Pathological features of 11,337 patients with primary ductal carcinoma in situ (DCIS) and subsequent events: results from the UK Sloane Project.

BACKGROUND: The Sloane audit compares screen-detected ductal carcinoma in situ (DCIS) pathology with subsequent management and outcomes. METHODS: This was a national, prospective cohort study of DCIS diagnosed during 2003-2012. RESULTS: Among 11,337 patients, 7204 (64%) had high-grade DCIS. Over time, the proportion of high-grade disease increased (from 60 to 65%), low-grade DCIS decreased (from 10 to 6%) and mean size increased (from 21.4 to 24.1 mm). Mastectomy was more common for high-grade (36%) than for low-grade DCIS (15%). Few (6%) patients treated with breast-conserving surgery (BCS) had a surgical margin <1 mm. Of the 9191 women diagnosed in England (median follow-up 9.4 years), 7% developed DCIS or invasive malignancy in the ipsilateral and 5% in the contralateral breast. The commonest ipsilateral event was invasive carcinoma (n = 413), median time 62 months, followed by DCIS (n = 225), at median 37 months. Radiotherapy (RT) was most protective against recurrence for high-grade DCIS (3.2% for high-grade DCIS with RT compared to 6.9% without, compared with 2.3 and 3.0%, respectively, for low/intermediate-grade DCIS). Ipsilateral DCIS events lessened after 5 years, while the risk of ipsilateral invasive cancer remained consistent to beyond 10 years. CONCLUSION: DCIS pathology informs patient management and highlights the need for prolonged follow-up of screen-detected DCIS.

Optimum screening mammography reading volumes: evidence from the NHS Breast Screening Programme.

OBJECTIVES: Minimum caseload standards for professionals examining breast screening mammograms vary from 480 (US) to 5000 (Europe). We measured the relationship between the number of women's mammograms examined per year and reader performance. METHODS: We extracted routine records from the English NHS Breast Screening Programme for readers examining between 1000 and 45,000 mammograms between April 2014 and March 2017. We measured the relationship between the volume of cases read and screening performance (cancer detection rate, recall rate, positive predictive value of recall (PPV) and discrepant cancers) using linear logistic regression. We also examined the effect of reader occupational group on performance. RESULTS: In total, 759 eligible mammography readers (445 consultant radiologists, 235 radiography advanced practitioners, 79 consultant radiographers) examined 6.1 million women's mammograms during the study period. PPV increased from 12.9 to 14.4 to 17.0% for readers examining 2000, 5000 and 10000 cases per year respectively. This was driven by decreases in recall rates from 5.8 to 5.3 to 4.5 with increasing volume read, and no change in cancer detection rate (from 7.6 to 7.6 to 7.7). There was no difference in cancer detection rate with reader occupational group. Consultant radiographers had higher recall rate and lower PPV compared to radiologists (OR 1.105, p = 0.012; OR 0.874, p = 0.002, unadjusted). CONCLUSION: Positive predictive value of screening increases with the total volume of cases examined per reader, through decreases in numbers of cases recalled with no concurrent change in numbers of cancers detected. KEY POINTS: • In the English Breast Screening Programme, readers who examined a larger number of cases per year had a higher positive predictive value, because they recalled fewer women for further tests but detected the same number of cancers. • Reader type did not affect cancer detection rate, but consultant radiographers had a higher recall rate and lower positive predictive value than consultant radiologists, although this was not adjusted for length of experience.

The Effect of Country of Birth on the Pattern of Disease and Survival From Cervical Cancer.

OBJECTIVE: The aim of the study was to investigate the impact of country of birth on the pattern of disease and survival from cervical cancer in women living in the United Kingdom. MATERIALS AND METHODS: A retrospective database evaluation study was performed to review all cases of cervical cancer diagnosed in the Pan-Birmingham Cancer Network between 2005 and 2009. Population characteristics and survival data were obtained from the West Midlands Cancer Registry and National Health Authority Information System, United Kingdom. Women's country of birth was classified as being high- (including patients born in the United Kingdom and Ireland), middle-, or low-income countries according to the World Bank country classification. Screening histories data were obtained from the West Midlands Cancer Screening Quality Assurance Reference Centre. Overall survival data were analyzed using the nonparametric Kaplan-Meier method with log-rank tests to compare between groups. RESULTS: Four hundred eighty-four cases were identified. A country of birth was available for 459 cases (94.8%). Cancers detected through screening or interval cancers accounted for 140 (28.9%) of cases compared with 226 (46.7%) where women had not complied with screening. Of the women born outside of the United Kingdom/Ireland, 40 (59.7%) originated from low-income, 23 (34.3%) from middle-income, and 4 (6.0%) from high-income countries. Multivariate analysis identified age (p < .001) and stage (p < .001) at diagnosis as having a significant effect on survival, but no effect was seen from social deprivation (p = .18) or economic status of country of birth (p = .30). DISCUSSION: Country of birth is not an independent prognostic indicator for cervical cancer survival.

Development and quality appraisal of a new English breast screening linked data set as part of the age, test threshold, and frequency of mammography screening (ATHENA-M) study.

OBJECTIVES: To build a data set capturing the whole breast cancer screening journey from individual breast cancer screening records to outcomes and assess data quality. METHODS: Routine screening records (invitation, attendance, test results) from all 79 English NHS breast screening centres between January 1, 1988 and March 31, 2018 were linked to cancer registry (cancer characteristics and treatment) and national mortality data. Data quality was assessed using comparability, validity, timeliness, and completeness. RESULTS: Screening records were extracted from 76/79 English breast screening centres, 3/79 were not possible due to software issues. Data linkage was successful from 1997 after introduction of a universal identifier for women (NHS number). Prior to 1997 outcome data are incomplete due to linkage issues, reducing validity. Between January 1, 1997 and March 31, 2018, a total of 11 262 730 women were offered screening of whom 9 371 973 attended at least one appointment, with 139 million person-years of follow-up (a median of 12.4 person years for each woman included) with 73 810 breast cancer deaths and 1 111 139 any-cause deaths. Comparability to reference data sets and internal validity were demonstrated. Data completeness was high for core screening variables (>99%) and main cancer outcomes (>95%). CONCLUSIONS: The ATHENA-M project has created a large high-quality and representative data set of individual women's screening trajectories and outcomes in England from 1997 to 2018, data before 1997 are lower quality. ADVANCES IN KNOWLEDGE: This is the most complete data set of English breast screening records and outcomes constructed to date, which can be used to evaluate and optimize screening.

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.

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.

Invasive breast cancer and breast cancer mortality after ductal carcinoma in situ in women attending for breast screening in England, 1988-2014: population based observational cohort study.

OBJECTIVE: To evaluate the long term risks of invasive breast cancer and death from breast cancer after ductal carcinoma in situ (DCIS) diagnosed through breast screening. DESIGN: Population based observational cohort study. SETTING: Data from the NHS Breast Screening Programme and the National Cancer Registration and Analysis Service. PARTICIPANTS: All 35 024 women in England diagnosed as having DCIS by the NHS Breast Screening Programme from its start in 1988 until March 2014. MAIN OUTCOME MEASURES: Incident invasive breast cancer and death from breast cancer. RESULTS: By December 2014, 13 606 women had been followed for up to five years, 10 998 for five to nine years, 6861 for 10-14 years, 2620 for 15-19 years, and 939 for at least 20 years. Among these women, 2076 developed invasive breast cancer, corresponding to an incidence rate of 8.82 (95% confidence interval 8.45 to 9.21) per 1000 women per year and more than double that expected from national cancer incidence rates (ratio of observed rate to expected rate 2.52, 95% confidence interval 2.41 to 2.63). The increase started in the second year after diagnosis of DCIS and continued until the end of follow-up. In the same group of women, 310 died from breast cancer, corresponding to a death rate of 1.26 (1.13 to 1.41) per 1000 women per year and 70% higher than that expected from national breast cancer mortality rates (observed:expected ratio 1.70, 1.52 to 1.90). During the first five years after diagnosis of DCIS, the breast cancer death rate was similar to that expected from national mortality rates (observed:expected ratio 0.87, 0.69 to 1.10), but it then increased, with values of 1.98 (1.65 to 2.37), 2.99 (2.41 to 3.70), and 2.77 (2.01 to 3.80) in years five to nine, 10-14, and 15 or more after DCIS diagnosis. Among 29 044 women with unilateral DCIS undergoing surgery, those who had more intensive treatment (mastectomy, radiotherapy for women who had breast conserving surgery, and endocrine treatment in oestrogen receptor positive disease) and those with larger final surgical margins had lower rates of invasive breast cancer. CONCLUSIONS: To date, women with DCIS detected by screening have, on average, experienced higher long term risks of invasive breast cancer and death from breast cancer than women in the general population during a period of at least two decades after their diagnosis. More intensive treatment and larger final surgical margins were associated with lower risks of invasive breast cancer.

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.

Risk of subsequent invasive breast cancer after a diagnosis of ductal carcinoma in situ (DCIS).

Despite surgical removal of ductal carcinoma in situ (DCIS), recurrences still occur. This retrospective cohort study evaluated the risk of invasive recurrence following surgery and investigated factors which may be predictive of recurrence. We specifically investigated invasive recurrence with respect to mode of detection of DCIS. Patients whose DCIS was detected outside of the NHS Breast Screening Programme have a higher risk of subsequent ipsilateral invasive breast cancer than those whose DCIS is detected through screening. There is no significant difference in risk of subsequent contralateral invasive recurrence according to mode of detection.