Incidence Of Ductal Carcinoma In Situ Research Articles

Incidence trends of ductal carcinoma in situ in New Zealand women between 1999 and 2022.

In New Zealand, BreastScreen Aotearoa (BSA), a biennial national breast screening programme, was implemented in 1998. This study examines the incidence trends of ductal carcinoma in situ (DCIS) in New Zealand women from 1999 to 2022. All women with a primary diagnosis of DCIS over the 24-year study period were identified from the New Zealand Cancer Registry and BSA records. Age-standardised incidence rates (ASIR), detection rates (ASDR) and average annual percent changes were calculated. The annual ASIR was 13.5 per 100,000 New Zealand women, and increased by 0.91% (95% confidence interval (CI): 0.26%, 1.66%) annually. Among women aged 45-69years during 2006-2022, the annual ASIR was 36.3 for programme-detected DCIS, increasing 1.29% (95%CI: 0.13%, 2.73%) per year, and 14.2 for non-programme-detected DCIS, with no significant changes over the study period. The programme-detected ASIRs were highest for Pacific (38.6), Asian (38.2), and Māori (38.0) women. The programme ASDR was 0.55 per 1000 women screened, with no significant changes over time, and was highest for Asian (0.69), and Māori and Pacific (both at 0.65) women. DCIS incidence increased in New Zealand women from 1999 to 2022, driven by an increase in screening participation, and varied by ethnicity.

Disease recurrence in patients undergoing mastectomy for ductal carcinoma in situ.

With DCIS incidence on the rise, up to 30% of patients undergo mastectomy for Ductal carcinoma in situ (DCIS) (Nash and Hwang, in: Ann Surg Oncol 30(6):3206-3214, 2023). Local recurrence rates after mastectomy for DCIS are reportedly low, but risk factors for recurrence are not known (Kim et al., in: J Cancer Res Ther 16(6):1197-1202, 2020). We aim to define risk factors associated with ipsilateral breast cancer recurrence in patients undergoing mastectomy for DCIS. We aimed to identify risk factors that may contribute to recurrence of breast cancer following mastectomy for pure DCIS. We hypothesized that close or positive mastectomy margins, age at diagnosis, extent of breast disease and mutation carriers would be associated with increased risk of recurrence. We performed a retrospective chart review of patients who underwent unilateral or bilateral mastectomies for pure DCIS at a single academic tertiary referral center from 2013 to 2023. There were 165 patients who met inclusion criteria with an average length of follow-up of 39.9months. On final surgical pathology, the average span of DCIS was 33.7mm (± 24.6mm). Hormone receptor positive disease was identified in 80.6% of the patient cohort. For margin status, 23 patients (14%) had < 1mm margins on final pathology and of those, 1 received adjuvant radiation therapy and 4 returned to the OR for re-excision. Only 1 (0.6%) patient had ipsilateral disease recurrence during the study period. Recurrence after mastectomy for pure DCIS is a rare event and in our study sample, only one recurrence occurred. Risk factors for recurrence appear unrelated to margin status, age, extent of DCIS, or pathogenic mutation (ElSherif et al., in Am J Surg 226(5):646-651, 2023).

Advancements in managing pure ductal carcinoma in situ: An 18-year artificial intelligence-aided analysis of 998 patients

IntroductionThe integration of artificial intelligence (AI) in oncological diseases has opened new avenues for early cancer detection, accurate risk assessments, and personalized treatment protocols. The objective of our study was to describe the shift in the treatment indications and prognosis of ductal carcinoma in situ (DCIS) in a prospective cohort of 998 patients managed over 18 years at a single University Hospital in France. MethodsThis analysis included all patients managed for DCIS at the University Hospitals of Strasbourg between January 14, 2002, and December 18, 2019, from the prospective SENOMETRY cohort, which initially included 9599 patients with both in situ and invasive breast cancer. Data were analyzed using Onconum, an AI-based natural language processing tool, to extract structured information from medical records. ResultsThe incidence of DCIS remained stable at 65 new cases per year. The mean age at diagnosis increased from 55 years in 2002 to 61 years in 2019. There was a significant rise in high-grade DCIS (DIN3) cases from 25% to 35%. The re-excision rate decreased from 57% in 2002 to 18% in 2019. Most DCIS cases were managed with breast-conserving surgeries (682), while total mastectomies accounted for 385 cases. Sentinel lymph node biopsy was performed in 39% of cases, primarily in high-grade and multifocal DCIS. Specific mortality was 0%, with a recurrence rate of 2.2%, predominantly invasive and occurring earlier in high-grade DCIS. Discussion: Over 18 years, there has been a notable shift in the clinicopathological characteristics of DCIS, with an increase in patient age at diagnosis and higher histopathological grades. Therapeutic management evolved significantly, with reduced surgical margins and fewer adjuvant treatments, while maintaining low and stable recurrence rates. AI significantly enhanced data extraction and analysis efficiency, contributing to better clinical decision-making. ConclusionThe study confirms the possibility of therapeutic de-escalation in DCIS, supported by AI-driven data analysis, allowing individualized treatment approaches and leading to optimized patient outcomes.

Abstract PO2-11-02: Incidence, treatment patterns and outcomes of breast cancer during the first year of the COVID pandemic: A population-based study

Abstract Background: The COVID pandemic created significant challenges in breast cancer (BC) care which were most pronounced during 2020 when screening and treatment access were reduced. The aims of this study were to evaluate and compare the incidence of BC, treatment patterns, and outcomes during the year 2020 versus the immediate pre-pandemic (2018 and 2019) period. Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) program, we calculated age-adjusted incidence rates of ductal carcinoma in situ (DCIS) and invasive BC during 2018, 2019 and 2020, with a 95% confidence interval (CI) for each. In the invasive BC cohort, we compared chemotherapy and radiation utilization by year. To account for potential misclassification of cause of death (COD) during the pandemic, we evaluated outcomes by overall survival (OS) in the invasive cohort, defined as time from BC diagnosis until death from any cause. To assess the impact of COVID, OS was truncated at 12 months from diagnosis for each year and we compared OS at 12 months for patients (pts) diagnosed with invasive BC in 2020 versus 2018 and 2019. OS was compared in a multivariable Cox model with diagnosis year 2020 as the reference. The Cox model was adjusted for age at diagnosis, race and ethnicity, sex, tumor grade, histology, stage, tumor subtype, surgery, radiation, chemotherapy, marital status, median household income, and rurality. Results: There were 37,834 DCIS diagnoses, and 199,594 invasive BC diagnoses between 2018-2020, with the distribution by year shown in the table. In 2020, the age-adjusted incidence of female DCIS decreased to 31.0 cases per 100,000, and the age-adjusted incidence of female invasive BC decreased to 166.6 cases per 100,000. As shown in the table, the incidence of male BC did not change. Among females, the relative reductions in incidence from 2019 to 2020 were: 15% for DCIS, 12% for stage I, 6% for stage II, 3% for stage III, and 2% for stage IV. Comparing 2020 to 2018-2019, we observed small absolute decreases in the proportions of pts who had surgery (2%) or radiation therapy (2.8%), and a small absolute increase in chemotherapy (1.4%) (p&amp;lt; 0.001 for each). These treatment changes were present across each individual stage. The table shows the 12-month OS rates for each year of diagnosis. COVID was the COD for 77 pts in 2020, 43 pts in 2019 and 0 pts in 2018. In the Cox model, there were no significant differences in the risk of death between pts diagnosed 2018 and 2020 (adjusted Hazard Ratio: 0.95; 95% CI, 0.90 – 1.01; p=0.13) or between pts diagnosed 2019 and 2020 (adjusted Hazard Ratio: 0.95; 95% CI, 0.89 – 1.01; p=0.08). Conclusions: During the first year of the pandemic, the incidence of BC decreased significantly, largely driven by a decrease in DCIS and early-stage diagnoses. Of interest, there was no stage shift observed with respect to the incidence of stage III or de novo stage IV disease, and no change in male BC incidence. We hypothesize that the observed trends are due to a reduction in screening, but this needs further study. It will be critical to evaluate future trends in cancer incidence beyond 2020, as it is possible that the reduction in early-stage diagnoses represent missed diagnoses that will be identified at a later stage in subsequent years. Finally, while there was no difference in 12-month OS by year of diagnosis, the true impact of the COVID pandemic on BC-specific outcomes will require further follow-up. Citation Format: Jose Leone, Julieta Leone, Michael Hassett, Rachel Freedman, Jorge Avila, Carlos Vallejo, Nabihah Tayob, Sara Tolaney, Nancy Lin. Incidence, treatment patterns and outcomes of breast cancer during the first year of the COVID pandemic: A population-based study [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 PO2-11-02.

Temporal changes in the incidence of ductal carcinoma in situ in Goiânia, Brazil: a population-based study

Introduction: Mammography screening has resulted in a considerable increase in the diagnosis of early-stage tumors in various countries. However, most available data refer to high-income countries, hospital-based studies, or studies with limited follow-up. Therefore the aim of this study was to determine the incidence of ductal carcinoma in situ (DCIS) in Goiânia, Brazil. Methods: Ecological study among residents of the city of Goiânia, Brazil. We included all the DCIS cases registered at the Goiânia population-based cancer registry between 1994 and 2010. Crude incidence and age-standardized incidence rates (using the world standard population) were calculated. Poisson regression was used to analyze temporal changes, with the average annual percent change (AAPC) in the crude and age-standardized incidence rates being calculated. Results: There were 261 cases of DCIS, with an annual incidence rate that ranged from 0.58 to 4.21 per 1,000 women (crude and standardized) over the period. The number of cases of DCIS in the 40–49 and 60–69-years age groups increased significantly (p&lt;0.01). The AAPC of the crude incidence rate for the period was 11.88% per year (95%CI 9–15; p&lt;0.01) and the standardized rate was 11.89% per year (95%CI 9–15; p&lt;0.01). Conclusions: The incidence of DCIS in Goiânia increased between 1994 and 2010, possibly due to improved mammography screening. The present study, which was conducted in a consolidated population-based cancer registry (PBCR) and involved an extensive follow-up time, could contribute towards increasing epidemiological knowledge on DCIS and its variations around the world.

Abstract 2875: Evidence of immunosuppression in patients with breast ductal carcinoma in situ

Abstract Introduction: Ductal carcinoma in situ (DCIS) is a noninvasive precursor to invasive breast cancer. Although not all DCISlesions progress to cancer, most DCIS are treated as early breast cancer, given the uncertainty of which lesions will progress. The current increase in the incidence of DCIS has sparked interest in the immune contexture of the DCIS lesions as well as the immune status of DCIS patients, as a means to predict which DCIS lesions will progress to cancer. Studies done so far in invasive breast cancer showed that the immune system can mediate both tumor-promoting influence (via T regulatory (Treg) cells, M2 macrophages, myeloid-derived suppressor cells (MDSCs)), as well as tumor-suppressing influences (via CD8+ and CD4+ effector T cells, natural killer cells (NK), M1 macrophages, tissue-resident memory T (Trm) cells, B cell and dendritic (DCs) cells). Similar studies are still lacking in DCIS. Our aim was to start closing the gap in our understanding of the DCIS immune microenvironment, which will pave the way for novel preventative and therapeutic strategy. Methods: We analyzed by flow cytometry peripheral blood mononuclear cells (PBMCs) from newly diagnosed DCIS patients for the presence of various immune cell types expressing specific phenotypic markers of immune effectors or immune suppressors and compared them with PBMC from age-matched healthy individuals. Results: We found a statistically significant increase in the frequency of FoxP3+ regulatory T cells in DCIS PBMC compared with healthy controls. There was also a significant increase in Tim-3+CD8+ T effector memory cells (P= 0.035) and Tim-3+ CD8+ NKT cells (P = 0.033) in the PBMCs of patients with DCIS compared with healthy controls. T cells expressing other exhaustion markers, such as PD-1+ and LAG-3+ were present at very low levels in both groups. Conclusion: Our results suggest that some of the many immunosuppressive mechanisms seen in patients with invasive breast cancer, such as regulatory T cells, are already present in pre-cancer DCIS. Evidence of the beginning of immune suppression is also reflected in the increased frequency of CD4+ and CD8+ T cells expressing the exhaustion marker Tim-3. Citation Format: Sedigheh Taghinezhad-S, Amir Hossein Mohseni, Pamela L. Beatty, Leisha A. Emens, Olivera J. Finn. Evidence of immunosuppression in patients with breast ductal carcinoma in situ [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2875.

Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Recurrence in Breast Noninvasive Neoplasia: A 10-Year Follow-Up of TAM-01 Study.

Five-year data of the phase III trial TAM-01 showed that low-dose tamoxifen at 5 mg once daily administered for 3 years in women with intraepithelial neoplasia (IEN) reduced by 52% the recurrence of invasive breast cancer or ductal carcinoma in situ (DCIS), without additional adverse events over placebo. Here, we present the 10-year results. We randomly assigned 500 women with breast IEN (atypical ductal hyperplasia, lobular carcinoma in situ [LCIS], or hormone-sensitive or unknown DCIS) to low-dose tamoxifen or placebo after surgery with or without irradiation. The primary end point was the incidence of invasive breast cancer or DCIS. The TAM-01 population included 500 women (20% atypical ductal hyperplasia, 11% LCIS, and 69% DCIS). The mean (±SD) age at the start of treatment was 54 ± 9 years, and 58% of participants were postmenopausal. After a median follow-up of 9.7 years (IQR, 8.3-10.9 years), 66 breast cancers (15 in situ; 51 invasive) were diagnosed: 25 in the tamoxifen group and 41 in the placebo group (annual rate per 1,000 person-years, 11.3 with tamoxifen v 19.5 with placebo; hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.95; log-rank P = .03). Most recurrences were invasive (77%) and ipsilateral (59%). Regarding contralateral breast cancer incidence, there were six events in the tamoxifen arm and 16 in the placebo arm (HR, 0.36; 95% CI, 0.14 to 0.92; P = .025). The number needed to be treated to prevent one case of breast event with tamoxifen therapy was 22 in 5 years and 14 in 10 years. The benefit was seen across all patient subgroups. There was a significant 50% reduction of recurrence with tamoxifen in the DCIS cohort, which represents 70% of the overall population (HR, 0.50; 95% CI, 0.28 to 0.91; P = .02). No between-group difference in the incidence of serious adverse events was reported during the prolonged follow-up period. Tamoxifen 5 mg once daily for 3 years significantly prevents recurrence from noninvasive breast cancer after 7 years from treatment cessation without long-term adverse events.

Abstract P4-07-41: Is axillary evaluation still necessary in DCIS?

Abstract Background Ductal carcinoma-in-situ (DCIS) is a growing health problem in the world. Before the advent of screening mammography, the incidence of DCIS was low, and patients presented with DCIS that had become clinically symptomatic. Upon this evidence, a strategy of aggressive surgical therapy like the approach with invasive cancer was adopted. The status of the regional lymph nodes is the most important prognostic factor and predictor of survival in breast cancer, but as DCIS is a malignant proliferation of the epithelial inside the breast duct and, therefore, does not have the capacity to generate metastasis. However, an upstaging after surgery is possible. The need for sentinel node biopsy (SNB) in patients with a preoperative biopsy diagnosis of DCIS is still controversial but is done in selected cases. Objectives Our main objective in this study was to evaluate the surgical approach in the axilla (SNB or axillary dissection – AD) of patients diagnosed with DCIS in a single institution and describe the surgical treatment (mastectomy or breast conservative surgery – BCS). In addition, we aimed to find the reasons that led our surgeons to choose one or the other treatment. Methods A retrospective analysis was made using the Pérola Byington Hospital’s database, from January 2011 to December 2019. During this period, 11,373 cases of breast cancer were treated int the institution and 812 (7.4%) were DCIS. Data was available and we could analyze 494 patients who underwent core biopsy or vacuum-guided biopsy guided by mammography or ultrasound and were diagnosed with DCIS and underwent surgical treatment at the Hospital. We grouped the patients into 3 age groups: under 40, 40-49, and 50 and over. In all groups, we had patients who underwent SNB using the patent blue technique or axillary dissection (AD) and were evaluated using the H&amp;E method. We had also evaluated the type of surgery (BCS or mastectomy) in each age group. Results DCIS was diagnosed through mammographic alterations in 62% of all cases and nuclear grade 2 was the most common, with 47%, followed by grade 3 and 1, 46% and 4%, respectively. In 2% of cases the data was missing. Comedonecrosis was present in 78% of our specimens. The type of surgery (radical or BCS) was evaluated and BCS was made in 360 patients (72,87% of the cases), with the axillary approach being performed in 125 patients of these patients (50,20% of cases that went to axillary approach including 9 patients that were submitted to AD). In 27,1% the surgical approach was a radical surgery (total mastectomy or skin sparing mastectomy) and in this group 92,5% were submitted to axillary approach. There was a strong correlation in the type of surgery and axillary approach (p-value 0,000) In the group of patients younger than 40 years, 74% of patients (17 out of 23 in total) underwent an axillary approach regardless of the type of surgery (p-value 0.036) When evaluating the predetermined age groups, we saw that most of our patients were 50 years or more (69%), followed by patients between 40-49 years (26%) and 5% in patients under 40 years. In only 3% of cases (16 in 494) we reclassified the lesion as invasive carcinoma after the surgery. None of them had a lymph node involved by malignant cells after surgery and that’s include the cases reclassified as invasive carcinoma. Conclusion The results obtained in this analysis showing no axillary involvement will make us rethink the indications for the concomitant surgical approach of the breast and the axilla in cases with a diagnosis of DCIS to reduce the axillary surgical overtreatment. It was not our goal to compare the costs, mobility, and complications of the surgical treatment as the survival in these patients that can be addressed in another studies. Citation Format: Marcellus Ramos, Andre Mattar, Andressa Amorim, Felipe Cavagna, Mariana Passos, Raquel Fernandes, Jorge Shida, Luiz Henrique Gebrim. Is axillary evaluation still necessary in DCIS? [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-41.

The clinical significance of HER2 expression in DCIS.

HER2 is an established prognostic and predictive marker for patients with invasive breast cancer. The clinical and biological significance of HER2 overexpression in patients with ductal carcinoma in situ (DCIS) remains poorly defined. DCIS is a heterogeneous disease and some patients with DCIS will not progress to invasive breast cancer. However, clinically significant recurrence rates have been reported after breast-conserving surgery for DCIS and approximately half of these cases will be life-threatening invasive recurrences. Since the incidence of DCIS is rising due to the widespread use of screening mammography, there is robust interest in selecting high-risk DCIS patients that may benefit from adjuvant therapies. Molecular prognostic and predictive models in early invasive breast cancer help clinicians identify patients that will benefit from chemotherapy. Molecular subtyping and profiling could also be useful in treating DCIS patients. According to current practice guidelines, HER2 testing is not recommended in DCIS patients. Nevertheless, evidence suggests that HER2-positive DCIS cases may be associated with adverse clinicopathological parameters and increased recurrence rates. This review summarizes the existing body of evidence linking HER2 expression and ipsilateral breast cancer recurrence in DCIS. HER2, as well as its correlation with other clinicopathological markers might be a useful prognostic and predictive marker, helping clinical decision-making in DCIS patients.

Abstract P3-03-21: Contralateral breast cancers detected by pre-operative MRI in patients diagnosed with DCIS: Whart do they mean?

Abstract Background: For patients with ductal carcinoma in situ (DCIS), data about contralateral breast cancers detected by MRI at primary diagnosis and the impact of MRI use on the incidence and stage of contralateral breast cancers during follow-up are scarce. Methods: We selected all women diagnosed with a primary DCIS in the Netherlands in 2011-2015 from the Netherlands Cancer Registry. The synchronous and metachronous detection of contralateral DCIS and contralateral invasive breast cancer was assessed for patients who did receive an MRI upon primary diagnosis (MRI group) and for an age-matched control group without MRI. Incidence of contralateral disease during follow-up was calculated using competing risk methods.Results: Of the 8486 patients diagnosed with primary DCIS, 1571 (19%) received an MRI. In the MRI group, 0.8% of patients were diagnosed with a synchronous contralateral DCIS and 1.3% with synchronous contralateral invasive breast cancer. Median follow-up time was 6.4 years (IQR: 5.1-7.6). The estimated five-year cumulative incidence of synchronous plus metachronous contralateral DCIS was 2.0% (95% CI: 1.4%-2.8%)) for the MRI group and 0.9% (95% CI: 0.5%-1.5%) for the age-matched control group. The five-year cumulative incidence of contralateral invasive breast cancer was 3.5% (95% CI: 2.7%-4.5%) for the MRI group and 2.3% (95% CI: 1.6%-3.1%) for the age-matched control group. In patients aged &amp;lt;50 years, the cumulative incidence of metachronous contralateral DCIS was statistically significantly higher in the MRI group than in the age-matched controls (sHR= 4.22 (95%CI: 1.19-14.99), P=0.03). This was not the case in patients aged 50-74 years (sHR=0.89 (95%CI: 0.41-1.93), P=0.77). Conclusions: MRI led to more frequent detection of synchronous contralateral invasive breast cancers without lowering the number of metachronous contralateral invasive breast cancers. In patients aged below 50 years, MRI added to conventional imaging led to a persisting higher rate of DCIS diagnosed in the opposite breast, also without influencing the occurrence of invasive breast cancers being detected during the first five years of follow-up. Footnotes Citation Format: Kristien Keymeulen, Sandra Geurts, Loes Kooreman, Lucien Duijm, Sanne Engelen, Sigrid Vanwetswinkel, Ernest Luiten, Sabine Siesling, Adri Voogd, Vivianne Tjan-Heijnen. Contralateral breast cancers detected by pre-operative MRI in patients diagnosed with DCIS: Whart do they mean? [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 P3-03-21.

A Study to Determine the Incidence of Coexisting Carcinoma In situ in Mastectomy Specimens with Invasive Breast Carcinoma

Background: In situ breast carcinoma is a pre-invasive cancer that has not breached the epithelial basement membrane. This was previously a rare but is becoming increasingly common. It may be ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS). DCIS is a precursor of invasive carcinoma, whereas LCIS is not a precursor but only a predictor of invasive carcinoma. In those with LCIS, 50% of the carcinomas occur in the contralateral breast. Aim: This paper aims to study the incidence of DCIS and LCIS in mastectomy specimens of invasive carcinoma breast. Materials and Methods: This is a subjective study of 226 patients in a tertiary care hospital over a period of 18 months. Patients with invasive breast carcinoma undergoing mastectomy were included. Patients with invasive breast carcinoma and those who have undergone any breast surgeries in the past were excluded. The histopathology reports were analysed for finding out DCIS and LCIS coexisting with invasive carcinoma of the breast. Results: The patients had a mean age of 56–11.025 years. 59.7% were in the 41–60-year age group. DCIS coexisted with invasive carcinoma in 28.3% (64). LCIS was absent in all cases of invasive carcinoma. Amongst those with DCIS, high-grade DCIS was found in 65.6% (42) and low-grade DCIS in 34.4% (22). Amongst the DCIS group, comedo type was present in 46.9% (30), followed by cribriform type 31.2% (20), solid type 18.8% (12) and papillary type 3.1% (2). Conclusion: DCIS was found to coexist with invasive carcinoma in 28.3% of cases, whereas LCIS was absent in all cases of invasive carcinoma.

Ductal Carcinoma in Situ: State-of-the-Art Review.

Ductal carcinoma in situ (DCIS) is a nonobligate precursor of invasive cancer, and its detection, diagnosis, and management are controversial. DCIS incidence grew with the expansion of screening mammography programs in the 1980s and 1990s, and DCIS is viewed as a major driver of overdiagnosis and overtreatment. For pathologists, the diagnosis and classification of DCIS is challenging due to undersampling and interobserver variability. Understanding the progression from normal breast tissue to DCIS and, ultimately, to invasive cancer is limited by a paucity of natural history data with multiple proposed evolutionary models of DCIS initiation and progression. Although radiologists are familiar with the classic presentation of DCIS as asymptomatic calcifications at mammography, the expanded pool of modalities, advanced imaging techniques, and image analytics have identified multiple potential biomarkers of histopathologic characteristics and prognosis. Finally, there is growing interest in the nonsurgical management of DCIS, including active surveillance, to reduce overtreatment and provide patients with more personalized management options. However, current biomarkers are not adept at enabling identification of occult invasive disease at biopsy or accurately predicting the risk of progression to invasive disease. Several active surveillance trials are ongoing and are expected to better identify women with low-risk DCIS who may avoid surgery.

Ductal Carcinoma In Situ - Quo Vadis?

The introduction of mammographic screening in the early 1980's was associated, in the three following decades, with a dramatic increase in the detection of ductal carcinoma in situ (DCIS), pathology rarely detected before, on surgical specimen, at the periphery of an invasive cancer (1,2,3). It is estimated that in the United States the incidence of DCIS, each year, varies between 18 to 25% of the total number of newly diagnosed breast cancers (4,5). Ductal carcinoma in situ belongs, genetically and pathomorphologically, to a heterogenous group of preinvasive neoplastic lesions characterized by clonal proliferation of malignant cells limited to the lumen of breast ducts. It has not a known natural history and its phenotypical spectrum is wide, varying from a slowly evolving disease to a fast growing one, invading the surrounding stroma and even metastasizing to distant sites (6). In the absence of reliable prognostic markers, most of patients are submitted to invasive treatments consisting mainly in surgery, alone or associated with radiation and endocrine therapy (7). Molecular subtyping has improved the understanding of breast cancer biology and its possibilities for evolution and have provided the tools to design a more personalized treatment (8). In the absence of reliable molecular markers clinical management of patients with DCIS is based on patient's option and tumor characteristics. Based on the knowledge of today, DCIS could be used to exemplify the notions of overdiagnosis and overtreatment. The final goal of the treatment of DCIS is to prevent invasive breast cancer recurrence. Mortality rate associated with DCIS is very low, being estimated at 1-2 % at 10 years, while patients with DCIS treated by wide local excision with or without radiation may have a local recurrence rate of 5 to 30% and half of these present as an invasive cancer. Today's clinicians are not able to predict the risk of progression for a DCIS diagnosed by biopsy, but neither the risk of local recurrence, as an invasive cancer, of DCIS treated by conservative surgery with or without radiation (9). Progression to invasive cancer is difficult to be predicted as the disease is highly heterogenous. Because of these uncertainties, it is highly important to carefully inform the patient and engage her in the treatment decision process (10). There is a trend for de-escalation of treatment for DCIS. A study comparing two groups of patients with pure DCIS was conducted: one with standard care and the other under active surveillance (11). The main outcome was the probability to die from breast cancer at 10 years after the diagnosis. The mortality risk from breast cancer is higher for younger women, than the older ones, under active surveillance. Women over the age of 70 years, have many comorbidities that could induce the risk of dying, regardless of DCIS treatment decision. This study suggested that active surveillance could be a reasonable option for certain category of patients. This attitude is not without risks. A patient with DCIS on core needle biopsy could hide an invasive cancer in 25% of cases (12). Today, there are four randomized control trials of active surveillance offered to patients with low-grade DCIS: LORD (LOw Risk DCIS), COMET (Comparison of Operative to Monitoring and Endocrine Therapy), LORIS (LOw RISk DCIS) and LORETTA (10,13-16). Non-surgical approaches are of two types: active surveillance alone or associated with hormone therapy. There are some differences between the trials. While in LORD and LORIS trials the study arms are represented by active surveillance only, hormone therapy is an option in COMET trial and mandatory in the single arm trial LORETTA. The aim of these studies is to examine the safety and the effectiveness of active surveillance compared with surgical management for low-risk DCIS. The results of these trials are awaited with great interest. Patients with ductal carcinoma in situ need special counseling. To talk about "a good" cancer or even no cancer and to recommend as treatment a mastectomy is highly confusing. The language used by all members of the team must be unitary, removing the anxiety and helping patients to make the best decision. This special issue is a great opportunity to have the opinions of highly respected international specialists in the field for a comprehensive review of DCIS of the breast.

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.

Ductal carcinoma in situ (DCIS)—precision medicine for de-escalation

Most women undergoing breast conservation surgery (BCS) for ductal carcinoma in situ (DCIS) receive breast radiotherapy (RT) to reduce the incidence of ipsilateral recurrent DCIS and development of invasive disease. This review seeks to appraise the potential for de-escalation of RT based on clinical, biomarker, and/or molecular testing. Clinical prognostic factors have highlighted young age, tumor (DCIS) size, multifocality, DCIS grade, palpability, and immunohistochemical biomarkers (ER negative, HER2 positive) as prognostic factors. However, molecular markers including the Oncotype DCIS molecular assay alongside clinical factors and most recently the DCISionRT tool incorporating several biomarkers with clinical prognostic factors each appear to have the potential to guide clinical decision-making for the omission of RT. Refinements of these de-escalation tools are continuing. Conversely, markers to demonstrate which patients most need RT, which will then be effective to prevent further disease, are currently lacking. Selection of patients undergoing BCS for DCIS who might be suitable for de-escalation (omission) of RT has improved beyond use of a few clinical features to be guided by biomarker and molecular testing.

Ductal carcinoma in situ and the extent of surgery

Introduction: Ductal carcinoma in situ (DCIS) is a very heterogenous disease. The incidence of DCIS has been increasing with the adoption of mammography screening. This opened new questions concerning surgical and adjuvant therapy. Methods: We retrospectively observed the incidence of DCIS amongst the patients that underwent surgical resection in EUC clinic Zlín between 2017 and 2019. We also assessed the extent of breast surgery including interventions in axilla and the adjuvant therapy. Results: There were 616 breast cancer patients, of whom 44 (7.1%) were diagnosed with DCIS. Breast-conserving surgery was performed in 35 (80%) patients. Lumpectomy alone was performed in 21 (47%) patients. Mastectomy was indicated primarily in 9 cases with additional two mastectomies performed to achieve clear margins. All sentinel nodes were negative. Conclusion: Results confirmed, that the surgical therapy as well as radiotherapy and hormonal treatment are performed according to guidelines at our department. Proportion of sentinel node biopsy is remarkably higher, therefore an improvement in this area is our next goal.

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.

Evaluating axillary management and re-excision rates of Ductal Carcinoma in Situ (DCIS) at a London district general hospital

Background: Ductal carcinoma in situ (DCIS) is a premalignant breast lesion without metastatic potential. Since the implementation of the national breast cancer screening programme in the UK, the incidence of DCIS has increased; now representing 12% of all breast cancers, with more than 7000 new cases per year in the UK. Under National Institute for Health and Care Excellence (NICE) guidelines [NG101] 2018, it is clear that routine sentinel lymph node biopsy is not recommended for DCIS when managed with breast conserving surgery.

Ductal Carcinoma In Situ in Pregnant Women.

Breast cancer is the second most common malignancy affecting pregnant women. Ductal carcinoma in situ (DCIS) during pregnancy has not been well described with limited literature addressing the optimal treatment options. This is important topic as the incidence of pregnancy-associated breast cancer (PABC) has been increasing. In the United States, 1 in 3000 pregnancies are complicated by breast cancer diagnosis. Most DCIS are screen detected as most patients are asymptomatic. Since routine screening mammogram is not recommended during pregnancy, diagnosis of DCIS without invasive disease is uncommon diagnosis. Although PABC is reported to account for 0.2-3.8% of all newly diagnosed breast cancer, it has not been defined between the diagnosis of DCIS or invasive breast cancer making true incidence of DCIS in pregnancy difficult to report. This review summarizes multidisciplinary recommendations for optimal treatment for DCIS diagnosed during pregnancy.

Estimating the natural progression of non-invasive ductal carcinoma in situ breast cancer lesions using screening data.

In addition to invasive breast cancer, mammography screening often detects preinvasive ductal carcinoma in situ (DCIS) lesions. The natural progression of DCIS is largely unknown, leading to uncertainty regarding treatment. The natural history of invasive breast cancer has been studied using screening data. DCIS modeling is more complicated because lesions might progress to clinical DCIS, preclinical invasive cancer, or may also regress to a state undetectable by screening. We have here developed a Markov model for DCIS progression, building on the established invasive breast cancer model. We present formulas for the probability of DCIS detection by time since last screening under a Markov model of DCIS progression. Progression rates were estimated by maximum likelihood estimation using BreastScreen Norway data from 1995-2002 for 336,533 women (including 399 DCIS cases) aged 50-69. As DCIS incidence varies by age, county, and mammography modality (digital vs. analog film), a Poisson regression approach was used to align the input data. Estimated mean sojourn time in preclinical, screening-detectable DCIS phase was 3.1 years (95% confidence interval: 1.3, 7.6) with a screening sensitivity of 60% (95% confidence interval: 32%, 93%). No DCIS was estimated to be non-progressive. Most preclinical DCIS lesions progress or regress with a moderate sojourn time in the screening-detectable phase. While DCIS mean sojourn time could be deduced from DCIS data, any estimate of preclinical DCIS progressing to invasive breast cancer must include data on invasive cancers to avoid strong, probably unrealistic, assumptions.