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Background:Better tools are needed to estimate the risk of local recurrence (LR; DCIS or invasive) after breast-conserving surgery (BCS) for pts with DCIS in order to inform treatment decisions. Traditional clinico-pathologic (CP) factors, e.g., age and tumor size, provide an average LR risk derived from clinical trials and population studies. The Oncotype DX 12-gene DCIS Score assay has been validated to provide individual 10 yr LR risk estimates (Solin JNCI 2013; Rakovitch BCRT 2015). Previously we reported the impact of the DCIS Score result on radiotherapy (RT) recommendations including the pre-assay LR risk and RT recommendation and the change in RT recommendation from pre- to post-assay (Manders Ann Surg Oncol 2016).Recently a patient specific meta-analysis (MA) combined data from E5194 and Ontario DCIS Cohort (ODC) adjusting for pertinent clinico-pathologic factors to provide refined prediction estimates of LR risk after BCS alone (Rakovitch ASCO 2017). Herein we applied these risk estimates integrating DS, tumor size and patient age with adjustment for diagnosis in the year 2000 or later to refine estimates of LR in DCIS patients from the Manders et al study. Methods: 13 U.S. sites enrolled pts with DCIS treated with BCS alone from 3/2014 to 5/2015. Pts with LCIS but no DCIS, invasive BC, or planned mastectomy were excluded. Data were prospectively collected on CP factors, physician estimates of LR risk, and DCIS Score. Refined estimates of 10-yr risk of LR are presented by DCIS Score result category (0-38; 39-54; 55-100), age group (≥50 vs 1-2.5; >2.5 cm). Results: Of the 127 pts enrolled, median age was 60 yr,79.5% were postmenopausal. Median size was 8mm & 39% were ≤5mm. Median margin width was 3.0mm. ER and PR by IHC were positive in 89% and 78% of pts, respectively. For patients ≥50 yr with tumors ≤1 cm and low risk DS, the 10-yr LR risk ranges from 5.3-10.0%. A high DS result is associated with a higher 10-yr median predicted risk of LR in all subsets (table 1). The DCIS Score integrated with tumor size and patient age and the adjustment for diagnosis in 2000 or later provided risk estimates that are often lower than those provided by the DCIS Score alone without adjustment for diagnostic year. Using DS alone the percentage of patients with risk of LR Conclusions: Integration of the DCIS Score assay, that provides individual risk estimates of LR, with patient age and DCIS tumor size and adjusting for diagnosis in 2000 or later, provides refined estimates of 10-yr LR risk after BCS alone for DCIS. This integration enhances prognostic LR risk estimates and frequently provides lower risk estimates with which to guide individualized treatment decisions. Distribution of 10-year risk of local recurrence using DCIS Score (DS), tumor size, and age, adjusting for diagnosis in 2000 or later. Low DS (1-2.5≥50249.5 (7.3-12.6)914.2 (12.9-15.6)519.6 (16.5-20.4) < 50216.4 (16.1-16.7)220.4 (19.8-21.1)122.2 (22.2-22.2)>2.5≥50515.7 (14.9-23.7)0 138.4 (38.4-38.4) Citation Format: Manders JB, Solin LJ, Leonard CE, Mamounas EP, Lu R, Turner M, Baehner FL, White J. Refined estimates of local recurrence risk in a clinical utility study: Integrating the DCIS score, patient age and DCIS tumor size [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-15-09.

Most newly diagnosed ductal carcinoma in situ (DCIS) is treated with breast-conserving surgery (BCS) ± radiation therapy (RT). A key challenge is deciding whether or not to include RT with BCS. This decision is often determined by the degree of risk associated with disease recurrence. However, methods for risk assessment have not kept pace with diagnostic advances. The DCIS Score is an independent predictor and quantifier of individualized recurrence risk in patients with DCIS. Although the test is the only available genomic classifier for DCIS, the degree of adoption is varied, and it has not yet been fully accepted as standard practice. Recognizing the importance of individualizing recurrence assessment in patients with DCIS, the authors convened to review relevant clinical data, share best practices, and establish recommendations regarding how the assay should be incorporated into the decision-making process. Based on their clinical experiences, the authors concluded that effective integration of the DCIS Score should involve shared decision-making between surgeons and other specialties (radiation oncologists, pathologists, patient navigators, and physician assistants), with the patient's preference being a primary consideration. This manuscript aims to provide easy-to-use, clear-cut, and practical guidance to help physicians utilize the DCIS Score to improve risk assessment and inform treatment decisions for their patients with DCIS, including how to understand, run, interpret, and communicate the actionable results to patients.

Background: In the management of DCIS clinicians and patients (pts) must choose between the various options for breast conservation treatment based on an assessment of local recurrence (LR) risk. Traditional clinicopathologic (CP) factors such as age, size, grade, margin width or comedo necrosis, provide an average LR risk derived from clinical trials and population studies. The Oncotype DX® 12-gene assay for DCIS gives individual 10-yr LR risk estimates and has now been validated in two studies in a total of 893 pts. We report the 2nd study assessing the impact of the DCIS Score result on XRT recommendations. In addition, surveys assessing pt and physician confidence will provide insight into the overall clinical utility of the DCIS Score result. Baseline characteristics including the pre-assay LR risk and XRT recommendation are described here; final results on change in XRT recommendation from pre- to post-assay and distribution of the score across the CP factors will be presented. Methods: 13 U.S. sites enrolled pts with DCIS from 3/2014-5/2015. Pts with LCIS but no DCIS, invasive BC, or planned mastectomy were excluded. Data were prospectively collected on CP factors, physician estimates of LR risk, DCIS score, and pre/post XRT recommendation. Each pt had a surgeon and radiation oncologist complete study surveys. Pt surveys were also administered pre/post assay for decision conflict and the STAIT anxiety survey. The LR risk estimates and XRT recommendations were analyzed for all physicians as well as by specialty. Descriptive statistics summarized study variables. 95% Clopper-Pearson Exact CIs were calculated for percent change in XRT recommendation. McNemar's test was used to determine if the proportion of pts had a significant change in XRT recommendation post assay. Paired t-tests were used to compare physician estimates of recurrence risk pre/post assay. Results: Of the 121 pts enrolled, median age was 61y (34-83) and 80.2% were postmenopausal. Median size was 8mm and 40% were < 5mm; 22.3% were grade 1, 51.2% grade 2, and 26.4% grade 3. Comedo necrosis was noted in 55.4% and 19% had multiple foci. Median margin width was 3mm and 47.1% had margins 1-3mm. ER and PR by IHC were positive in 88.4% and 75.2% of pts. Among the 242 MD risk assessments, mean 10-yr LR risk was 14.8% (range 4-50%) for any LR; 14.2% for surgeons and 15.3% for radiation oncologists. The pre-assay XRT recommendation was 70.2%; 68.6% for surgeons and 71.9% for radiation oncologists. Conclusions: The role of new molecular tools such as the DCIS Score assay that provide individual risk estimates for LR on treatment decisions is evolving. The DCIS pts enrolled in the study reveal inclusion of baseline features like higher nuclear grade (26%), comedo necrosis (55%) and margin width of 1-3mm (47%) that have historically been associated with XRT use. This represents a continued broadening of the assay use from the predominantly lower risk DCIS cohort in the 1st validation study (E5194). The impact on XRT decisions is critical to establishing the clinical utility of the assay. The decision impact analysis, differences in use of the assay among surgeons and radiation oncologists and the impact on overall confidence with the treatment decision will be presented. Citation Format: Manders JB, Kuerer HM, Smith BD, McCluskey C, Farrar WB, Frazier TG, Li L, Leonard CE, Carter DL, Chawla S, Medeiros LE, Guenther JM, Castellini LE, Buchholz DJ, Mamounas EP, Wapnir IL, Horst KC, Chagpar A, Evans SB, Riker AI, Vali FS, Solin LJ, Jablon L, Recht A, Sharma R, Lu R, Sing AP, Hwang ES, White J. The 12-gene DCIS score assay: Impact on radiation treatment (XRT) recommendations and clinical utility. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-17-03.

Twenty percent of breast cancers are ductal carcinoma in situ (DCIS), with 15-60% having a local recurrence (LR) after surgery. Radiotherapy reduces LR by 50% but has not impacted survival. The validated Oncotype DX(®) 12-gene assay (DCIS Score) provides individualized 10-year LR estimates. This is the first study to assess whether DCIS Score impacts physicians' recommendations for radiation.Ten sites enrolled women (9/2012-2/2014) with DCIS eligible for breast-conserving therapy, excluding patients with invasive carcinoma and planned mastectomy. Prospective data collected included clinicopathologic factors, DCIS Score assay, and treatment recommendation before and after the assay result was known.In 115 patients (median age: 61 years; 74.8% postmenopausal), median DCIS size was 8 mm; 20% were nuclear grade 1, 46.1% grade 2; 64.4% reported necrosis. 86.1% were ER+, 79.1% PR+ (immunohistochemistry assay). Median DCIS Score: 29 (range: 0-85). Pre-assay, 73% (95%CI: 64.0-80.9%) had radiotherapy recommendations vs. 59.1% (95%CI: 49.6-68.2%) post-assay (P= 0.008). Physicians rated DCIS Score as the most impactful factor in planning treatment.The radiotherapy recommendation changed from pre-assay to post-assay 31.3% (95%CI: 23.0-40.6%) of the time--a clinically significant change. This study supports the clinical utility of the DCIS Score and indicates that the test provides additional, individualized information on LR risk.

11050 Background: About 20% of breast cancers (BC) are DCIS. Local recurrence (LR) rates with surgery alone are 15-60%; about 50% are invasive. Radiation (XRT) reduces LR by 50% but has not impacte...

30 Background: The utilization of the 21-gene Recurrence Score (Oncotype DX) in community settings is now well established for ER+, node negative (N-) pts with ESBC. The utility of the Recurrence Score result is to guide treatment decisions and spare exposure to chemotherapy (CT) in pts that have little likelihood of benefitting. To better understand physician behavior as it relates to OncotypeDX testing, we examined the characteristics of pts tested versus not tested, the Recurrence Score distribution and treatment patterns in approximately 160 pts with ESBC seen in 2010. In addition, provider utilization and treatment patterns were also assessed. Methods: Using data from 2010, the number of pts who were eligible to undergo OncotypeDX testing was compared to the number of pts who underwent testing. Pts were considered eligible for testing if they had node-negative, ER+, HER2-negative ESBC. We determined the number of pts with a Recurrence Score value in the low (RS

Objective The aim of this study was to determine the impact of the results of the 12-gene DCIS Score assay on (i) radiotherapy recommendations for patients with pure ductal carcinoma in situ (DCIS) following breast-conserving surgery (BCS), and (ii) patient decisional conflict and state anxiety. Methods Thirteen sites across the US enrolled patients (March 2014–August 2015) with pure DCIS undergoing BCS. Prospectively collected data included clinicopathologic factors, physician estimates of local recurrence risk, DCIS Score results, and pre-/post-assay radiotherapy recommendations for each patient made by a surgeon and a radiation oncologist. Patients completed pre-/post-assay decisional conflict scale and state-trait anxiety inventory instruments. Results The analysis cohort included 127 patients: median age 60 years, 80 % postmenopausal, median size 8 mm (39 % ≤5 mm), 70 % grade 1/2, 88 % estrogen receptor-positive, 75 % progesterone receptor-positive, 54 % with comedo necrosis, and 18 % multifocal. Sixty-six percent of patients had low DCIS Score results, 20 % had intermediate DCIS Score results, and 14 % had high DCIS Score results; the median result was 21 (range 0–84). Pre-assay, surgeons and radiation oncologists recommended radiotherapy for 70.9 and 72.4 % of patients, respectively. Post-assay, 26.4 % of overall recommendations changed, including 30.7 and 22.0 % of recommendations by surgeons and radiation oncologists, respectively. Among patients with confirmed completed questionnaires (n = 32), decision conflict (p = 0.004) and state anxiety (p = 0.042) decreased significantly from pre- to post-assay. Conclusions Individualized risk estimates from the DCIS Score assay provide valuable information to physicians and patients. Post-assay, in response to DCIS Score results, surgeons changed treatment recommendations more often than radiation oncologists. Further investigation is needed to better understand how such treatment changes may affect clinical outcomes. Electronic supplementary material The online version of this article (doi:10.1245/s10434-016-5583-7) contains supplementary material, which is available to authorized users.