and category of deprivation. RESULTS: Breast cancer incidence was higher in England than in Australia, and in West Midlands than in New South Wales but became more similar over time. Socio-economic differences in incidence were greater in New South Wales than in West Midlands. The most deprived women in West Midlands were diagnosed at a later stage of disease than the most deprived women in New South Wales. Incidence among elderly women was higher in West Midlands than in New South Wales. There were also high proportions of tumours with unknown stage among elderly women in West Midlands. CONCLUSIONS: Although the overall incidence of breast cancer is similar, differences by age, extent of disease and deprivation exist. IMPLICATIONS: The underlying reasons for these patterns require further examination.

Changes in and predictors of length of stay in hospital after surgery for breast cancer between 1997/98 and 2004/05 in two regions of England: a population-based study.

BACKGROUND: Decreases in length of stay (LOS) in hospital after breast cancer surgery can be partly attributed to the change to less radical surgery, but many other factors are operating at the patient, surgeon and hospital levels. This study aimed to describe the changes in and predictors of length of stay (LOS) in hospital after surgery for breast cancer between 1997/98 and 2004/05 in two regions of England. METHODS: Cases of female invasive breast cancer diagnosed in two English cancer registry regions were linked to Hospital Episode Statistics data for the period 1st April 1997 to 31st March 2005. A subset of records where women underwent mastectomy or breast conserving surgery (BCS) was extracted (n = 44,877). Variations in LOS over the study period were investigated. A multilevel model with patients clustered within surgical teams and NHS Trusts was used to examine associations between LOS and a range of factors. RESULTS: Over the study period the proportion of women having a mastectomy reduced from 58% to 52%. The proportion varied from 14% to 80% according to NHS Trust. LOS decreased by 21% from 1997/98 to 2004/05 (LOSratio = 0.79, 95%CI 0.77-0.80). BCS was associated with 33% shorter hospital stays compared to mastectomy (LOSratio = 0.67, 95%CI 0.66-0.68). Older age, advanced disease, presence of comorbidities, lymph node excision and reconstructive surgery were associated with increased LOS. Significant variation remained amongst Trusts and surgical teams. CONCLUSION: The number of days spent in hospital after breast cancer surgery has continued to decline for several decades. The change from mastectomy to BCS accounts for only 9% of the overall decrease in LOS. Other explanations include the adoption of new techniques and practices, such as sentinel lymph node biopsy and early discharge. This study has identified wide variation in practice with substantial cost implications for the NHS. Further work is required to explain this variation.