Abstract Key words: DCIS, radiotherapy, endocrine therapy, survival, surgical margins Background: The benefits and risks of breast screening remain controversial, with particular concern that ductal carcinoma in situ (DCIS) may be over-diagnosed and over-treated. There is little prospective data on treatment or outcomes for screen detected DCIS. Methods: A prospective cohort of non-invasive lesions diagnosed through the United Kingdom National Health Service Breast Screening Programme (NHSBSP) (1 April 2003 to 31 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 was analysed, 33% (9938/30041) of women with a final diagnosis of non-invasive breast neoplasia diagnosed through the NHSBSP over the same time. The patients (mean age was 60 years: range 46-87 years) were treated by breast conservation surgery (BCS; 7007; 70.5%) or mastectomy (2931). 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) and 228 women (2.3%) developed contralateral malignancy. Breast radiotherapy (RT) after BCS (4363/7007; 62%) was associated with a 3.1% absolute reduction in any ipsilateral DCIS or invasive cancer (No RT: 7.2% vs RT: 4.1% (p<0.001) and a 1.9% absolute reduction for ipsilateral invasive breast recurrence (No RT: 3.8% vs RT: 1.9% (p<0.001), independent of excision margin width or size of DCIS. Women who did not receive RT after BCS had more ipsilateral events (p=0.008) when the radial excision margin was <2mm. RT was rarely used after mastectomy for DCIS (33 women). Adjuvant endocrine therapy (prescribed for 1208/9938; 12.2%) was associated with a reduction in any ipsilateral recurrence, independent of whether women did (HR 0.57: 95% CI 0.41 - 0.80) or did not (HR 0.68: 95% CI 0.51 - 0.91) receive RT after BCS. Among 321 (3.2%) women who died, 46 deaths (0.5%; 14.3% of all deaths) were attributed to invasive breast cancer. Death from breast cancer was uncommon and outnumbered 5:1 by death due to other causes. RT after BCS was associated with a non-significant 0.2% absolute reduction in breast cancer mortality. However, women who developed invasive breast cancer had a worse survival than those with further DCIS (p<0.001). Conclusions: Recurrent DCIS or invasive cancer is uncommon following screen detected DCIS treated by surgery and adjuvant therapy. Both RT and endocrine therapy following surgery were associated with a significant reduction in further DCIS and invasive disease, but not breast cancer mortality, within 5 years of diagnosis. This study quantifies the benefits of radiotherapy and endocrine therapy to inform decision making in the management of screen detected DCIS. Citation Format: Thompson AM, Clements K, Cheung S, Pinder SE, Lawrence G, Sawyer E, Kearins O, Ball GR, Tomlinson I, Hanby AM, Thomas J, Maxwell AJ, Wallis MG, Dodwell DJ. Impact of radiotherapy and endocrine therapy on further events: Final multivariate analysis of a prospective, national cohort study of screen detected ductal carcinoma in situ (DCIS) of the breast [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-15-02.

Background: Understanding the route to diagnosis for patients with cancer is important to improve the diagnostic pathway and therefore outcomes. We aimed to investigate routes to diagnosis for patients with sarcoma in England.Methods: National patient level datasets relating to 7716 soft tissue and 1240 bone sarcoma patients diagnosed between 2006 and 2008 were analysed. Routes to diagnosis were defined as: "Two Week Wait Referral", "GP Referral", "Other Outpatient", "Inpatient Elective", "Emergency Presentation", "Death Certificate Only" and "Unknown".Results: Patients with sarcoma are most likely to be diagnosed after "GP Referral" or "Emergency Presentation" and are less likely to be referred under a two week wait compared with other malignancies. Patients with bone sarcoma under 10 or over 80 years of age were more likely to present by emergency routes, as were patients with vertebral column, pelvis or unspecified site tumours and those with Ewing's sarcoma or sarcoma NOS. Patients with soft tissue sarcoma under 19 or over 80 years of age and patients with GI tract tumours were more likely to present by emergency routes. Patients presenting by emergency routes more often had metastases and had lower 1 year survival. Patients from least deprived quintiles more often presented by unknown routes: those from more deprived quintiles more often presented by emergency routes.Conclusion: Routes to diagnosis for sarcoma patients differ from other cancers. Interventions to improve the diagnostic experience should consider the very young and elderly, tumours in abdominal, pelvic or spinal locations and on reducing emergency presentations. Crown Copyright (C) 2015 Published by Elsevier Ltd. All rights reserved.

BACKGROUND:Non-surgical management of older women with oestrogen receptor (ER)-positive operable breast cancer is common in the UK, with up to 40 per cent of women aged over 70 years receiving primary endocrine therapy. Although this may be appropriate for frailer patients, for some it may result in treatment failure, contributing to the poor outcomes seen in this age group. Wide variation in the rates of non-operative management of breast cancer in older women exists across the UK. Case mix may explain some of this variation in practice. METHODS:Data from two UK regional cancer registries were analysed to determine whether variation in treatment observed between 2002 and 2010 at hospital and clinician level persisted after adjustment for case mix. Expected case mix-adjusted surgery rates were derived by logistic regression using the variables age, proxy Charlson co-morbidity score, deprivation quintile, method of cancer detection, tumour size, stage, grade and node status. RESULTS:Data on 17,129 women aged 70 years or more with ER-positive operable breast cancer were analysed. There was considerable variation in rates of surgery at both hospital and clinician level. Despite adjusting for case mix, this variation persisted at hospital level, although not at clinician level. CONCLUSION:This study demonstrates variation in selection criteria for older women for operative treatment of early breast cancer, indicating that some older women may be undertreated or overtreated, and may partly explain the inferior disease outcomes in this age group. It emphasizes the urgent need for evidence-based guidelines for treatment selection criteria in older women with breast cancer.

Background: A role for radiotherapy after mastectomy for ductal carcinoma in situ (DCIS) is unclear. Using a prospective audit of DCIS detected through the NHS Breast Screening Programme we sought to determine a rationale for the use of post mastectomy radiotherapy for DCIS.Methods: Over a nine year period, from 9972 patients with screen-detected DCIS and complete surgical, pathology, radiotherapy and follow up data, 2944 women underwent mastectomy for DCIS of whom 33 (1.1%) received radiotherapy.Results: Use of post mastectomy radiotherapy was significantly associated with a close (<1 mm) pathology margin (chi(2)(1) 95.81; p < 0.00001), DCIS size (chi(2) (3) 16.96; p < 0.001) and the presence of microinvasion (chi(2)(1) 3.92; p < 0.05). At a median follow up 61 months, no woman who received radiotherapy had an ipsilateral further event, and only 1/33 women (3.0%) had a contralateral event. Of the women known not to have had radiotherapy post mastectomy, 45/2894 (1.6%) had an ipsilateral further event and 83 (2.9%) had a contralateral event.Conclusion: Recurrence following mastectomy for DCIS is rare. A close (<1 mm) margin, large tumour size and rnicroinvasion, may merit radiotherapy to reduce ipsilateral recurrence. (C) 2015 Elsevier Ltd. All rights reserved.

The National Bowel Cancer Screening Programme (NBCSP) was introduced in the West Midlands in 2006. Studies, including the UK Bowel Cancer Screening Pilot, have reported an 18% reduction in mortality. This regional study assesses the impact of screening on elective and emergency colorectal cancer (CRC) surgery.

Background: Older women are less likely to have surgery for operable breast cancer. This population-based study examines operation rates by age and identifies groups which present with early or late disease.Methods: 37 000 cancer registrations for 2007 were combined with Hospital Episode Statistics comorbidity data for England. Operation rates were examined by age, ethnicity, deprivation, comorbidity, screen-detection, tumour size, grade and nodal status. Early and late presentation were correlated with Nottingham Prognostic Index (NPI) groups and tumour size.Results: The proportion of women not having surgery increased from 7-10% at ages 35-69 to 82% from age 90. From age 70, the proportion not having surgery rose by an average of 3.1% per year of age. Women with a Charlson Comorbidity Index score of >= 1 (which increased with age), with tumours >50 mm or who were node positive, were less likely to have surgery. Although women aged 70-79 were more likely to have larger tumours, their tumours were also more likely to have an excellent or good NPI (p < 0.001). Good prognosis tumours were more likely to be screen-detected, and less likely in women aged 0-39, the deprived and,certain ethnic groups (p < 0.02).Conclusions: From age 70 there is an increasing failure to operate for breast cancer. Younger women and certain ethnic groups presented with more advanced tumours. Older women had larger tumours which were otherwise of good prognosis, and this would not account for the failure to operate which may in part be related to comorbidity in this age group. (C) 2014 Elsevier Ltd. All rights reserved.

Background: A third of breast cancers are diagnosed in women aged ≥70, yet this group is severely under-represented in clinical studies. As a result there is limited evidence to guide appropriate treatment selection for elderly breast cancer patients.

The diagnosis and surgical management of screen-detected Ductal Carcinoma In Situ (DCIS) remains controversial including a range of axillary approaches and consequent morbidity. This study examined the management of the axilla in all patients with DCIS presenting through the United Kingdom National Health Service Breast Screening Programme (UK NHS BSP). Retrospective analysis of the UK NHS BSP identified 26,696 women initially diagnosed with DCIS over the 8 years 1 April 2003-31 March 2011. The final breast pathology of these women was upgraded to invasive ductal cancer in 5564 (20.8%) women or micro-invasive cancer in 1031 (3.9%) women. At first operation, 5290 (26.3%) of the 20,094 women who had a final post-operative diagnosis of DCIS only underwent axillary surgery (72.4% at the time of mastectomy, 23.8% breast conservation surgery, 3.8% axillary surgery alone). Performance of axillary surgery reflected increasing tumour size, micro-invasion or increasing nuclear grade for the final diagnosis of DCIS. More extensive nodal surgery was performed in those undergoing mastectomy; 10.8% of women had more than 8 nodes removed. Overall, 12.0% of women with invasive cancer, 1.7% with micro-invasion, and 0.2% with DCIS alone, were ultimately node positive. Improved pre-operative sampling of DCIS, axillary assessment by ultrasound with needle biopsy for suspected metastases, risk stratification for sentinel node biopsy (for high grade or extensive DCIS) and avoiding axillary clearance for a pre-operative diagnosis of DCIS alone should reduce unnecessary axillary surgery. Standards using such criteria for axillary surgery in screen-detected DCIS should be integrated into the NHS BSP.

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.

Introduction Meta-analysis of published literature suggests that up to 14% of upper gastrointestinal cancer (UGIC) subjects had a negative oesophagogastroduodenoscopy (OGD) up to 3 years prior to diagnosis. We have examined how often UGIC is missed at OGD in our organisation and associated risk factors. Methods Computerised OGD records from Sandwell General and City Hospitals between 1999 and 2007 were retrieved and submitted to the West Midlands Cancer Intelligence Unit (WMCIU) for UGIC registrations linkage. Subjects undergoing OGD 3 months to 5 years before diagnosis were identified as potentially missed UGIC cases and those with no OGD 3 months to 5 years before diagnosis served as controls. The influence of age, gender, indication, endoscopist specialty, trainee involvement, sedation use, number of biopsies taken, site and histology of UGIC on missed UGIC were examined by logistic regression analysis. Results 36577 OGD records were submitted to WMCIU for cancer linkage and 524 UGIC were linked. 419 control UGIC: 388 (93%) diagnosed at initial OGD; 31 (7%) diagnosed at repeat OGD appropriately (within 90 days, with previous benign histology). 105 (20%) potentially missed UGIC cases: 39 (37%) oesophageal cancer (OC) and 66 (63%) gastric cancer (GC); 42 (40%) had OGD 3 months to 1 year prior to diagnosis; 33 (31%) had OGD 1–3 years prior and 30 (29%) had OGD 3–5 years prior. Furthermore, 30% of missed UGIC cases had OGD where abnormality at site of UGIC was seen but not biopsied or benign histology from an inadequate number of biopsies ( < 4) within 3 months to 1 year prior to diagnosis. Lack of alarm symptoms (2.51, 95%CI 1.58–4.00, p = 0.0001) and female gender (1.79, 1.16–2.79, p = 0.009) were associated with missed UGIC. The number of biopsies taken was significantly lower in the missed UGIC group than in the controls (2.1 ± 0.2 vs 5.4 ± 0.1, p < 0.05). In subjects with OC, mid-oesophageal OC appeared more likely to be missed than lower-oesophageal OC (2.04, 0.99–4.23, p = 0.05). Oesophageal squamous cell carcinoma was much more likely to be missed than oesophageal adenocarcinoma (4.47, 1.88–10.65, p < 0.001). In GC subjects, there was no association between missed UGIC and tumour site (1.10, 0.61–1.97, p = 0.3) or histology subtype (1.10, 0.46–2.67, p = 0.8). Age (1.5, –0.8–3.8, p = 0.2), endoscopist specialty (1.39, 0.70–2.76, p = 0.34), trainee involvement (1.2, 0.78 – 1.86, p = 0.39) and sedation use (0.98, 0.64–1.51, p = 0.9) were not associated with increased risk of missing UGIC. Conclusion Missing UGIC at OGD was seen in 14.3% of subjects within 3 years of diagnosis. It was associated with lack of alarm symptoms, female gender, oesophageal squamous cell carcinoma and an insufficient number of biopsies from recognised abnormalities. Disclosure of Interest None Declared

Background: Following primary breast cancer treatment, the early detection of ipsilateral breast tumour recurrence (IBTR) or ipsilateral secondary cancer in the treated breast and detection of new primary cancers in the contralateral breast is beneficial for survival. Surveillance mammography is used to detect these cancers, but the optimal frequency of surveillance and the length of follow-up are unclear. Objectives: To identify feasible management strategies for surveillance and follow-up of women after treatment for primary breast cancer in a UK setting, and to determine the effectiveness and cost-effectiveness of differing regimens. Methods: A survey of UK breast surgeons and radiologists to identify current surveillance mammography regimens and inform feasible alternatives; two discrete systematic reviews of evidence published from 1990 to mid 2009 to determine (i) the clinical effectiveness and cost-effectiveness of differing surveillance mammography regimens for patient health outcomes and (ii) the test performance of surveillance mammography in the detection of IBTR and metachronous contralateral breast cancer (MCBC); statistical analysis of individual patient data (West Midlands Cancer Intelligence Unit Breast Cancer Registry and Edinburgh data sets); and economic modelling using the systematic reviews results, existing data sets, and focused searches for specific data analysis to determine the effectiveness and cost–utility of differing surveillance regimens. Results: The majority of survey respondents initiate surveillance mammography 12 months after breast-conserving surgery (BCS) (87%) or mastectomy (79%). Annual surveillance mammography was most commonly reported for women after BCS or after mastectomy (72% and 53%, respectively). Most (74%) discharge women from surveillance mammography, most frequently 10 years after surgery. The majority (82%) discharge from clinical follow-up, most frequently at 5 years. Combining initiation, frequency and duration of surveillance mammography resulted in 54 differing surveillance regimens for women after BCS and 56 for women following mastectomy. The eight studies included in the clinical effectiveness systematic review suggest surveillance mammography offers a survival benefit compared with a surveillance regimen that does not include surveillance mammography. Nine studies were included in the test performance systematic review. For routine IBTR detection, surveillance mammography sensitivity ranged from 64% to 67% and specificity ranged from 85% to 97%. For magnetic resonance imaging (MRI), sensitivity ranged from 86% to 100% and specificity was 93%. For non-routine IBTR detection, sensitivity and specificity for surveillance mammography ranged from 50% to 83% and from 57% to 75%, respectively, and for MRI from 93% to 100% and from 88% to 96%, respectively. For routine MCBC detection, one study reported sensitivity of 67% and specificity of 50% for both surveillance mammography and MRI, although this was a highly select population. Data set analysis showed that IBTR has an adverse effect on survival. Furthermore, women experiencing a second tumour measuring > 20 mm in diameter were at a significantly greater risk of death than those with no recurrence or those whose tumour was < 10 mm in diameter. In the base-case analysis, the strategy with the highest net benefit, and most likely to be considered cost-effective, was surveillance mammography alone, provided every 12 months at a societal willingness to pay for a quality-adjusted life-year of either £20,000 or £30,000. The incremental cost-effectiveness ratio for surveillance mammography alone every 12 months compared with no surveillance was £4727. Limitations: Few studies met the review inclusion criteria and none of the studies was a randomised controlled trial. The limited and variable nature of the data available precluded any quantitative analysis. There was no useable evidence contained in the Breast Cancer Registry database to assess the effectiveness of surveillance mammography directly. The results of the economic model should be considered exploratory and interpreted with caution given the paucity of data available to inform the economic model. Conclusions: Surveillance is likely to improve survival and patients should gain maximum benefit through optimal use of resources, with those women with a greater likelihood of developing IBTR or MCBC being offered more comprehensive and more frequent surveillance. Further evidence is required to make a robust and informed judgement on the effectiveness of surveillance mammography and follow-up. The utility of national data sets could be improved and there is a need for high-quality, direct head-to-head studies comparing the diagnostic accuracy of tests used in the surveillance population. Funding: The National Institute for Health Research Health Technology Assessment programme.