Screen-detected Ductal Carcinoma In Situ Research Articles

Abstract PO4-17-05: Patterns of care: radiotherapy after breast conserving surgery and the use of endocrine therapy for screen-detected ductal carcinoma in situ (DCIS) in the UK

Abstract Background The use of adjuvant radiotherapy (RT) and endocrine therapy (ET) in the management of pure ductal carcinoma in situ (DCIS) remains controversial. We investigate how the use of adjuvant RT after breast conserving surgery (BCS) and use of adjuvant ET (in BCS and mastectomy patients) has changed over time. Methods A prospective cohort SQL database of 11,284 patients (the Sloane Project) diagnosed 2003-2012 with screen-detected DCIS in the UK was interrogated for use of adjuvant RT and ET over time and association with factors reported to be predictive of recurrence (patient age, DCIS nuclear grade, size, comedo necrosis, resection margins), as well as institution of surgery, travel time to radiotherapy facility, Index of Multiple Deprivation and outcome (provided by the National Disease Registration Service, NDRS). RT data by site were confirmed with more recent data from the National Audit of Breast Cancer in Older Patients (NABCOP), which looked at patterns of care and outcomes for women aged 70 years and over, compared with those aged 50-64 in England and Wales. Results Among the 7,949 women (70.6%) treated by BCS, post-operative adjuvant RT was given to 4,939 (62.1%); RT use after BCS increased over time (R2 =0.92; p< 0.01). RT use was associated with year of diagnosis (p < 0.01), younger age at diagnosis (p < 0.01), larger DCIS size (p < 0.01), presence of comedo necrosis (p < 0.01), higher nuclear grade (p < 0.01) and presence of microinvasion (p < 0.01). Adjusted analyses showed the most significant factor for RT after BCS was the surgery institution. Travel time to RT facility, Index of Multiple Deprivation and final radial margin were not associated with RT use. When compared with the more recent data from the NABCOP, a marked variation in radiotherapy use across hospitals remains. Ipsilateral recurrence rate varied significantly by hospital, with some of the difference associated with RT utilisation. ET was prescribed in 1313 women (12%), more often following BCS than mastectomy (p < 0.001), with significant variation by institution and a decline in the use of ET over time. Conclusion Marked geographic variation in the use of RT and ET after surgery for DCIS persists in the UK and is likely due to physician choice rather than other factors such as travel times to RT facilities. This is contributing to geographic variation in ipsilateral recurrence rates, suggesting the need for adoption of more authoritative guidelines to support clinical decision-making. Consistent national practice could provide auditable performance standards for adjuvant therapy of screen detected DCIS and contribute to more uniform patient care. Citation Format: Karen Clements, David Dodwell, Elinor Sawyer, Ramsey Cutress, Nisha Sharma, Abeer Shaaban, Alastair Thompson. Patterns of care: radiotherapy after breast conserving surgery and the use of endocrine therapy for screen-detected ductal carcinoma in situ (DCIS) in the UK [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-17-05.

The long-term psychosocial consequences of screen-detected ductal carcinoma in situ and invasive breast cancer.

Ductal carcinoma in situ (DCIS) is a risk factor for invasive breast cancer (IBC). The prognosis of DCIS is considerably better than for IBC, yet women do not distinguish between the threat. We aimed to compare the psychosocial consequences of screen-detected DCIS and IBC, and to examine this comparison over time. We surveyed a Danish mammography-screening cohort from 2004 to 2018. We assessed outcomes at six-time points: baseline, 1, 6, 18, 36 months, and 14 years after the screening. We measured psychosocial consequences with the Consequences Of Screening - Breast Cancer (COS-BC): a condition-specific questionnaire that is psychometrically validated and encompasses 14 psychosocial dimensions. We used weighted linear models with generalized estimating equations to compare responses between groups. We used a 1% level of significance. 170 out of 1309 women were diagnosed with breast cancer (13.0%). 23 were diagnosed with DCIS (13.5%) and 147 with IBC (86.5%). From baseline to six months after diagnosis, there were no significant differences between women with DCIS and IBC. However, mean scores indicated that IBC generally was more affected than DCIS. After six months, we observed that women with DCIS and IBC might be affected differently in the long term; mean scores and mean differences showed that IBC were more affected on some scales, while DCIS were on others. Overall, the DCIS and IBC experienced similar levels of psychosocial consequences. Women might benefit from renaming DCIS to exclude cancer nomenclature.

Ductal Carcinoma In Situ (DCIS) and Microinvasive DCIS: Role of Surgery in Early Diagnosis of Breast Cancer.

Advances in treatments, screening, and awareness have led to continually decreasing breast cancer-related mortality rates in the past decades. This achievement is coupled with early breast cancer diagnosis. Ductal carcinoma in situ (DCIS) and microinvasive breast cancer have increasingly been diagnosed in the context of mammographic screening. Clinical management of DCIS is heterogenous, and the clinical significance of microinvasion in DCIS remains elusive, although microinvasive DCIS (DCIS-Mi) is distinct from "pure" DCIS. Upfront surgery has a fundamental role in the overall treatment of these breast diseases. The growing number of screen-detected DCIS diagnoses with clinicopathological features of low risk for local recurrence (LR) allows more conservative surgical options, followed by personalised adjuvant radiotherapy plans. Furthermore, studies are underway to evaluate the validity of surgery omission in selected low-risk categories. Nevertheless, the management, the priority of axillary surgical staging, and the prognosis of DCIS-Mi remain the subject of debate, demonstrating how the paucity of data still necessitates adequate studies to provide conclusive guidelines. The current scientific scenario for DCIS and DCIS-Mi surgical approach consists of highly controversial and diversified sources, which this narrative review will delineate and clarify.

Cumulative 6-Year Risk of Screen-Detected Ductal Carcinoma In Situ by Screening Frequency

Detection of ductal carcinoma in situ (DCIS) by mammography screening is a controversial outcome with potential benefits and harms. The association of mammography screening interval and woman's risk factors with the likelihood of DCIS detection after multiple screening rounds is poorly understood. To develop a 6-year risk prediction model for screen-detected DCIS according to mammography screening interval and women's risk factors. This Breast Cancer Surveillance Consortium cohort study assessed women aged 40 to 74 years undergoing mammography screening (digital mammography or digital breast tomosynthesis) from January 1, 2005, to December 31, 2020, at breast imaging facilities within 6 geographically diverse registries of the consortium. Data were analyzed between February and June 2022. Screening interval (annual, biennial, or triennial), age, menopausal status, race and ethnicity, family history of breast cancer, benign breast biopsy history, breast density, body mass index, age at first birth, and false-positive mammography history. Screen-detected DCIS defined as a DCIS diagnosis within 12 months after a positive screening mammography result, with no concurrent invasive disease. A total of 916 931 women (median [IQR] age at baseline, 54 [46-62] years; 12% Asian, 9% Black, 5% Hispanic/Latina, 69% White, 2% other or multiple races, and 4% missing) met the eligibility criteria, with 3757 screen-detected DCIS diagnoses. Screening round-specific risk estimates from multivariable logistic regression were well calibrated (expected-observed ratio, 1.00; 95% CI, 0.97-1.03) with a cross-validated area under the receiver operating characteristic curve of 0.639 (95% CI, 0.630-0.648). Cumulative 6-year risk of screen-detected DCIS estimated from screening round-specific risk estimates, accounting for competing risks of death and invasive cancer, varied widely by all included risk factors. Cumulative 6-year screen-detected DCIS risk increased with age and shorter screening interval. Among women aged 40 to 49 years, the mean 6-year screen-detected DCIS risk was 0.30% (IQR, 0.21%-0.37%) for annual screening, 0.21% (IQR, 0.14%-0.26%) for biennial screening, and 0.17% (IQR, 0.12%-0.22%) for triennial screening. Among women aged 70 to 74 years, the mean cumulative risks were 0.58% (IQR, 0.41%-0.69%) after 6 annual screens, 0.40% (IQR, 0.28%-0.48%) for 3 biennial screens, and 0.33% (IQR, 0.23%-0.39%) after 2 triennial screens. In this cohort study, 6-year screen-detected DCIS risk was higher with annual screening compared with biennial or triennial screening intervals. Estimates from the prediction model, along with risk estimates of other screening benefits and harms, could help inform policy makers' discussions of screening strategies.

Cohort profile of the Sloane Project: methodology for a prospective UK cohort study of >15 000 women with screen-detected non-invasive breast neoplasia

PurposeThe introduction of breast screening in the UK led to an increase in the detection of non-invasive breast neoplasia, predominantly ductal carcinoma in situ (DCIS), a non-obligatory precursor of invasive...

Screen-detected ductal carcinoma in situ, 2008-2020: An observational study.

The purpose of this study was to evaluate the grade distribution of screen-detected ductal carcinoma in situ (DCIS) diagnosed in Ireland, in the context of the clinical trials currently underway to determine if active surveillance is a feasible management option for low-risk DCIS. BreastCheck is the national breast screening programme in Ireland, offering screening to women aged 50 to 69 every two years. This study was a secondary analysis of data collected by BreastCheck on all screen-detected DCIS diagnosed in the 12 years of nationwide screening. Incidence and detection rates were calculated. Descriptive analysis of the cases was performed and, for comparative analysis, grade of DCIS was analysed as a binary variable (high vs. low/intermediate) in keeping with the inclusion criteria for active surveillance trials. Analysis was performed in IBM Statistical Package for Social Sciences, version 26. Between 2008 and 2020, 2240 women were diagnosed with DCIS through BreastCheck; 876 (39.1%) were low/intermediate-grade. The overall incidence rate has remained relatively stable during this period. Women with low/intermediate-grade DCIS were younger than women with high-grade DCIS (56 (interquartile range: 56-61) years v 57 (interquartile range: 53-61) years; p < 0.001). They were also more likely to have been diagnosed at an initial screening episode compared with those who had high-grade lesions (42.5% v 29.0%; p < 0.001). If current clinical trials recommend active surveillance as a feasible option for DCIS, up to 40% of women with screen-detected DCIS may be eligible. These women are younger and often diagnosed on initial screening episode, so may require longer active follow-up.

Abstract P3-12-36: The diagnosis and prognosis of ductal carcinoma in situ (DCIS) with microinvasion - Results from the United Kingdom Sloane project

Abstract Background/objectives The natural history of microinvasive carcinoma of the breast (one or more foci of invasion of 1mm or less) and its optimal management remain controversial. We analysed the frequency and outcome of patients with DCIS plus microinvasion within a large prospective cohort of screen-detected DCIS. Methods Patients with screen-detected DCIS diagnosed between 2003 and 2012 with or without microinvasion in the final surgical specimen were identified from the UK Sloane Project database. Comprehensive imaging, surgical, pathology, oncology and subsequent outcome data were collected with a median follow-up of 9 years. Results Among 11285 DCIS patients diagnosed in the UK, microinvasion was reported in 521 (4.6%). The frequency of reported microinvasion varied considerably among screening units (0-25%) but overall decreased from 7% in 2003/04 to 3% in 2011/12.As reported elsewhere, microinvasion was significantly associated with high grade DCIS (5.9% of 7182 cases) compared to 2.9% of intermediate grade and &amp;lt;1% of low grade DCIS (p&amp;lt;0.001, Chi square test). Microinvasion was associated with larger DCIS size (p&amp;lt;0.001) 2.2% of DCIS &amp;lt;10mm, 3.9% of DCIS 10-20mm, 5.8% of DCIS 20-30mm, 5.2% of DCIS 30-40mm and 8.0% of DCIS &amp;gt;40mm had microinvasive foci reported. Microinvasion was also associated with the presence of comedo necrosis (p&amp;lt;0.001), and solid (p&amp;lt;0.001), cribriform (p&amp;lt;0.001) or flat (p=0.03) DCIS architecture.Microinvasion was identified more frequently in patients who underwent mastectomy (6.9%) than in those who had breast conserving surgery (BCS) (3.6%; p&amp;lt;0.001). Axillary nodal surgery was more commonly performed for microinvasion (60.4% compared to 30.3%) including for patients undergoing BCS (43.4% vs 8.5% of all patients with BCS; p&amp;lt;0.001). The rate of nodal metastasis was, however, low and not statistically significantly different between those with and without microinvasion (0.4% and 0.1% respectively, p=0.27).Patients with microinvasion who underwent BCS were also more likely to receive radiotherapy (p&amp;lt;0.001). There was no significant association between the presence or absence of microinvasion with margin status or width. Subsequent events data for England showed that microinvasion was associated with a low rate of ipsilateral subsequent events, with 2.3% of patients having recurrent DCIS and 4.2% developing invasive carcinoma. This was not statistically significantly different from DCIS without microinvasion. All subsequent ipsilateral DCIS events in patients with microinvasion were of high grade. The majority (71.4%) of subsequent ipsilateral invasive carcinomas were of grade 3 compared with only 30.4% of grade 3 carcinomas in patients with DCIS without microinvasion (p=0.02). Breast cancer mortality was significantly higher in women whose tumours showed microinvasion (2.1%) compared with those without it (0.8%; p=0.005). Conclusions Microinvasion was most commonly identified within high-grade DCIS and in larger DCIS lesions, and was associated with comedo necrosis. Its pathological reporting decreased over a 10-year period, but there was significant variation between departments, which requires further evaluation. Patients with DCIS plus microinvasion were more likely to have undergone mastectomy, axillary node surgery and to receive radiotherapy after BCS. Microinvasive breast carcinoma was associated with a low rate of subsequent in situ/invasive events and had a good prognosis but, nevertheless, a higher breast cancer mortality than DCIS without microinvasion. Citation Format: Abeer M Shaaban, Bridget Hilton, Karen Clements, David Dodwell, Nisha Sharma, Cliona Kirwan, Elinor Sawyer, Anthony Maxwell, Matthew Wallis, Hilary Stobart, Senthurun Mylvaganam, Janet.Litherland Litherland, Samantha Brace-Mcdonnell, Joanne Dulson-Cox, Olive Kearins, Elena Provenzano, Sarah Pinder, Alastair Thompson. The diagnosis and prognosis of ductal carcinoma in situ (DCIS) with microinvasion - Results from the United Kingdom Sloane project [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-36.

Abstract P1-22-06: A longitudinal cohort study of outcomes in 311 women with unresected ductal carcinoma in situ detected through the English breast screening programme

Abstract Background The variable natural history of ductal carcinoma in situ (DCIS) is poorly understood. The aim of this retrospective cohort study was to determine the outcomes of women who were diagnosed through the English National Health Service Breast Screening Programme (NHS BSP) and had no surgery for screen-detected DCIS. Method English NHS BSP databases were searched for women diagnosed with DCIS without invasive cancer on needle biopsy between 1 April 2001 and 31 March 2018 inclusive, who had no record of surgery within 6 months of diagnosis. These were cross-referenced with cancer registry data for further treatment, event information and mortality records. Details of potentially eligible women were sent to the relevant breast screening units for verification and for completion of data forms detailing clinical, radiological and pathological findings, non-surgical treatment, subsequent clinical course and outcomes. Results Data for 311 eligible women (median age 62 years) were included, with median follow-up (primary DCIS diagnosis to either surgery, development of invasive disease, death or last known to be alive) of 4.1 years (range 0.5 to 17.4 years). The median age at diagnosis was 64 years (range 47 to 90 years). Sixty (19%) women developed invasive breast cancer, 56 ipsilateral and 4 contralateral. Twenty-two women (7%) underwent surgery for DCIS (&amp;gt;6 months after diagnosis) and 86 (28%) died of other causes. Women with high or intermediate grade DCIS were significantly more likely to develop ipsilateral invasive breast cancer (iIBC) than those with low grade DCIS. 28/123 (23%) with high grade DCIS, 21/105 (20%) with intermediate grade DCIS, 5/76 (7%) with low grade DCIS and 2/7 (29%) with an unknown grade of DCIS developed iIBC. Ipsilateral invasion risk increased approximately linearly with time for at least 10 years. Women who developed iIBC were significantly younger than those who did not. This was driven primarily by a strong association among those with high grade DCIS. There was no significant difference in age between those with intermediate and low grade DCIS respectively who did or did not develop iIBC. The median baseline size of DCIS in women who developed iIBC was higher than in women who did not develop iIBC, both overall and in each of the three grade categories (median sizes - high grade 38 mm vs 29 mm, p=0.19; intermediate grade 35 mm vs 18 mm, p=0.31; low grade 18 mm vs 15 mm, p=0.38). This reached statistical significance for all grades combined: 37 mm (range 3-95) v 20 mm (range 3-200), p=0.02. Of the 262 women with a known microinvasion status, 8/25 (32%) with definite or possible microinvasion were subsequently diagnosed with ipsilateral invasive cancer compared to 38/237 (16%) without microinvasion (p=0.027). There was no significant association on univariable analysis between risk of iIBC and microcalcification as the predominant radiological feature (iIBC and microcalcification 47/258 vs iIBC and other radiological feature 7/46; p=0.83), the presence of histological necrosis (iIBC and necrosis, 14/89 vs iIBC and no necrosis, 31/157; p=0.49) or the use of ET (iIBC and ET 11/67 vs iIBC and no ET 45/244; p=0.86). Of the 51 invasive cancers that developed with a known grade, 46 (90%) were grade 2 or 3. Conclusion The findings suggest that women diagnosed with high or intermediate grade DCIS and those with microinvasion should continue to be offered surgery. For those with low grade DCIS there is a need for shared decision-making in the choice of surgery or active surveillance based on a discussion of the risks and benefits of the options as currently understood, and in the light of the low reproducibility of DCIS grading. Citation Format: Karen Clements, Anthony Maxwell, Bridget Hilton, Matthew Wallis, Cliona Kirwan, Hilary Stobart, Elena Provenzano, Nisha Sharma, Janet Litherland, Abeer Shaaban, David Dodwell, Joanne Dulson-Cox, Elinor Sawyer, Senthurun Mylvaganam, Olive Kearins, Samantha Brace-McDonnell, Sarah Pinder, Alastair Thompson. A longitudinal cohort study of outcomes in 311 women with unresected ductal carcinoma in situ detected through the English breast screening programme [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-22-06.

Unresected screen-detected ductal carcinoma in situ: Outcomes of 311 women in the Forget-Me-Not 2 study

Background and aimThe natural history of ductal carcinoma in situ (DCIS) is poorly understood. The aim of this cohort study was to determine the outcomes of women who had no surgery for screen-detected DCIS in the 6 months following diagnosis. MethodsEnglish breast screening databases were retrospectively searched for women diagnosed with DCIS without invasive cancer at screening and who had no record of surgery within 6 months of diagnosis. These were cross-referenced with cancer registry data. Details of the potentially eligible women were sent to the relevant breast screening units for verification and for completion of data forms detailing clinical, radiological and pathological findings, non-surgical treatment and subsequent clinical course. ResultsData for 311 eligible women (median age 62 years) were available. 60 women developed invasive cancer, 56 ipsilateral and 4 contralateral. Ipsilateral invasion risk increased approximately linearly with time for at least 10 years. The 10-year cumulative risk of ipsilateral invasion was 9% (95% CI 4–21%), 39% (24–58%) and 36% (24–50%) for low, intermediate and high grade DCIS respectively and was higher in younger women, in those with larger DCIS lesions and in those with microinvasion. Most invasive cancers that developed were grade 2 or 3. ConclusionThe findings suggest that active surveillance may be a reasonable alternative to surgery in patients with low grade DCIS but that women with intermediate or high grade disease should continue to be offered surgery. This highlights the importance of reproducible grading of DCIS to ensure patients receive appropriate treatment.

Ductal Carcinoma in Situ in Ireland, 2008-2020: Screening Data related to Low-Risk Management Trials

Abstract Background Four clinical trials are on-going to determine if active surveillance is a feasible management option for patients with low-risk ductal carcinoma in situ (DCIS), in response to concerns that breast cancer screening programmes have increased the incidence of DCIS, some of which may never progress to invasive cancer. This study aimed to describe the epidemiology of screen-detected DCIS in Ireland through the BreastCheck, the national breast screening programme in Ireland (commenced 2000 but fully national since 2008). Methods This was a cross-sectional analysis of anonymised BreastCheck data provided by the National Screening Service, including all cases of screen-detected DCIS between 2008 and 2020. Statistical tests included Mann-Whitney U, Chi square, and multivariable logistic regression. Results 2,240 women were diagnosed with DCIS through BreastCheck between 2008 and 2020 (1353 (60.4%) high-grade and 876 (39.1%) low/intermediate grade). The overall rate of screen-detected DCIS incidence has remained relatively stable during this time. Women with high- grade DCIS were older than women with low/intermediate DCIS (57 (IQR 53-61) years v 56 (IQR 56-61) years; p &amp;lt; 0.001). They were also more likely to have been diagnosed at a subsequent screening episode than at an initial episode (71.0% v 57.5%; p &amp;lt; 0.001). After adjustment (deprivation score, screening unit and year) the odds ratio for high-grade was 1.62 (95% CI 1.30-2.03; p &amp;lt; 0.001) for subsequent compared with initial screening episode. Conclusions When trial results are available, these data will assist with service planning should active surveillance be approved as a management option. Based on trial inclusion criteria, up to 40% of women diagnosed with DCIS through BreastCheck may be eligible for consideration for active surveillance. These women are younger and often diagnosed on initial screening episode, so may require longer active follow-up. Key messages Majority of DCIS in national screening programme is high grade. Randomised controlled trial evidence will provide guidance on management of low-risk DCIS.

Disparities in surveillance imaging after breast conserving surgery for primary DCIS.

6516 Background: Due to the elevated risk of ipsilateral invasive breast cancer (iIBC) after diagnosis with primary ductal carcinoma in situ (DCIS), professional guidelines recommend surveillance screening within 6-12 months (mo) after completion of initial local treatment and annually thereafter. To characterize adherence to these guidelines, we explored longitudinal patterns of utilization and factors associated with the use of surveillance imaging (mammography, MRI, ultrasound) for women with primary DCIS treated with breast conserving surgery (BCS) ± radiotherapy (RT) within 6 mo of diagnosis. Methods: A treatment-stratified random sample of patients diagnosed with screen-detected and biopsy-confirmed DCIS in 2008-15 was selected from 1,330 Commission on Cancer-accredited facilities (up to 20/site) in the US. All imaging exams coded as asymptomatic were collected from 6 mo up to 10 years (yr) post-diagnosis. Time was defined according to 12-mo long surveillance periods. To be included in a given surveillance period, women had to be alive and free of a new breast cancer diagnosis through the end of the period. Women were classified as “consistent” screeners if they had at least one surveillance screen during each period, for the first 5 yr post-treatment or until censoring, whichever occurred first. Repeated measures multivariable logistic regression with generalized estimating equations was used to model receipt of surveillance breast imaging over time. The model included clinical and socioeconomic features. Results: The final analytic cohort contained 12,559 women; 8,989 (71.6%) received RT after BCS. Median age was 60 yr (interquartile range: 52-69) and median follow-up was 5.6 yr (95% confidence interval [CI] 5.6-5.7). Among women who received BCS (instead of BCS+RT), 62.5% (79.7%) underwent surveillance imaging within 6-18 mo after diagnosis. 38.7% (54.0%) were categorized as “consistent” screeners. Compared to white women, Black women were less likely to receive surveillance screening after treatment for primary DCIS (odds ratio [OR] 0.85, 95% CI 0.77-0.94). Hispanic ethnicity had a similar association (OR 0.86, 95% CI 0.74-0.99) compared to non-Hispanic ethnicity. Women with private insurance, compared to government insurance, were more likely to receive screening (OR 1.20, 95% CI 1.11-1.30). Prognostic tumor features indicative of a higher risk of subsequent iIBC, including higher grade, presence of comedonecrosis, and hormone receptor-negative DCIS, were not associated with screening uptake. Conclusions: Despite guidelines recommending annual surveillance imaging, many women with primary DCIS do not undergo regular imaging after BCS. The findings from this US-based study suggest that disparities in screening uptake are associated with race/ethnicity and insurance status rather than prognostic tumor features.

Patterns of aggressiveness: risk of progression to invasive breast cancer by mammographic features of calcifications in screen-detected ductal carcinoma in situ.

Mammographic features of calcifications on mammograms showing invasive breast cancer are associated with survival. Less is known about mammographic features and progression to invasive breast cancer among women treated for ductal carcinoma in situ (DCIS). To investigate mammographic features of calcifications in screen-detected DCIS in women who later did and did not get diagnosed with invasive breast cancer. This registry-based nested case-control study analyzed data from women with screen-detected DCIS in BreastScreen Norway, 1995-2016. Within this cohort of women with DCIS, those who were later diagnosed with invasive breast cancer (cases) were matched (1:2) to women who were not diagnosed with invasive breast cancer (controls) after their DCIS and by the end of 2016. Information on mammographic features were collected by a national radiological review, where screening mammograms were reviewed locally at each of the 16 breast centers in Norway. We used conditional logistic regression analysis to estimate associations between mammographic features of calcifications in the DCIS mammogram and the risk of subsequent invasive breast cancer. We found a higher risk of invasive breast cancer associated with fine linear branching (casting) morphology (odds ratio 20.0; 95% confidence interval [CI] 2.5-158.9) compared to fine linear or fine pleomorphic morphology. Regional or diffuse distribution showed an odds ratio of 2.8 (95% CI 1.0-8.2) compared to segmental or linear distribution. Mammographic features of calcifications in screen-detected DCIS were of influence on the risk of invasive breast cancer. Unfavorable characteristics of DCIS were fine linear branching morphology, and regional or diffuse distribution.

Abstract S02-02: The impact of resuming the breast cancer screening program in the Netherlands on breast cancer incidence and stage after its discontinuation due to the COVID-19 pandemic

Abstract Introduction: The burden of the COVID-19 pandemic forced the Dutch health care services to discontinue their national screening programs on 16 March 2020 (week 12). For breast cancer, the program invites women aged 50–74 years for biennial screening mammography. From mid-June 2020 (week 25) the breast cancer screening program was resumed, albeit with reduced capacity (max 60%). We aimed to investigate the impact of resuming the screening program on incidence, tumor-, and T-stage of screen- and non-screen-detected ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC) in the Netherlands. Methods: Women, 50-74 years of age, diagnosed with DCIS or IBC in weeks 2–35 of 2018, 2019 and 2020 were selected from the Netherlands Cancer Registry. Weekly incidence of screen- and non-screen-detected tumors was calculated and expressed per 1 million women aged 50-74 years living in the Netherlands. Weeks 2-35 were divided in seven periods, representing separate phases of the pandemic. For each period, incidence of screen- and non-screen-detected tumors was stratified by clinical tumor stage (TNM) and clinical T-stage. Incidence in each period of 2020 was compared with the incidence in the same period of 2018/2019 (averaged). Results: In weeks 2-35, 7,250 patients were diagnosed in 2018, 7,299 in 2019, and 5,300 in 2020. During weeks 2-12 2020 the weekly average incidence of screen-detected tumors was 42/1 million women aged 50-74. In week 13 incidence dropped to 19, and was almost zero during weeks 14-25. Incidence increased to 4 in week 26, when the screening was gradually restarted, and increased to an weekly average of 24 tumors/1 million in weeks 30-35, when screening had restarted in most of the Netherlands. During weeks 14-16, 17-25, 26-29, and 30-35 2020 incidence of screen-detected DCIS, stage I-II tumors and T0-2 tumors was lower than in the same period of 2018/2019. Distribution of tumor- and T-stage in newly diagnosed tumors did not differ between the periods (24% DCIS, 57% stage I, 18% stage II, 1% stage III, 1% stage IV; 24% T0, 59% T1, 15% T2, 2% T3, 0% T4). During weeks 2-11 2020 the weekly average incidence of non-screen-detected tumors was 38/1 million women aged 50-74. Incidence dropped to 16 in week 14, and increased to an average of 37 tumors per week in weeks 17-35. During weeks 17-25, 26-29, and 30-35 the incidence and distribution of non-screen-detected DCIS, stage I-IV and T0-4 tumors was comparable with 2018/2019 (weekly incidence (distribution): 3 DCIS (9%), 15 stage I (40%), 13 stage II (36%), 3 stage III (7%), 3 stage IV (8%); 3 T0 (9%), 17 T1 (45%), 12 T2 (34%), 3 T3 (8%), 2 T4 (5%)). Conclusion: The temporary suspension of the breast cancer screening program reduced the incidence of breast cancer. After resuming screening the incidence did not raise above the incidence in 2018/2019, therefore it is expected that the incidence will rise during the next months. The results to date did not show a shift towards a higher tumor stage or T-stage. Citation Format: Anouk H. Eijkelboom, Linda de Munck, Marc B.I. Lobbes, Jelle Wesseling, Carla H. van Gils, Pieter J. Westenend, Cristina Guerrero Paez, Ruud M. Pijnappel, Helena M. Verkooijen, Mireille J.M. Broeders, Sabine Siesling. The impact of resuming the breast cancer screening program in the Netherlands on breast cancer incidence and stage after its discontinuation due to the COVID-19 pandemic [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr S02-02.

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

BackgroundThe Sloane audit compares screen-detected ductal carcinoma in situ (DCIS) pathology with subsequent management and outcomes.MethodsThis was a national, prospective cohort study of DCIS diagnosed during 2003–2012.ResultsAmong 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.ConclusionDCIS pathology informs patient management and highlights the need for prolonged follow-up of screen-detected DCIS.

Contralateral breast cancer risk in patients with ductal carcinoma in situ and invasive breast cancer

We aimed to assess contralateral breast cancer (CBC) risk in patients with ductal carcinoma in situ (DCIS) compared with invasive breast cancer (BC). Women diagnosed with DCIS (N = 28,003) or stage I–III BC (N = 275,836) between 1989 and 2017 were identified from the nationwide Netherlands Cancer Registry. Cumulative incidences were estimated, accounting for competing risks, and hazard ratios (HRs) for metachronous invasive CBC. To evaluate effects of adjuvant systemic therapy and screening, separate analyses were performed for stage I BC without adjuvant systemic therapy and by mode of first BC detection. Multivariable models including clinico-pathological and treatment data were created to assess CBC risk prediction performance in DCIS patients. The 10-year cumulative incidence of invasive CBC was 4.8% for DCIS patients (CBC = 1334). Invasive CBC risk was higher in DCIS patients compared with invasive BC overall (HR = 1.10, 95% confidence interval (CI) = 1.04–1.17), and lower compared with stage I BC without adjuvant systemic therapy (HR = 0.87; 95% CI = 0.82–0.92). In patients diagnosed ≥2011, the HR for invasive CBC was 1.38 (95% CI = 1.35–1.68) after screen-detected DCIS compared with screen-detected invasive BC, and was 2.14 (95% CI = 1.46–3.13) when not screen-detected. The C-index was 0.52 (95% CI = 0.50–0.54) for invasive CBC prediction in DCIS patients. In conclusion, CBC risks are low overall. DCIS patients had a slightly higher risk of invasive CBC compared with invasive BC, likely explained by the risk-reducing effect of (neo)adjuvant systemic therapy among BC patients. For support of clinical decision making more information is needed to differentiate CBC risks among DCIS patients.

Prognostic value of histopathological DCIS features in a large-scale international interrater reliability study

PurposeFor optimal management of ductal carcinoma in situ (DCIS), reproducible histopathological assessment is essential to distinguish low-risk from high-risk DCIS. Therefore, we analyzed interrater reliability of histopathological DCIS features and assessed their associations with subsequent ipsilateral invasive breast cancer (iIBC) risk.MethodsUsing a case-cohort design, reliability was assessed in a population-based, nationwide cohort of 2767 women with screen-detected DCIS diagnosed between 1993 and 2004, treated by breast-conserving surgery with/without radiotherapy (BCS ± RT) using Krippendorff’s alpha (KA) and Gwet’s AC2 (GAC2). Thirty-eight raters scored histopathological DCIS features including grade (2-tiered and 3-tiered), growth pattern, mitotic activity, periductal fibrosis, and lymphocytic infiltrate in 342 women. Using majority opinion-based scores for each feature, their association with subsequent iIBC risk was assessed using Cox regression.ResultsInterrater reliability of grade using various classifications was fair to moderate, and only substantial for grade 1 versus 2 + 3 when using GAC2 (0.78). Reliability for growth pattern (KA 0.44, GAC2 0.78), calcifications (KA 0.49, GAC2 0.70) and necrosis (KA 0.47, GAC2 0.70) was moderate using KA and substantial using GAC2; for (type of) periductal fibrosis and lymphocytic infiltrate fair to moderate estimates were found and for mitotic activity reliability was substantial using GAC2 (0.70). Only in patients treated with BCS-RT, high mitotic activity was associated with a higher iIBC risk in univariable analysis (Hazard Ratio (HR) 2.53, 95% Confidence Interval (95% CI) 1.05–6.11); grade 3 versus 1 + 2 (HR 2.64, 95% CI 1.35–5.14) and a cribriform/solid versus flat epithelial atypia/clinging/(micro)papillary growth pattern (HR 3.70, 95% CI 1.34–10.23) were independently associated with a higher iIBC risk.ConclusionsUsing majority opinion-based scores, DCIS grade, growth pattern, and mitotic activity are associated with iIBC risk in patients treated with BCS-RT, but interrater variability is substantial. Semi-quantitative grading, incorporating and separately evaluating nuclear pleomorphism, growth pattern, and mitotic activity, may improve the reliability and prognostic value of these features.

Interobserver Variability in Ductal Carcinoma In Situ of the Breast.

Since most patients with ductal carcinoma in situ (DCIS) of the breast are treated upon diagnosis, evidence on its natural progression to invasive carcinoma is limited. It is estimated that around half of the screen-detected DCIS lesions would have remained indolent if they had never been detected. Many patients with DCIS are therefore probably overtreated. Four ongoing randomized noninferiority trials explore active surveillance as a treatment option. Eligibility for these trials is mainly based on histopathologic features. Hence, the call for reproducible histopathologic assessment has never sounded louder. Here, the available classification systems for DCIS are discussed in depth. This comprehensive review illustrates that histopathologic evaluation of DCIS is characterized by significant interobserver variability. Future digitalization of pathology, combined with development of deep learning algorithms or so-called artificial intelligence, may be an innovative solution to tackle this problem. However, implementation of digital pathology is not within reach for each laboratory worldwide. An alternative classification system could reduce the disagreement among histopathologists who use "conventional" light microscopy: the introduction of dichotomous histopathologic assessment is likely to increase interobserver concordance. Reproducible histopathologic assessment is a prerequisite for robust risk stratification and adequate clinical decision-making. Two-tier histopathologic assessment might enhance the quality of care.

Ipsilateral invasive cancer risk after diagnosis with ductal carcinoma in situ (DCIS): Comparison of patients with and without index surgery.

519 Background: Most women diagnosed with ductal carcinoma in situ (DCIS) undergo surgical resection, potentially leading to overtreatment of patients who would not develop clinically significant breast cancer in the absence of locoregional treatment. We compared the risk of ipsilateral invasive breast cancer (iIBC) between DCIS patients who received breast conserving surgery (BCS) for their index diagnosis of DCIS (BCS group) and patients who did not receive any locoregional treatment within 6 months of diagnosis (surveillance [SV] group). Methods: A treatment-stratified random sample of patients diagnosed with screen-detected and biopsy-confirmed DCIS in 2008-14 was selected from 1,330 Commission on Cancer-accredited facilities (20/site). Excluding patients who received a mastectomy ≤6 months, the final analytic cohort contained 14,245 (88.2%) BCS and 1,914 (11.8%) SV patients. Subsequent breast events were abstracted up to 10 years after diagnosis. Primary outcome was the 8-year absolute difference in iIBC risk between BCS and SV; a subgroup analysis was performed for grade I/II patients. A propensity score (PS) model for treatment was fitted with sampling design (SD) weighting and random effects for patients within facilities. Absolute risk differences were estimated using PS-SD-weighted Kaplan Meier estimators. Results: Overall, median age at diagnosis was 61 years (IQR: 52-69) and median follow-up was 5.8 years (95% CI 5.7-6.1). The majority of patients were Caucasian (81.9%), with estrogen receptor-positive (80.6%), and nuclear grade I/II (54.5%) DCIS. The fraction of patients with a Charlson comorbidity score of ≥2 was higher in SV (14.2%) compared to BCS (6.4%, p &lt; 0.001). The 8-year risk of iIBC was 3.0% (95% CI: 2.4%-3.6%) for BCS and 7.7% (95% CI: 4.9%-10.5%) for SV, with an absolute risk difference of 4.7% (95% CI: 4.5%-4.9%; log-rank p &lt; 0.001). Among patients with grade I/II tumors, the 8-year risk of iIBC was 3.1% (95% CI: 2.3%-4.0%) for BCS and 6.1% (95% CI: 2.5%-9.8%) for SV; difference: 3.0% (95% CI: 2.7%-3.2%; p = 0.005). Conclusions: Despite an increased risk of iIBC in SV patients compared to BCS patients, the 8-year risk did not exceed 10% in either group. The risk of recurrence in BCS patients was comparable to previously reported estimates. These data demonstrate a considerable degree of overtreatment among patients with non-high grade DCIS. Prospective clinical trials will help determine the tradeoffs between universally directed as opposed to selectively applied surgery for low risk DCIS.

Multimodality Imaging of Ductal Carcinoma In Situ

We aim to review the appearance of ductal carcinoma in situ (DCIS) across the spectrum of imaging modalities used in common clinical practice. Changes in technology and clinical breast cancer screening patterns have impacted the imaging evaluation of DCIS. DCIS classically presents as asymptomatic calcifications in women undergoing screening mammography. The replacement of traditional 2D mammography with digital breast tomosynthesis has changed the typical appearance of screen-detected DCIS. Ultrasound is traditionally utilized to detect DCIS in women with clinical symptoms, but efforts to increase screening ultrasound rates for women with dense breasts makes it more important to identify the appearance of DCIS in asymptomatic women. Improvements in MRI technology have made MRI the most sensitive imaging modality to detect DCIS and define the extent of disease, which is increasingly important given greater utilization of MRI for high-risk screening and determination of extent of known disease. Finally, the emergence of active surveillance, or non-surgical management, for DCIS has increased the focus on presurgical identification of associated invasive cancer, with early results demonstrating promise via computer vision and deep learning approaches for this task. DCIS has a highly variable imaging appearance which is subject to changes in imaging technology and clinical management.

Low-grade screen-detected ductal carcinoma in situ progresses more slowly than high-grade lesions: evidence from an international multi-centre study.

Nuclear grade is an important indicator of the biological behaviour of ductal carcinoma in situ (DCIS). De-escalation of treatment has been suggested for low-grade DCIS. Our aim is to estimate the relative rate of progression of DCIS by nuclear grade by analysing the distribution of nuclear grade by detection at initial or subsequent screening. We asked International Cancer Screening Network sites to complete, based on their screening and clinical databases, an aggregated data file on DCIS detection, diagnosis and treatment. Eleven screening programs reported 5068 screen-detected pure DCIS in nearly 7 million screening tests in women 50-69years of age. For all programs combined, low-grade DCIS were 20.1% (range 11.4-31.8%) of graded DCIS, intermediate grade 31.0% and high grade 48.9%. Detection rates decreased more steeply from initial to subsequent screening in low compared to high-grade DCIS: the ratios of subsequent to initial detection rates were 0.39 for low grade, 0.51 for intermediate grade, and 0.75 for high grade (p < 0.001). These results suggest that the duration of the preclinical detectable phase is longer for low than for high-grade DCIS. The findings from this large multi-centre, international study emphasize that the management of low-grade DCIS should be carefully scrutinized in order to minimize overtreatment of screen-detected slow-growing or indolent lesions. The high variation by site in the proportion of low grade suggests that further pathology standardization and training would be beneficial.