Grade Ductal Carcinoma In Situ Research Articles

Abstract PO5-13-11: Quantitative Assessment of HER2 Expression in Intraductal Neoplasms of the Breast

Abstract HER2 (ERBB2) is an established prognostic and predictive marker for patients with invasive breast cancer and used in HER2-targeted therapy. The clinical and biological significance of expression of HER2 protein in patients with intraductal neoplasms of the breast is not well characterized. In this study, we used our HS-HER2 (High Sensitivity-HER2) which is a CAP/CLIA certified laboratory derived test (LDT) using quantitative immunofluorescence (QIF). We evaluated HER2 expression in DCIS (ductal carcinoma in situ), LCIS (lobular carcinoma in situ) and benign lesions to correlate with their clinicopathologic characteristics. Thirty- eight cases of DCIS, and fourteen cases of LCIS and thirty benign cases were selected from the Yale Pathology department archives and 252 ROIs (regions of interest) were annotated by a board-certified pathologist. DCIS is classified according to the three-tier nuclear grading system: low, intermediate, and high-nuclear grade. LCIS is classified as PLCIS (pleomorphic variant) and CLCIS (classic LCIS) according to the WHO classification of breast tumors. Serial sections of FFPE tumor specimens were used to accurately quantify the HER2 expression by the HS-HER2 assay and the acquisition by QuPath v.04 with Qymia extension. According to the LOD (limit of detection,3 amol/mm2), LOQ (limit of quantification, 9 amol/mm2) and LOL (limit of linearity, 23 amol/mm2) of the optimized HS-HER2 assay as performed in our CLIA lab shows a broad range of HER2 expression in both DCIS and LCIS lesions, ranging from 0.7 amol/mm2 to 111.4 amol/mm2 in DCIS and 3.6 amol/mm2 to 49.9 amol/mm2 in LCIS. High grade DCIS lesions express higher average HER2 levels (111.4 + 0.7 amol/mm2) than combined low and intermediate grade DCIS (77.9 +1.9 amol/mm2) with no significant difference between low/intermediate and high-grade DCIS. CLCIS lesions express higher average HER2 level (49.9 + 3.6 amol/mm2) than PLCIS (35.1 + 5.4amol/mm2) but again this is not statistically significant. HER protein expression is relatively low in benign lesions ranging from 0.8 to 8.4 amol/mm2. Using the HS-HER2 assay, our results show quantitative level HER2 levels in DCIS and LCIS breast lesions. These findings may be important as HER2 targeted therapies that work in gene-unamplified cancer (HER2 conjugated ADCs) gain broader usage in the clinic. Citation Format: Nay Nwe Nyein Chan, Haiying Zhan, Revekka Khaimova, Thazin Aung, Charles Robbins, Patricia Gaule, David Rimm. Quantitative Assessment of HER2 Expression in Intraductal Neoplasms of the Breast [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 PO5-13-11.

Abstract PO3-28-10: MRI Radiomic phenotypes derived from the ECOG-ACRIN E4112 Trial to assess high-risk ductal carcinoma in situ

Abstract INTRODUCTION Ductal carcinoma in situ (DCIS) is a non-lethal pre-invasive breast cancer that can co-exist with invasive disease. Dynamic contrast-enhanced (DCE) MRI is sensitive for the detection of high-grade DCIS and invasive cancer while Oncotype DCIS Score is a 12-gene assay that can assess recurrence risk. In practice, it is difficult to distinguish low- from high-risk DCIS, which leads to overtreatment for up to half of women diagnosed with DCIS. We hypothesize that radiomic phenotypes of DCIS derived from DCE-MRI data may serve as prognostic markers to improve risk stratification by capturing disease heterogeneity. Here we evaluate the ability of these phenotypes to predict DCIS Score and upstaging of DCIS to invasive disease on wide local excision in a multicenter trial. METHODS Data: DCE-MRI data from the ECOG-ACRIN E4112 trial were retrospectively analyzed. Primary analysis focused on participants with data on disease upstaging (N=295), with secondary analysis in a subset (N=174) of participants with DCIS Scores (dichotomized as >55 and 55) and pure DCIS. Clinical information included patient demographics, lesion morphology on MRI, background parenchymal enhancement, DCIS grade, central necrosis, and hormone receptor status. Data analysis: Radiologist-drawn lesion segmentations and publicly available software, CaPTk, were used to compute 64 radiomic features from first post-contrast images for each participant. Radiomic phenotypes were identified using hierarchical clustering on the extracted features. A Chi-square test was used to evaluate the association between radiomic phenotypes and each outcome. The likelihood ratio test was used to compare two logistic regression models: 1)clinical model using only clinical information as predictors and 2) clinical+phenotypes model using clinical information and phenotype assignment as predictors. Each model was used for the prediction of upstaging to invasive disease and DCIS score. Model performance was evaluated as the 10-fold cross-validated area under the receiver operator characteristic curve (AUC). A p< 0.05 was considered significant. RESULTS A total of 45 (15%) cases upstaged to invasive disease. Two radiomic phenotypes were identified: Phenotype 1 indicated greater lesion signal heterogeneity, while Phenotype 2 indicated lower heterogeneity. Radiomic phenotype was strongly associated with disease upstaging (p=0.0034) – with a higher rate of upstaging for Phenotype 1 – but not with DCIS score (p=0.1174, Table 1). For predicting disease upstaging, the clinical+phenotypes model yielded a higher AUC=0.72 and a significantly better fit to the data (p=0.0022) compared to the clinical model parameterized by clinical information alone (AUC=0.69). For predicting DCIS Score, the clinical+phenotypes model (AUC=0.77) showed similar performance compared to the clinical model (AUC=0.76) and no significant improvement in fit to the data (p=0.2920). CONCLUSION Radiomic phenotypes capturing disease heterogeneity show promise as prognostic predictors for predicting disease upstaging in DCIS compared to clinical information alone and may enable more efficient disease management. We observed that phenotypes did not have independent predictive outcome for DCIS score, suggesting that MRI and DCIS Score offer independent information and could be combined in future models to better predict disease recurrence or progression. Clinical applications of radiomic phenotypes may improve risk stratification and potentially result in decreased overtreatment of women diagnosed with DCIS. Table 1: Association between radiomic phenotypes and DCIS outcomes using a Chi square test. Citation Format: Kalina Slavkova, Ruya Kang, Vivian Belenky, Anum Kazerouni, Debosmita Biswas, Hannah Horng, Rhea Chitalia, Michael Hirano, Jennifer Xiao, Ralph Corsetti, Sarah Javid, Derrick Spell, Antonio Wolff, Joseph Sparano, Seema Khan, Christopher Comstock, Justin Romanoff, Jon Steingrimsson, Constantine Gatsonis, Constance Lehman, Savannah Partridge, Despina Kontos, Habib Rahbar. MRI Radiomic phenotypes derived from the ECOG-ACRIN E4112 Trial to assess high-risk ductal carcinoma in situ [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 PO3-28-10.

Abstract PO2-28-07: Artificial Intelligence-based Computer-aided Diagnosis for Mammography: Predicting Occult Invasive Cancer in Women with Biopsy-proven Ductal Carcinoma in Situ

Abstract Background: Ductal carcinoma in situ (DCIS) is a noninvasive breast cancer confined within the basement membrane. Due to the increase in breast cancer screening, DCIS is increasingly being diagnosed on biopsy. Active surveillance is a novel and evolving treatment strategy for DCIS to reduce overtreatment. Currently ongoing clinical trials of active surveillance include only mammographic findings in their eligibility criteria, however mammography has limited ability to detect occult invasive cancer. The objective of this study was to investigate whether an artificial intelligence-based computer-aided diagnosis (AI-CAD) application for mammography can improve the prediction of occult invasive cancer in women with percutaneous needle biopsy-proven DCIS. Methods: A retrospective search of our database identified consecutive women with percutaneous needle biopsy-proven DCIS who underwent surgery at Seoul National University Hospital (Seoul, Korea) between June 2019 and May 2021. Two board-certified breast radiologists reviewed preoperative mammographic findings of the primary tumor in consensus according to the Breast Imaging Reporting and Data System. Using a commercially available AI-CAD (Lunit INSIGHT for Mammography, Lunit Inc.), quantitative abnormality scores of 0 to 100% of the ipsilateral breast were obtained. Data were collected on age at diagnosis, symptoms, biopsy methods, DCIS grade on biopsy, and presence or absence of invasive cancer and axillary lymph node metastases on surgical pathology. Multivariable logistic regression models were used to evaluate factors associated with prediction of occult invasive cancer. Results: Of 692 biopsy-proven DCIS in 692 women (mean age, 53 years ± 11 [standard deviation]), 298 (43%) presented as calcifications only, 160 (23%) as mass or asymmetry, and 111 (16%) as masses with calcifications. The other 123 (18%) cancers were not demonstrable on mammography. Surgical pathology revealed occult invasive cancer in 278 (40%) women and 18 (3%) had axillary metastasis. Women with occult invasive cancer showed higher abnormality scores on AI-CAD than women with pure DCIS (mean, 70% vs. 51%; P < .001), and women with axillary metastasis had higher abnormality scores on AI-CAD than women without axillary metastasis (mean, 88% vs. 58%; P = .002). High ( >75%) abnormality score on AI-CAD (Odds ratio [OR], 1.8 [95% CI: 1.3, 2.6]; P < .001), age of 55 years or higher (OR, 1.6 [95% CI: 1.2, 2.3]; P =.005), present symptoms in the ipsilateral breast (OR, 2.7 [95% CI: 1.9, 4.0]; P < .001), biopsy performed with a 14-gauge automated gun (OR, 2.5 [95% CI: 1.7, 3.6]; P < .001), and high-grade DCIS at biopsy (OR, 2.5 [95% CI: 1.7, 3.5]; P < .001] were independent predictors of occult invasive cancer with a C-index of 0.75 (95% CI: 0.72, 0.78). Conclusion: The quantitative score of preoperative mammography obtained from a commercially available AI-CAD was able to predict occult invasive cancer in an easy and simple manner. AI-CAD applications for preoperative mammography may be useful in predicting occult invasive cancer in women with biopsy-proven DCIS, especially in those without preoperative breast MRI. Citation Format: Su Hyun Lee, Hajung Kim, Su Min Ha, Soo-Yeon Kim, Jung Min Chang, Nariya Cho, Woo Kyung Moon. Artificial Intelligence-based Computer-aided Diagnosis for Mammography: Predicting Occult Invasive Cancer in Women with Biopsy-proven Ductal Carcinoma in Situ [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 PO2-28-07.

Abstract PO4-25-10: Towards personalized medicine for DCIS - the role of hormone receptors, HER2, and Ki67 status in high-grade DCIS

Abstract Objective: This study aimed to investigate the molecular details in breast ductal carcinoma in situ (DCIS). Expression status of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 were investigated among luminal A (LumA), luminal B HER2-negative (LumB HER2-), luminal B HER2-positive (LumB HER2+), HER2-enriched, and triple-negative (TPN), subtypes of DCIS. Materials & Methods: The study comprised formalin-fixed paraffin-embedded (FFPE) specimens of 357 DCIS grade 3 cases diagnosed between 1996 – 2018. Routine diagnostic immunohistochemical (IHC) staining were performed. DCIS cases were classified as LumA, LumB HER2-, LumB HER2+, HER2-enriched or TPN, according to the 2013 St. Gallen guidelines, which is used for molecular subtyping of invasive breast carcinoma (IBC). Each subtype was sorted into three subcategories: “pure” meaning those without an invasive component; “w/invasive” meaning those with an invasive component; and “all” meaning the entire group of the given subtype. Furthermore, ER and PR-receptor expression was registered for LumA, LumB HER2- and LumB HER2+ cases as intervals. The distribution of Ki67 was analyzed within each subtype. For some analyses, we combined the LumA and LumB HER2- subtypes into one entire group. The inter-observer variability of Ki67 was calculated by setting a cut-off value of 20% (2013 St. Gallen). A cohort (n = 47) of DCIS cases with a median Ki67 value of 18% was selected. Ki67 was calculated by analyzing 200 DCIS cells in two separate hotspots. Cohen's Kappa coefficient was calculated based on these data. HER2 (IHC) was scored based on ASCO/CAP guidelines established for routine diagnostic work-up for IBC. 16 equivocal cases (2+) were further investigated using dual SISH. Results: 98% of “all” cases of the LumA subtype showed an ER ≥ 50%. PR expression ≥ 50% was found in 91% of cases in this subtype. The incidence of ER-receptor at a cut-off ≥ 50% in the LumA subtype was significantly higher than that in the LumB HER2- and LumB HER2+ subtypes (p < 0.0001, Chi-square). In contrast, there was a statistically significant reduction in ER-receptor expression at a cut-off < 10% in LumA compared to the latter subtypes. The proportion of cases with PR-receptors with a cut-off of < 20% showed significant differences between LumA, LumB HER2- and LumB HER2+ subtypes (1.6%; 47% and 37%, respectively). There was also a significantly higher proportion of PR-receptor ≥ 50% cases among the LumA subtype. We found a significant association between PR < 20% and HER2 (3+) in luminal subtypes (p < 0.0004, Fisher's exact). There was no significant difference in ER/PR expression in “pure” cases of luminal subtypes of DCIS versus those with an invasive component (p = 0.1831, Chi-square). The Ki67 in the entire population (n = 357) varied from < 1% to > 80%. The mean and median were around 20% in those subtypes whose classifications were not depended on Ki67. There was a significant difference in the distribution of Ki67 when cases of LumA “all” and those of LumB HER2- “all” were combined as one entire group and were compared to LumB HER2+ “all” and HER2-enriched “all” (p-adjusted < 0.0001, Kruskal Wallis). The assessment of Ki67 among different observers showed a Cohen's kappa coefficient of 0.29 – 0.31 (fair agreement). We compared the HER2 (IHC) 0, 1+ and 2+ score among LumA and LumB HER2- subtypes and did not find a statically significant difference, when the “pure” and “w/invasive” were compared (p = 0.603, Chi-square). Conclusions: Ki67 was highly variable in DCIS grade 3. Inter-observer agreement was (as expected) suboptimal, and the cut-off at 20% defined by the 2013 St Gallen guidelines for IBC is not reliable for the distinction of LumA and LumB HER2 subtypes of DCIS. The LumB subtype of DCIS is heterogeneous with considerable variability among the four IHC markers used in the present study. A low PR is strongly associated with HER2 (3+), in luminal subtypes (p < 0.0004, Fisher's exact). Citation Format: Hossein Schandiz, Lorant Farkas, Daehoon Park, Solveig Norheim Andersen, Jürgen Geisler, Torill Sauer. Towards personalized medicine for DCIS - the role of hormone receptors, HER2, and Ki67 status in high-grade DCIS [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 PO4-25-10.

Abstract PS01-10: Surgical margins in breast conserving surgery (BCS) for ductal carcinoma in-situ (DCIS) and clinical outcomes: significant associations with increased recurrence and overall survival

Abstract Background: Optimal surgical margin in breast conserving surgery (BCS) for DCIS are not established, largely due to an absence of accurate margin data. A margin width of 2mm was adopted by the American College of Surgeons (ACS). The UK Association of Breast Surgery (ABS) recommended a 1mm margin. Conducting a randomized controlled trial to answer this question is unfeasible; therefore we used retrospective histological margin data from available datasets to assess whether there is an association between margin width and time to recurrence (TTR). Methods: Patients were included if aged >18 years with a new diagnosis of DCIS alone, between 2003-2014, within UK NHS Breast Screening Programme (BSP). Primary treatment included BCS and a minimum histological excision margin width recorded. Exclusion criteria included: i) prior history of DCIS; ii) prior history of invasive cancer or its diagnosis within 3 months of initial surgical treatment for DCIS. Data was extracted from English Cancer Registries (CR), ABS and Sloane audits. TTR was defined as time from diagnosis to local or distant recurrence. Cox regression was used to compare TTR by surgical margin width utilising a range of thresholds, with focus on < 1mm vs ≥1mm; < 2mm vs ≥2mm and ≥1- < 2mm vs ≥2mm. Patients with 0mm margin or where categorized as “clear/not stated” were excluded from these analyses. Models were adjusted for age group, DCIS grade and size, ER status, number of BCSs, radiotherapy (RT) received, diagnosis year and CR centre. Overall survival (OS) was a secondary endpoint. Results: 17,260 patients diagnosed with DCIS having BCS as definitive surgery were identified between 2003-2014; 679 (5%), 2105 (15%), 1339 (10%) and 9744 (70%) with recorded margins of >0- < 1mm, ≥1- < 2mm, ≥2- < 3mm and ≥3mm, respectively. 10,253 (59%) patients received RT and in 7,007 (41%) RT receipt was unknown. Overall, 14,004 (81%), 3,052 (18%) and 201 (1%) patients had one, two and ≥3 BCSs respectively; there was no significant change in these percentages over time (p=0.2 Cuzick test). Median follow-up time for the cohort was 8.2 years (IQR: 6.1-11.2). 2221 (13%) patients had a subsequent event: 1741/2221 (78%) invasive recurrence and 480/2221 (22%) DCIS alone. The annual event rate over 15 years of follow-up was relatively consistent at 1.2% per annum (pa) for margins ≥2mm versus 1.8% pa for margins < 2mm. A shorter TTR was observed for patients with surgical margins < 1mm vs ≥1mm (adjusted HR=1.30; 95%CI: 1.05-1.62; p=0.02); < 2mm vs ≥2mm (adjusted HR=1.20; 95%CI: 1.06-1.36; p=0.004) and ≥1- < 2mm vs ≥2mm (adjusted HR=1.20; 95%CI: 1.04-1.40; p=0.02). Margins >2mm did not appear to significantly improve TTR (adjusted HR=0.96; 95%CI: 0.85-1.08; p=0.50 for ≥5mm vs ≥2- < 5mm). Models also showed that risk of recurrence increased as the number of BCSs increased (adjusted HR=1.25; 95%CI: 1.10-1.43: p< 0.001 for 2 vs 1 and adjusted HR=2.03; 95%CI: 1.36-3.03: p< 0.001 for 3+ vs 1). In total, 1552 (9%) patients had died. OS appeared reduced for patients with surgical margins < 2mm vs ≥2mm (adjusted HR=1.25 (1.07-1.45); p=0.005) and for ≥1- < 2mm vs ≥2mm (adjusted HR=1.28 (1.07-1.54); p=0.008). Margins <2mm did not appear to significantly improve OS further (adjusted HR=1.06; 95%CI: 0.92-1.21; p=0.43 for ≥5mm vs ≥2- < 5mm). Conclusion: Patients with DCIS with histological margins of < 2mm, adjusted for other clinical factors, have significantly worse TTR and OS rates compared to margins ≥2mm; the increased annual event rate is consistent out to 15 years. More than 1 BCS is also associated with an increased risk of recurrence. These findings are important for the treatment of patients with DCIS. Citation Format: John Robertson, D Mark Sibbering, Sikhuphukile Ndebele-Mahati, Olive Kearins, Sarah Pinder, Ashu Gandhi, Judith Bliss, Lucy Kilburn. Surgical margins in breast conserving surgery (BCS) for ductal carcinoma in-situ (DCIS) and clinical outcomes: significant associations with increased recurrence and overall survival [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 PS01-10.

Abstract PO4-21-01: Recurrent Desmoid Tumor and Ductal Carcinoma In Situ in an African-American Woman: A Case Report and Discussion on Disparities for These Two Cancer Subtypes

Abstract Introduction: Disparities in cancer care in patients from different races and ethnicities unfortunately do exist and are well described in literature. Hormonal-driven cancers, such as some soft-tissue tumors and DCIS, have been demonstrated to impact African-American women (AAW) disproportionately. These patients are at increased risk for not only development of these cancers, but also experience disparities in survival, treatment outcomes, and modalities of treatment. Clinical Case: A 47-year-old premenopausal AAW with past medical history of recurrent desmoid sarcoma of the abdomen and ductal carcinoma in-situ (DCIS) of the left breast presented to oncology clinic with recurrent abdominal mass. The patient was originally diagnosed with DCIS in the left breast in 2018 and subsequently underwent left breast mastectomy with TRAM reconstruction and fat graft later that year. In 2020, the patient noticed a left lower abdominal growth that quickly enlarged and became painful. She underwent imaging without biopsy and was taken to surgery in April 2021 with tumor removal and mesh placement. Pathology showed desmoid fibromatosis infiltrating skeletal muscle and involving the inked resection margin of the specimen. Conservative re-excision and additional therapy was recommended but not done at the time. In 2022, the patient had resection of the area again with pathology of the incisional scar showing skin and deep soft tissue foci suspicious for recurrent desmoid fibromatosis extending to the inked deep margin. No mesh was placed, and the wound closed almost completely. The patient was not aware of positive margins at the time. In January 2023, patient again notice a new bump that was bothersome. Initial CT and MRI without finding of defined mass, but with right rectus thickening and enlarged right external iliac lymph node. Core biopsy in June 2023 confirmed recurrent desmoid fibromatosis. In April 2023, annual screening with mammogram was performed with a finding of 2.9 cm cluster of heterogenous calcification in the right breast. Diagnostic mammogram and ultrasound performed. Core needle biopsy was subsequently performed in May with pathology consistent with high grade DCIS with low ER and PR positivity. Lymph node biopsy was negative, but clinically positive. She is currently undergoing further genetic testing with surgical workup for mastectomy. Discussion and Conclusion: AAW diagnosed with DCIS have higher all-cause and disease specific mortality in comparison to white women (WW) diagnosed with DCIS. AAW are also at increased risk of aggressive secondary breast cancers in both the ipsilateral and contralateral breast in comparison to other races. In regards to tumor biology, WW have been shown to have higher ER and PR positivity in both primary and primary breast cancers than AAW. In many of these large-scale studies higher mortality, recurrence, and metastasis in AAW have been identified regardless of treatment modality. Research into differences in treatment between AAW and WW has shown that AAW, in contrast to our patient case, are more likely to undergo endocrine and radiation therapy rather than mastectomy. Although there does not seem to be an increased risk of desmoid fibromatosis in AAW when compared to WW, other soft-tissue tumors and malignancies do show a predilection for AAW. Incidence of sarcoma in black patients is higher than white patients, and black patients also have poorer survival outcomes. This case provides an example of the intersectionality of two cancer subtypes that impact black patients disproportionately. More evidence is required to unearth the reasons why these two cancer subtypes which are driven by similar processes impact AAW to a greater degree. Citation Format: Vinita Akula, Jessica Jones. Recurrent Desmoid Tumor and Ductal Carcinoma In Situ in an African-American Woman: A Case Report and Discussion on Disparities for These Two Cancer Subtypes [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 PO4-21-01.

Immune cell infiltrate in ductal carcinoma in situ and the risk of dying from breast cancer: case-control study.

Studies identifying risk factors for death from breast cancer after ductal carcinoma in situ (DCIS) are rare. In this retrospective nested case-control study, clinicopathological factors in women treated for DCIS and who died from breast cancer were compared with those of patients with DCIS who were free from metastatic disease. The study included patients registered with DCIS without invasive carcinoma in Sweden between 1992 and 2012. This cohort was linked to the National Cause of Death Registry. Of 6964 women with DCIS, 96 were registered with breast cancer as cause of death (cases). For each case, up to four controls (318; women with DCIS, alive and without metastatic breast cancer at the time of death of the corresponding case) were selected randomly by incidence density sampling. Whole slides of tumour tissue were evaluated for DCIS grade, comedo necrosis, and intensity of periductal lymphocytic infiltrate. Composition of the immune cell infiltrate, expression of oestrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and proliferation marker Ki-67 were scored on tissue microarrays. Clinical information was obtained from medical records. Information on date, site, and histological characteristics of local and distant recurrences was obtained from medical records for both cases and controls. Tumour tissue was analysed from 65 cases and 195 controls. Intense periductal lymphocytic infiltrate around DCIS was associated with an increased risk of later dying from breast cancer (OR 2.21. 95% c.i. 1.01 to 4.84). Tumours with more intense lymphocytic infiltrate had a lower T cell/B cell ratio. None of the other biomarkers correlated with increased risk of breast cancer death. The immune response to DCIS may influence the risk of dying from breast cancer.

Sonography-based multimodal information platform for identifying the surgical pathology of ductal carcinoma in situ

BackgroundThe risk of ductal carcinoma in situ (DCIS) identified by biopsy often increases during surgery. Therefore, confirming the DCIS grade preoperatively is necessary for clinical decision-making. PurposeTo train a three-classification deep learning (DL) model based on ultrasound (US), combining clinical data, mammography (MG), US, and core needle biopsy (CNB) pathology to predict low-grade DCIS, intermediate-to-high-grade DCIS, and upstaged DCIS. Materials and MethodsData of 733 patients with 754 DCIS cases confirmed by biopsy were retrospectively collected from May 2013 to June 2022 (N1), and other data (N2) were confirmed by biopsy as low-grade DCIS. The lesions were randomly divided into training (n=471), validation (n=142), and test (n = 141) sets to establish the DCIS-Net. Information on the DCIS-Net, clinical (age and sign), US (size, calcifications, type, breast imaging reporting and data system [BI-RADS]), MG (microcalcifications, BI-RADS), and CNB pathology (nuclear grade, architectural features, and immunohistochemistry) were collected. Logistic regression and random forest analyses were conducted to develop Multimodal DCIS-Net to calculate the specificity, sensitivity, accuracy, receiver operating characteristic curve, and area under the curve (AUC). ResultsIn the test set of N1, the accuracy and AUC of the multimodal DCIS-Net were 0.752–0.766 and 0.859–0.907 in the three-classification task, respectively. The accuracy and AUC for discriminating DCIS from upstaged DCIS were 0.751–0.780 and 0.829–0.861, respectively. In the test set of N2, the accuracy and AUC of discriminating low-grade DCIS from upstaged low-grade DCIS were 0.769–0.987 and 0.818–0.939, respectively. DL was ranked from one to five in the importance of features in the multimodal-DCIS-Net. ConclusionBy developing the DCIS-Net and integrating it with multimodal information, diagnosing low-grade DCIS, intermediate-to high-grade DCIS, and upstaged DCIS is possible. It can also be used to distinguish DCIS from upstaged DCIS and low-grade DCIS from upstaged low-grade DCIS, which could pave the way for the DCIS clinical workflow.

Cytomorphological Assessment in Aspirates of Ductal Carcinoma in situ: Correlations with Histopathologic Grade, Architectural Pattern, and Invasion

Introduction: Fine-needle aspiration biopsy (FNAB) of the breast is an effective and widely adopted diagnostic technique. Histopathologic grading of ductal carcinoma in situ (DCIS) has prognostic significance. In this current study, FNAB of DCIS was reviewed to identify parameters that predict grading, histopathologic architecture, and presence of invasion in DCIS. Methods: Aspirates from histopathology-proven cases of DCIS were retrieved and reviewed for cytomorphologic parameters including cellularity, composition, epithelial fragment architecture cellular/nuclear features. Results: In total 104 aspirates were reviewed. Cytopathologic cellular features – large nuclear size (p = 0.005), prominent nucleoli (p = 0.011), increased nuclear membrane irregularity (p = 0.043), high variation in nuclear size (p = 0.025), and presence of apoptotic figures in epithelial structures (p < 0.001); and background debris (p = 0.033) correlated with a high-grade diagnosis. Cytoplasmic vacuolation (p = 0.034) was seen exclusively in non-high-grade aspirates. Epithelial fragment architecture did not correlate with grading. A predominance (≥50%) of solid aggregates and papillary fragments on FNAB correlated with histopathologically solid (p = 0.039, p = 0.005) and papillary (p = 0.029, < p = 0.001) patterns. No parameter showed correlation with invasion. Conclusion: FNAB is effective in predicting DCIS grading. Epithelial fragment architecture assessment is limited to papillary or solid types, and FNAB cannot predict focal invasion in DCIS.

Association of DCIS size and margin status with risk of developing breast cancer post-treatment: multinational, pooled cohort study

ObjectiveTo examine the association between size and margin status of ductal carcinoma in situ (DCIS) and risk of developing ipsilateral invasive breast cancer and ipsilateral DCIS after treatment, and stage...

The natural history of ductal carcinoma in situ (DCIS) in simulation models: A systematic review.

Assumptions on the natural history of ductal carcinoma in situ (DCIS) are necessary to accurately model it and estimate overdiagnosis. To improve current estimates of overdiagnosis (0-91%), the purpose of this review was to identify and analyse assumptions made in modelling studies on the natural history of DCIS in women. A systematic review of English full-text articles using PubMed, Embase, and Web of Science was conducted up to February 6, 2023. Eligibility and all assessments were done independently by two reviewers. Risk of bias and quality assessments were performed. Discrepancies were resolved by consensus. Reader agreement was quantified with Cohen's kappa. Data extraction was performed with three forms on study characteristics, model assessment, and tumour progression. Thirty models were distinguished. The most important assumptions regarding the natural history of DCIS were addition of non-progressive DCIS of 20-100%, classification of DCIS into three grades, where high grade DCIS had an increased chance of progression to invasive breast cancer (IBC), and regression possibilities of 1-4%, depending on age and grade. Other identified risk factors of progression of DCIS to IBC were younger age, birth cohort, larger tumour size, and individual risk. To accurately model the natural history of DCIS, aspects to consider are DCIS grades, non-progressive DCIS (9-80%), regression from DCIS to no cancer (below 10%), and use of well-established risk factors for progression probabilities (age). Improved knowledge on key factors to consider when studying DCIS can improve estimates of overdiagnosis and optimization of screening.

Feasibility analysis of magnetic resonance imaging-based radiomics features for preoperative prediction of nuclear grading of ductal carcinoma in situ.

The nuclear grading of ductal carcinoma in situ (DCIS) affects its clinical risk. The aim of this study was to investigate the possibility of predicting the nuclear grading of DCIS, by magnetic resonance imaging (MRI)-based radiomics features. And to develop a nomogram combining radiomics features and MRI semantic features to explore the potential role of MRI radiomic features in the assessment of DCIS nuclear grading. A total of 156 patients (159 lesions) with DCIS and DCIS with microinvasive (DCIS-MI) were enrolled in this retrospective study, with 112 lesions included in the training cohort and 47 lesions included in the validation cohort. Radiomics features were extracted from Dynamic contrast-enhanced MRI (DCE-MRI) phases 1st and 5th. After feature selection, radiomics signature was constructed and radiomics score (Rad-score) was calculated. Multivariate analysis was used to identify MRI semantic features that were significantly associated with DCIS nuclear grading and combined with Rad-score to construct a Nomogram. Receiver operating characteristic curves were used to evaluate the predictive performance of Rad-score and Nomogram, and decision curve analysis (DCA) was used to evaluate the clinical utility. In multivariate analyses of MRI semantic features, larger tumor size and heterogeneous enhancement pattern were significantly associated with high-nuclear grade DCIS (HNG DCIS). In the training cohort, Nomogram had an area under curve (AUC) of 0.879 and Rad-score had an AUC of 0.828. Similarly, in the independent validation cohort, Nomogram had an AUC value of 0.828 and Rad-score had an AUC of 0.772. In both the training and validation cohorts, Nomogram had a significantly higher AUC value than Rad-score (P<0.05). DCA confirmed that Nomogram had a higher net clinical benefit. MRI-based radiomic features can be used as potential biomarkers for assessing nuclear grading of DCIS. The nomogram constructed by radiomic features combined with semantic features is feasible in discriminating non-HNG and HNG DCIS.

Abstract A011: Effectiveness of an online decision support tool in communicating information about treatment options and related risks for ductal carcinoma in situ (DCIS)

Abstract Introduction: Treatment options for women diagnosed with DCIS require careful consideration of the potential risks and benefits. An interactive decision support tool (DST) was developed to provide information about these options, including their potential long-term risk. The DST was implemented through the website www.dcisoptions.org in collaboration with the AFT-25 Comparing an Operation to Monitoring, with or without Endocrine Therapy (COMET), for low-risk DCIS study. Methods: The DST provides personalized prediction of the potential clinical impact of six different treatment options over a 10-year period. Women were asked to select one or more option, and to complete two surveys - one prior to interacting with the DST and one following interaction. Chi-square tests were used to compare the distribution of age group and DCIS grade among women who completed both surveys and those who completed the pre-tool survey only. Mean age was compared using the t-test and median age was compared using the Wilcoxon-Mann-Whitney test. The signed-rank test was used to compare the median age. The cohort that answered both surveys was analyzed for potential differences in response (pre- versus post-tool). The McNemar test was used to compare percentage distributions and the paired t-test was used to compare mean responses for questions using the Likert scale. A signed rank test was used to compare median changes from pre- to post-tool. Statistical significance was defined as P&amp;lt;0.05 in a two-sided test. The primary endpoint of the study was to evaluate the effectiveness of the DST in communicating information about DCIS treatment options and related risk predictions. Results: Data were collected from January 2019 to April 2022 for women (non-COMET participants) who completed the DST. Of those 976 women, 831 (85%) completed the pre-tool survey only and 145 (15%) completed both the pre- and post-tool survey. The mean age was 54.4 (9.8 SD) years. 73% of women had low/intermediate-grade DCIS, while 19% had high-grade DCIS. Among women who submitted both surveys, average time spent completing the DST was 10 minutes. Awareness of the treatment options prior to use of the DST was high (90%), except for active surveillance (85.2%) and bilateral mastectomy (84.3%). Awareness post-tool did not change significantly except for active surveillance (85.2% to 96.5% (p=0.004)). Among women who completed both surveys, the percentage who correctly identified that the chance of dying from DCIS is ‘Very Low’ increased from 60.0% to 73.8% (p&amp;lt;0.0001). The median estimated risk of dying from DCIS in 10 years decreased from 9% to 3% (p&amp;lt;0.0001). A total of 101/132 (76.5%) women that responded to a specific question about the DST found it to be ‘Very Helpful’ or ‘Helpful’ in making a treatment decision for DCIS. A limitation of the study is the lower response rate to the post-tool survey. Conclusion: In this study, we demonstrated that utilization of a DST by women diagnosed with DCIS may enable value-congruent decision making and potentially result in improved patient outcomes. Citation Format: Thomas Lynch, Ann Partridge, E. Shelley Hwang, Alastair Thompson, Elizabeth Frank, Donna Pinto, Deborah Collyar, Desiree Basila, Terry Hyslop, Marc Ryser, Anna Weiss, Anna Rapperport, Rinaa Punglia, Elissa Ozanne. Effectiveness of an online decision support tool in communicating information about treatment options and related risks for ductal carcinoma in situ (DCIS) [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr A011.

Abstract IA021: Challenges of conducting active surveillance for ductal carcinoma in situ (DCIS)

Abstract The COMET (Comparing an Operation to Monitoring, with or without Endocrine Therapy) multicenter Phase III prospective trial randomizes women with low-risk DCIS to either standard of care (surgery +/- radiation therapy) or active surveillance (AS), a management approach in which mammograms and physical exams are used to monitor breast changes and determine when, or if, surgery is needed. It is currently open at 85 Alliance for Clinical Trials in Oncology sites and has accrued 905 patients as of 08/01/22. Initial recruitment challenges related to standardizing pathology eligibility criteria, with re-evaluation regarding the merits of central versus second pathology review, and discordance among pathologists regarding DCIS grade and necrosis. These discussions resulted in evidence-based protocol amendments that subsequently increased accrual. Patients that express a specific treatment preference often decline the arm to which they are randomized (not uncommon in trials of surgery de-escalation). Two consultants were recruited to implement the Quintet Recruitment Intervention, an initiative that utilizes qualitative/quantitative strategies to better understand recruitment in trials with very different treatment arms; acceptance rates in each randomized arm stabilized following this intervention. Patient and provider attitudes also presented a potential barrier to recruitment. Some surgeons lacked equipoise with the concept of AS and possess a “more is more” mentality; others express concern about younger patients undergoing AS; there are also financial implications of conducting AS rather than surgery for some surgeons. Radiologists often provide the initial diagnosis of DCIS to the patient; if the patient is told “DCIS is breast cancer”, they will expect to have surgery. Potential to consider AS may be limited if this preconceived notion about the need for surgery becomes established at the outset. DCIS has been disproportionately influenced by its terminology and classification, which may contribute to women feeling rushed into treatment decisions. Because of the way that DCIS is described to them, women considering AS may feel anxious knowing that the ‘threat’ of invasive breast cancer (IBC) has not been removed. Specific challenges to conducting AS for patients include those with a family history of breast cancer who express a strong desire for surgery. Women who undergo AS may experience ‘anticipatory anxiety’ regarding ongoing surveillance for the disease. Insufficient research exists about how relevant the outcomes of undergoing AS are to women and how patient perception around the potential ‘risk’ of IBC may impact upon their acceptance of AS. Collection of patient-reported outcomes in currently enrolling studies enables the challenges of undergoing AS to be understood from a patient perspective. Changing the treatment paradigm for DCIS requires multidisciplinary collaboration to drive change. However, providing more safe options for patients with low-risk DCIS will significantly reduce treatment-related harms. Citation Format: Thomas Lynch. Challenges of conducting active surveillance for ductal carcinoma in situ (DCIS) [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA021.

Abstract A016: Identification of methylated regions in ductal carcinoma in situ and association with disease progression

Abstract Background: The advent of breast screening has led to a 4-fold increase in the diagnosis of ductal carcinoma in situ (DCIS). Studies following the clinical outcomes of patients show variable progression free survival rates, with only up to 35% of patients progressing to invasive disease without treatment. This highlights the need to find a biomarker to accurately predict which DCIS lesions will recur as invasive tumors. Epigenetics changes are events which occur early in tumorigenesis, this makes DNA methylation a potential biomarker of DCIS progression. However, a lack of DCIS methylation profiling with long term follow-up data exists. This study investigates genome-wide methylation profiles in women with primary DCIS and associates the data with their overall recurrence free survival. Methods: DCIS was macrodissected from 89 formalin-fixed paraffin embedded (FFPE) to extract tumor enriched DNA from patients with DCIS and long term follow up. 39 women had developed an ipsilateral invasive recurrence (classified as cases) and 50 had no evidence of recurrent disease (classified as controls). Genome wide methylation was assessed using the human methylation EPIC BeadChip which, interrogates over 850,000 methylation sites. Data was assessed for quality both at the sample and probe level by the wateRmelon. Further analysis was performed in ChAMP to identify differentially methylated regions (DMR) and by DMRcate packages in R to identify variably methylated regions (VMR). Genes annotated in the most significant VMRs were analysed through Metascape, a web-based tool to perform functional gene set enrichment analysis (GSEA). A cox proportional hazards model was used to calculate the association between the methylation of the VMRs and recurrence free survival. This model was adjusted for DCIS receptor status and grade. Results: 59 samples passed data quality assessment (35 controls and 24 cases). 10 differentially methylated regions were identified. The most significant of which, was a hypomethylated region on chromosome 4, containing CDKL2 (p = 0.001), known to promote the epithelial-mesenchymal transition in breast cancer progression. 5813 VMRs were identified across the genome, (P-value range between 0 and 10-321). 82% of the VMRs aligned to the body of the gene or the surrounding regulatory features. GSEA revealed that VMRs were predominantly involved in pathways involved in cell adhesion (GO:0007156) Assessment of the significant VMRs by COX proportional hazards model showed that a VMR on chromosome 6p was associated with the development of invasive disease after adjusting for oestrogen receptor, human epidermal growth factor 2 status and grade (p=0.001). Conclusions: This preliminary study shows altered sites of methylation could be observed across the genome, in DCIS. The function of the VMRs is currently being investigated to understand how methylation in this region predisposes to invasive recurrence of DCIS. Correlation of methylation status and RNA expression data will be used to understand the biological relevance. Citation Format: Vandna Shah, Maria Roman-Escorza, Karen Clements Clements, Lennart Mulder, Esther H. Lips, Jelle Wesseling, Sarah Pinder, Alastair M. Thompson, Elinor J. Sawyer. Identification of methylated regions in ductal carcinoma in situ and association with disease progression [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr A016.

Differential involvement of germline pathogenic variants in breast cancer genes between DCIS and low-grade invasive cancers

PurposeTo investigate frequency of germline pathogenic variants (PVs) in women with ductal carcinoma in situ (DCIS) and grade 1 invasive breast cancer (G1BC).MethodsWe undertook BRCA1/2 analysis in 311 women with...

Dimorphic cells: a common feature throughout the low nuclear grade breast neoplasia spectrum

Columnar cell lesions (CCLs) are recognized precursor lesions of the low nuclear grade breast neoplasia family. CCLs are cystic enlarged terminal duct lobular units with monotonous (monoclonal) columnar-type luminal cells. CCLs without atypia are regarded as benign and CCLs with atypia as true precursor lesions with clonal molecular changes, a certain progression risk, and an association with more advanced lesions. However, reproducibility of designating atypia in CCL is not optimal, and no objective markers of atypia have been identified, although 16q loss seems to be associated with atypical CCLs. Dimorphic (“pale”) cell populations have been described in low nuclear grade ductal carcinoma in situ (DCIS) but not in CCLs and atypical ductal hyperplasia (ADH). Therefore, we searched for pale cells in CCL (N = 60), ADH (N = 41), and DCIS grade 1 (N = 84). Diagnostic criteria were derived from the WHO, and atypia was designated according to the Schnitt criteria. Pale cells occurred in 0% (0/30), 73% (22/30), 56% (23/41), and 76% (64/84) of CCLs without atypia, CCLs with atypia, ADH, and DCIS grade 1, respectively. Pale cells expressed ERα, E-cadherin and p120 and variably cyclin D1, and lacked expression of CK5 and p63. In conclusion, dimorphic “pale” cells occur throughout the low nuclear grade progression spectrum, increasing in frequency with progression. Interestingly, CCL lesions without atypia do not seem to bear showed pale cells, indicating that the presence of pale cells may serve as a diagnostic morphological feature of atypia in CCLs.

[The value of immunohistochemical expression of Ki-67 and CD34 in differentiating ductal carcinoma in situ from ductal carcinoma in situ-like invasive breast cancer].

Objective: To investigate the expression of Ki-67 and CD34 in the differential diagnosis of ductal carcinoma in situ (DCIS) and DCIS-like invasive breast cancer (DLIBC). Methods: A total of 100 cases of DCIS and 150 cases of DLIBC diagnosed pathologically in Yantai Yuhuangding Hospital from January 2019 to March 2022 were collected. The expression of p63, CK5/6, Ki-67 and CD34 in both groups were detected by immunohistochemical (IHC) staining and evaluated. Results: The 100 cases of DCIS included 11 cases of low-grade DCIS, 28 cases of intermediate-grade DCIS and 61 cases of high-grade DCIS. IHC staining of p63 and CK5/6 showed the myoepithelial cells around cancerous duct were complete or partial absence. Ki-67 expression showed two patterns: high expression in the basal layers and scattered expression within the tumor. Most cases showed mainly high basal expression (77/100, 77%), and the proportion of this pattern was significantly different between low grade and high grade DCIS (P<0.05). All cases showed complete CD34 expression surrounding the cancerous duct with different proportion (vascular necklace) suggested small vessels proliferation. The 150 cases of DLIBC included 142 cases of invasive ductal carcinoma (IDC) (three cases of basal-like breast cancer was included), two cases of secretory carcinoma, three cases of solid papillary carcinoma, two cases of adenoid cystic carcinoma and one case of acinar cell carcinoma. Among 142 cases of IDC, 13 cases were grade Ⅰ, 77 were grade Ⅱ and 52 were grade Ⅲ. IHC staining of p63 showed complete absence of myoepithelium. CK5/6 was negative in most cases and only positively expressed within the tumor in 3 cases of basal-like breast cancer. Ki-67 indicated a scattered expression pattern within the tumor. In most cases, CD34 immunostaining showed scattered positive blood vessels within the tumor while only two cases showed incomplete expression of CD34 around the tumor (2/150, 1.3%). The different expression patterns of Ki-67 and CD34 in DCIS and DLIBC was statistically significant (P<0.05). Conclusions: The different expression patterns of Ki-67 and CD34 are helpful to distinguish DLIBC from DCIS. The appearance of "vascular necklace" with CD34 and the high expression of Ki-67 around the cancerous duct highly support the diagnosis of DCIS, and the scattered expression pattern of CD34 supports DLIBC.

Diffusion-weighted Breast MRI in Prediction of Upstaging in Women with Biopsy-proven Ductal Carcinoma in Situ.

Background Accurate preoperative prediction of upstaging in women with biopsy-proven ductal carcinoma in situ (DCIS) is important for surgical planning, but published models using predictive MRI features remain lacking. Purpose To develop and validate a predictive model based on preoperative breast MRI to predict upstaging in women with biopsy-proven DCIS and to select high-risk women who may benefit from sentinel lymph node biopsy at initial surgery. Materials and methods Consecutive women with biopsy-proven DCIS who underwent preoperative 3.0-T breast MRI including dynamic contrast-enhanced (DCE) MRI and diffusion-weighted imaging (DWI) and who underwent surgery between June 2019 and March 2020 were retrospectively identified (development set) from an academic medical center. The apparent diffusion coefficients of lesions from DWI, lesion size and morphologic features on DCE MRI scans, mammographic findings, age, symptoms, biopsy method, and DCIS grade at biopsy were collected. The presence of invasive cancer and axillary metastases was determined with surgical pathology. A predictive model for upstaging was developed by using multivariable logistic regression and validated in a subsequent prospective internal validation set recruited between July 2020 and April 2021. Results Fifty-seven (41%) of 140 women (mean age, 53 years ± 11 [SD]) in the development set and 43 (41%) of 105 women (mean age, 53 years ± 10) in the validation set were upstaged after surgery. The predictive model combining DWI and clinical-pathologic factors showed the areas under the receiver operating characteristic curve at 0.87 (95% CI: 0.80, 0.92) in the development set and 0.76 (95% CI: 0.67, 0.84) in the validation set. The predicted probability of invasive cancer showed good interobserver agreement (intraclass correlation coefficient, 0.79); the positive predictive value was 85% (28 of 33), and the negative predictive value was 92% (22 of 24). Conclusion A predictive model based on diffusion-weighted breast MRI identified women at high risk of upstaging. © RSNA, 2022 Online supplemental material is available for this article See also the editorial by Baltzer in this issue. An earlier incorrect version appeared online. This article was corrected on July 7, 2022.

A prospective decision impact study to evaluate the utility of the Oncotype DX Breast DCIS score assay in selecting patients with ductal carcinoma in situ (DCIS) following breast conservation surgery (BCS) for radiotherapy.

e12571 Background: There is increasing reliance on data provided by genomic risk assessment assays to guide therapeutic decisions. The objective of this prospective study was to assess the impact of the Oncotype DX Breast DCIS Score assay on radiation treatment recommendations in patients with DCIS undergoing BCS. Methods: This decision impact study is a prospectively enrolled observational study of newly diagnosed patients (n = 135) following BCS for removal of DCIS of all grades 30mm or less with clear margins (i.e. 2 mm or normal re-excised margins). Only patients who were candidates to receive radiation therapy were considered. Fifteen patients withdrew from the study or had insufficient volume of DCIS for assay analysis. Radiation Oncologists were blinded to the Oncotype DX Breast DCIS Score assay prior to recording their recommendation for radiotherapy or not. IRB approval was granted following review of study protocol and informed consent was obtained from all patients. Results: Among 120 patients tested, the Oncotype DX Breast DCIS Score assay determined that 58/120 (48.3%) of patients had a low score (LS) (0-38), 30/120 (25%) had an intermediate score (IS) (39-54) and 32/120 (26.7%) had a high score (HS) (&gt;55). The Oncotype DX Breast DCIS Score assay concurred with the Radiation Oncologists recommendation to proceed with radiation treatment in 96.7% of patients (i.e. 60/62 patients with an IS or HS). The Oncotype DX Breast DCIS Score assay altered treatment decisions in 12.5% (4/32) of patients with a HS and in 7.1% (2/28) patient with an IS. In patients where the Oncotype DX Breast DCIS Score assay altered treatment recommendation all had a low volume (i.e. less than 10mm) of high/intermediate grade DCIS with an IS or HS. Conclusions: This study demonstrates that Oncotype DX Breast DCIS Score assay accurately supports the selection of patients with DCIS for radiation treatment and equally can be helpful in selecting a subgroup of patients with small volumes of intermediate/high grade DCIS who can potentially avoid radiotherapy.