Risk Of Ipsilateral Breast Event Research Articles

Abstract GS02-08: Five-year outcomes of the IDEA trial of endocrine therapy without radiotherapy after breast-conserving surgery for postmenopausal patients age 50-69 with genomically-selected favorable Stage I breast cancer

Abstract Background: Multiple studies have shown a low risk of ipsilateral breast events (IBE) or other recurrences for selected patients age 65-70 or older with Stage I breast cancers treated with breast conserving surgery (BCS) and endocrine therapy (ET) without adjuvant radiotherapy (RT). We designed a prospective single-arm trial, IDEA (Individualized Decisions for Endocrine therapy Alone), to see if younger postmenopausal patients could also be successfully treated without RT, adding a genomic assay to classic selection factors. Methods: Postmenopausal patients aged 50-69 with pT1N0 unifocal invasive breast cancer with margins 2 mm or wider after BCS whose tumors were ER+, PR+, and Her2- with Oncotype DX 21-gene recurrence score (RS) 18 or lower were eligible to avoid RT if they consented to take at least 5 years of ET and surveillance on study. The primary endpoint was the rate of breast cancer recurrence at 5 years of follow-up after BCS. A valid 5–year assessment was defined as a clinical assessment within 4 months prior to the 5-year anniversary or later. Follow-up time was calculated from the date of BCS until first recurrence [ipsilateral breast events (IBE) or regional or distant failures] or to last clinical follow-up. The time-to-event endpoint was calculated using the product-limit method of Kaplan and Meier measured from the date of BCS. Results: 200 eligible patients were enrolled from 13 US institutions between June 2015 and October 2018. Median age was 63 years (IQR 58-66); mean RS was 11.2 (SD 4.8). Tumors were grade 1 in 85 patients, grade 2 in 109, and grade 3 in 6. Mean tumor size was 10 mm (SD 4.6). Lymphovascular invasion was present in 16 tumors and an extensive intraductal component in 11. Median follow-up time was 5.21 years (IQR 5.01-5.97); 8 of 14 patients with less than 56 months of follow-up were lost to follow-up. Overall and breast cancer-specific survival rates at 5 years were both 100%; 2 deaths occurred later than 5 years. The 5-year freedom from recurrence was 99% (95% CI, 96%-100%). One of the two events occurring by 5 years was an isolated axillary recurrence at 21 months treated with axillary dissection and breast and regional nodal irradiation. The other was an IBE at 49 months, treated with repeat BCS. Both these patients had been compliant with ET. Six additional patients recurred later than 5 years after BCS (5 IBEs, 1 IBE plus regional recurrence). Crude rates of IBE for the entire follow-up period for patients aged 50-59 and 60-69 were 3.3% (2/60) and 3.6% (5/140), respectively; crude rates of overall relapse were 5.0% (3/60) and 3.6% (5/140). Conclusions: This multicenter trial of ET without RT following BCS achieved a very low risk of relapse for postmenopausal patients with Stage I cancers using a genomic assay in combination with classic clinical and biologic features for treatment selection, including for patients younger than age 60. IDEA demonstrates a 5-year probability of recurrence consistent with or lower than the 4% risk estimated a priori, and the patients accrued were younger when compared to prior prospective trials (e.g., PRIME II, minimum age 65; CALGB 9343, minimum age 70; LUMINA, median age 67). The results of ongoing NRG BR007 trial, which randomly allocates women meeting these eligibility criteria to receive RT or not, and similar randomized and single-arm studies will help determine whether the option of avoiding initial RT can be offered to a broader group of women than current guidelines recommend. Long-term follow-up beyond the 5-year required period of ET will be important to determine if the risk of recurrence increases, particularly after discontinuation of ET. Citation Format: Reshma Jagsi, Kent Griffith, Eleanor Harris, Jean Wright, Abram Recht, Alphonse Taghian, Lucille Lee, Meena Moran, William Small, Candice Johnstone, Asal Rahimi, Gary Freedman, Mahvish Muzaffar, Bruce Haffty, Kathleen Horst, Simon Powell, Jody Sharp, Michael Sabel, Anne Schott, Mahmoud El-Tamer. Five-year outcomes of the IDEA trial of endocrine therapy without radiotherapy after breast-conserving surgery for postmenopausal patients age 50-69 with genomically-selected favorable Stage I breast cancer [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 GS02-08.

Lumpectomy without radiation for ductal carcinoma in situ of the breast: 20-year results from the ECOG-ACRIN E5194 study

We report the 20-year rate of ipsilateral breast event (IBE) for patients with ductal carcinoma in situ (DCIS) treated with lumpectomy without radiation on a non-randomized prospective clinical trial. Patients were enrolled in cohort 1: low- or intermediate-grade DCIS, size ≤ 2.5 cm (n = 561); or cohort 2: high-grade DCIS, size ≤ 1 cm (n = 104). The Kaplan–Meier method was used to estimate time-to-event distributions. Cox proportional hazard methods were used to estimate hazard ratios (HRs) and tests for significance for event times. 561 patients were enrolled in cohort 1 and 104 in cohort 2. After central pathology review, 26% in cohort 1 were recategorized as high-grade and 26% in cohort 2 as low- or intermediate-grade. Mean DCIS size was similar at 7.5 mm in cohort 1 and 7.8 mm in cohort 2. Surgical margin was ≥3 mm in 96% of patients, and about 30% received tamoxifen. Median follow-up was 19.2 years. There were 104 IBEs, of which 54 (52%) were invasive. The IBE and invasive IBE rates increased in both cohorts up to 15 years, then plateaued. The 20-year IBE rates were 17.8% for cohort 1 and 28.7% for cohort 2 (p = 0.005), respectively. Invasive IBE occurred in 9.8% and 15.1% (p = 0.09), respectively. On multivariable analysis, IBE risk increased with size and was higher in cohort 2, but grade and margin width were not significantly associated with IBE. For patients with DCIS treated with excision without radiation, the rate of IBE increased with size and assigned cohort mostly in the first 15 years.

Omission of Radiotherapy After Breast-Conserving Surgery for Women With Breast Cancer With Low Clinical and Genomic Risk: 5-Year Outcomes of IDEA.

Multiple studies have shown a low risk of ipsilateral breast events (IBEs) or other recurrences for selected patients age 65-70 years or older with stage I breast cancers treated with breast-conserving surgery (BCS) and endocrine therapy (ET) without adjuvant radiotherapy. We sought to evaluate whether younger postmenopausal patients could also be successfully treated without radiation therapy, adding a genomic assay to classic selection factors. Postmenopausal patients age 50-69 years with pT1N0 unifocal invasive breast cancer with margins ≥2 mm after BCS whose tumors were estrogen receptor-positive, progesterone receptor-positive, and human epidermal growth factor receptor 2-negative with Oncotype DX 21-gene recurrence score ≤18 were prospectively enrolled in a single-arm trial of radiotherapy omission if they consented to take at least 5 years of ET. The primary end point was the rate of locoregional recurrence 5 years after BCS. Between June 2015 and October 2018, 200 eligible patients were enrolled. Among the 186 patients with clinical follow-up of at least 56 months, overall and breast cancer-specific survival rates at 5 years were both 100%. The 5-year freedom from any recurrence was 99% (95% CI, 96 to 100). Crude rates of IBEs for the entire follow-up period for patients age 50-59 years and age 60-69 years were 3.3% (2/60) and 3.6% (5/140), respectively; crude rates of overall recurrence were 5.0% (3/60) and 3.6% (5/140), respectively. This trial achieved a very low risk of recurrence using a genomic assay in combination with classic clinical and biologic features for treatment selection, including postmenopausal patients younger than 60 years. Long-term follow-up of this trial and others will help determine whether the option of avoiding initial radiotherapy can be offered to a broader group of women than current guidelines recommend.

Predicting ipsilateral recurrence in women treated for ductal carcinoma in situ using machine learning and multivariable logistic regression models

PurposeTo develop machine learning (ML) and multivariable regression models to predict ipsilateral breast event (IBE) risk after ductal carcinoma in situ (DCIS) treatment. MethodsA retrospective investigation was conducted of patients diagnosed with DCIS from 2007 to 2014 who were followed for a minimum of five years after treatment. Data about each patient were extracted from the medical records. Two ML models (penalized logistic regression and random forest) and a multivariable logistic regression model were developed to evaluate recurrence-related variables. Results650 women (mean age 56 years, range 27–87 years) underwent treatment for DCIS and were followed for at least five years after treatment (mean 8.0 years). 5.5% (n = 36) experienced an IBE. With multivariable analysis, the variables associated with higher IBE risk were younger age (adjusted odds ratio [aOR] 0.96, p = 0.02), dense breasts at mammography (aOR 3.02, p = 0.02), and < 5 years of endocrine therapy (aOR 4.48, p = 0.02). The multivariable regression model to predict IBE risk achieved an area under the receiver operating characteristic curve (AUC) of 0.75 (95% CI 0.67–0.84). The penalized logistic regression and random forest models achieved mean AUCs of 0.52 (95% CI 0.42–0.61) and 0.54 (95% CI 0.43–0.65), respectively. ConclusionVariables associated with higher IBE risk after DCIS treatment include younger age, dense breasts, and <5 years of adjuvant endocrine therapy. The multivariable logistic regression model attained the highest AUC (0.75), suggesting that regression models have a critical role in risk prediction for patients with DCIS.

Abstract P1-22-02: Subsequent risk of ipsilateral breast events in a multinational DCIS cohort of 48.619 patients: A meta-analysis within the PRECISION consortium

Abstract Background: The PRECISION (PREvent ductal Carcinoma In Situ Invasive Overtreatment Now) CRUK Grand Challenge project focusses on discriminating hazardous from indolent ductal carcinoma in situ (DCIS). Aim of these analyses is to identify factors associated with a lower or higher risk of developing invasive breast cancer after an initial DCIS diagnosis. Knowledge of these factors is crucial in our quest to reducing overtreatment for women with DCIS. Many clinicopathological features are hypothesized to be important factors affecting the risk of a subsequent breast lesion. Most studies performed so far are from trial or single country studies, we now present an integrated analysis of four different cohorts from three countries.Methods: Four cohorts from the three countries participating in PRECISION were identified. A population based cohort from the Netherlands cancer registry (Dutch cohort); a population based, prospective, screening cohort from the United Kingdom (Sloane cohort); a single center cohort from MD Anderson Cancer Center (MDACC) and a subset of DCIS patients abstracted from a population based National Cancer Database Special Study cohort (NCDB subset) in the United States. Patient-level data from these cohorts were combined for this analysis. Subsequent ipsilateral invasive breast cancer (iIBC) and subsequent ipsilateral DCIS (iDCIS) were assessed at five and ten years by Kaplan Meier analysis. The cumulative incidence of iIBC was assessed in three treatment groups: breast conserving surgery only (BCS), breast conserving surgery with radiotherapy (BCS+RT) and mastectomy (MST). Cumulative incidence of iDCIS was assessed in patients receiving BCS or BCS+RT. Additionally, cumulative incidences were calculated for iIBC and IDCIS in patients who received endocrine treatment (ET) after BCS or BCS+RT versus patients who did not receive ET. All cumulative incidences were calculated with death as competing risk. Results: The joint PRECISION cohort consisted of 48,619 patients, diagnosed between 1999 and 2017. Median follow-up was 7.4 years (0.6-17.9). In preliminary analyses, Kaplan Meier curves showed broadly similar risks in iIBC and iDCIS between the four different cohorts. The cumulative incidence of iIBC was 1.6% at five years and 3.5% at 10 years. Five-year cumulative incidence of iIBC was highest in patients receiving BCS (3.4%) compared with patients receiving BCS+RT or MST (1.3%). The cumulative incidence of iDCIS was 1.7% at 5 years and 2.4% at 10 years. Five-year cumulative incidence of iDCIS was higher in patients receiving BCS (3.5%) compared to patients receiving BCS+RT (1.9%). In univariate analyses, the effect of ET on cumulative incidence of both iIBC and iDCIS was modest, especially with respect to radiotherapy. Conclusion: Overall, 5- and 10-year incidence of an ipsilateral in situ or invasive breast lesion was low and similar between the four different cohorts. The incidence of iIBC and iDCIS was higher in patients receiving BCS, compared to women receiving BCS+RT or MST. Table 1.Cohort and patient characteristicsDutch Cohort Sloane MDACCNCDB subsetTotal CohortN=18,995N=8,425N=1,820N=19,379N=48,619Cohort descriptionProspectiveNoYesNoNoPopulation basedYesYesNo, single centerYesScreening and non-screeningYesScreening onlyYesYesMean (min - max)Mean (min - max)Mean (min - max)Mean (min-max)Mean (min-max)Age diagnosis DCIS58.3 (21-94)59.8 (46-88)55.6 (20-90)59.7 (20-98)59.0 (20-98)Year of diagnosis (range)1999-20152003-20121999-20172007-20151999-2017Follow-up in years10.4 (0.5-21.1)5.3 (0.5-9.7)8.7 (0.25-17.8)5.8 (0.5-10.7)7.6 (0.25-2.1)N (%)N (%)N (%)N (%)N (%)GradeGrade 12,844 (15.0)784 (9.3)141 (7.8)3,158 (16.3)6,927 (14.3)Grade 25,952 (31.3)2,328 (27.6)737 (40.5)6,844 (35.3)15,861 (32.6)Grade 38,944 (47.1)5,305 (62.9)933 (51.3)7,848 (40.5)23,030 (47.3)Unknown grade1,255 (6.6)8 (0.1)9 (0.5)1,529 (7.9)2,801 (5.8)Type of surgeryBreast conserving surgery (BCS)11,790 (62.1)5,830 (69.2)1,031 (56.7)14,504 (74.8)33,155 (68.2)Mastectomy (MST)7,205 (37.9)2,595 (30.8)789 (43.4)4,875 (25.2)15,464 (31.8)Adjuvant treatmentRadiotherapy (RT)9,650 (50.8)3,418 (40.6)762 (41.9)10,620 (54.8)24,450 (50.3)Endocrine treatmentNA1,151 (13.6)999 (54.9)8,849 (45.7)10,999 (37.0)5 years Cumulative IncidencesiIBC1.4%2.3%1.6%1.7%1.6%iDCIS1.5%2.0%1.6%1.7%1.7%Vital statusAlive16,472 (86.7)8,147 (96.7)1,668 (91.7)18,161 (93.7)44,448 (91.4)Deceased2,523 (13.3)278 (3.3)152 (8.4)1,218 (6.3)4,171 (8.6)This work was supported by Cancer Research UK and by KWF Dutch Cancer Society (ref.C38317/A24043) Citation Format: Renée SJM Schmitz, Sandra W van den Belt-Dusebout, Chiara Cresta, Yat-Hee Liu, Michael Schaapveld, Karen Clements, Jasmine Timbres, Danalyn T Byng, Marc D Ryser, Yi Ren, Thomas Lynch, Terry Hyslop, Brian Menegaz, Deborah Collyar, Shelley Hwang, Alastair Thompson, Elinor Sawyer, Jelle Wesseling, Esther H Lips, Marjanka K Schmidt, Grand Challenge PRECISION consortium. Subsequent risk of ipsilateral breast events in a multinational DCIS cohort of 48.619 patients: A meta-analysis within the PRECISION consortium [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-22-02.

Abstract P3-18-01: Assessmentof DCISionRT for guiding radiotherapy of DCIS in Sweden

Abstract Background: Radiotherapy (RT) after breast conserving surgery (BCS) for ductal carcinoma in situ (DCIS) reduces the relative ipsilateral breast event (IBE) risk by 50%. The DCISionRT® test estimates IBE risk in DCIS women treated with BCS, and RT benefit. The test has been validated in five cohorts, including the SweDCIS randomized trial. Swedish national guidelines define low-risk DCIS using clinicopathology criteria. Methods: We determined the number of women irradiated per IBE prevented and treatment-costs based on 10-year outcomes from the SweDCIS trial. Four strategies were compared: no RT (Strategy 1); RT for all (Strategy 2), RT for DCISionRT Elevated Risk only (Strategy 3); Swedish DCIS Guidelines, omit RT for low-risk (Strategy 4). In SweDCIS, women were randomised to RT or not after BCS, 1988-2000 (n=1046). Data for DCISionRT biomarkers (PR, HER2, Ki67, FOXA1, p16/INK4A, SIAH2, COX2) and clinical factors (age, tumor size, margin, palpability) were available for 504 women with negative margins. A decision score (DS, 0-10) was reported. The associations between Low (DS≤3) and Elevated Risk (DS&amp;gt;3) groups, and 10-year recurrences, and RT effect were assessed. Algorithms for mean treatment costs depending on adjuvant RT and type of recurrence, including secondary surgery, reconstruction, RT, and chemotherapy were based on data from 74 women with recurrence (41 invasive/33 in situ). Costs were based on diagnostic related grouping (DRG) in Sweden, 2020 and transformed to US dollar($). Results: In the SweDCIS validation of DCISionRT, the test divided women into Elevated (52%) and Low Risk (48%) groups. In the Elevated Risk group, RT decreased 10-year relative total and invasive recurrence rates, HR 0.32 (95%CI 0.17-0.58) and 0.24 (0.08-0.74), respectively with absolute decrease of 15.5% (5.9-25.0%) and 9.3% (2.0-16.5%). In the Low Risk group, the relative RT benefit was lower, HR 0.53 (0.28-1.02) and 0.84 (0.30-2.31), with decrease of 5.7% (-0.8-12.2%) and 1.2% (-5.7-8.2%). Invasive and in situ recurrences had an average treatment cost of $21,228 and $19,777, respectively. Treatment of recurrences after initial RT was $983 less expensive. RT-cost was $4,899. Strategy 1: For every 1000 women, 186 develop an IBE within 10-years after BCS without RT, with a treatment-cost in Sweden of $3,752,099. Strategy 2: Treating all women with RT prevents 108 IBE with treatment-costs of $6,467,113. Strategy 3: Treating women at DS Elevated Risk with RT prevents 81 IBE and 480 women are spared RT, with treatment-costs of $4,681,394. The cost of the test is not included. Strategy 4: Using Swedish Guidelines, prevents 100 recurrences and 870 receives RT with treatment-costs of $5,998,002. Compared to Strategy 1, Strategies 2, 3 and 4 decrease IBEs with increased treatment-costs. Treatment-costs increased $25,139/IBE prevented by Strategy 2, $11,473/IBE prevented by Strategy 3, and $26,115/IBE prevented by Strategy 4. The number of women irradiated per IBE prevented were 9.3, 6.4, and 10.1 for strategies 2, 3 and 4, respectively, relative to Strategy 1. Conclusion Strategy 1 (to omit RT) had the lowest treatment-costs and the highest number of recurrences. Strategy 3, using DCISionRT had the lowest number irradiated per IBE prevented at the lowest treatment-cost per IBE prevented. Table 1.DCIS BCS +/-RTRT%Recurrences per 1000 womenCost including RT and treatment of recurrence per 1000BCS RT(-)0%186$3,752,099BCS RT(+)100%78$6,467,113DCISionRT52%105$4,681,394Swedish Guidelines*87%86$5,998,002*Low-risk criteria from modified Swedish national guidelines NG 1–2, &amp;lt;1.5 cm, negative margin, and &amp;lt;52 years (mean age for menopause) Citation Format: Fredrik Wärrnberg, Charlotta Wadsten, Andrea Karakatsanis, Roger Olofsson Bagge, Erik Holmberg, Per Karlsson, Henrik Lindman, Pat W Whitworth, Elinor Sawyer, Chirag Shah, Steve Shivers, Frank Vicini, Bruce G Mann, Troy Bremer. Assessmentof DCISionRT for guiding radiotherapy of DCIS in Sweden [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 P3-18-01.

Prognostic and Predictive Value of HER2 Expression in Ductal Carcinoma In Situ: Results from the UK/ANZ DCIS Randomized Trial.

HER2 is overexpressed more frequently in ductal carcinoma in situ (DCIS) than in invasive breast cancer but its prognostic significance and predictive role for radiotherapy has not been clearly established. We investigated the prognostic and predictive value of HER2 overexpression in DCIS. HER2 expression was evaluated by IHC using the HercepTest™ in samples from UK/ANZ DCIS trial participants (n = 755) with IHC 3+ expression categorized as HER2 positive for primary analyses. Sensitivity analyses included HER2 categorization as negative (IHC 0,1+), equivocal (IHC 2+), and positive (IHC 3+) and analyses restricted to a nested case-control component where 181 cases (with recurrence) were matched to 362 controls by treatment arm and age. Two-hundred and forty-five (34.4%) of evaluable 713 samples [181 ipsilateral breast events (IBE)] were HER2 positive. HER2 overexpression was associated with significantly increased risk of IBE [HR = 2.29; 95% confidence interval (95% CI), 1.64-3.14; P < 0.0001] and in situ IBE (DCIS-IBE; HR = 2.90; 95% CI, 1.91-4.40; P < 0.0001), but not of invasive IBE (I-IBE; HR = 1.40; 95% CI, 0.81-2.42; P = 0.23; Pheterogeneity = 0.04). Inclusion of HER2 significantly improved [Δχ2 (1d.f.) 12.25; P = 0.0005] a prognostic model of clinicopathological and treatment variables, HER2 being an independent predictor of IBE (multivariate HR = 1.91; 95% CI, 1.33-2.76; P = 0.0004). Radiotherapy benefit in preventing DCIS-IBE was significantly greater (Pheterogeneity = 0.04) in HER2-positive DCIS (HR = 0.16; 95% CI, 0.07-0.41) compared with HER2-negative DCIS (HR = 0.58; 95% CI, 0.28-1.19). HER2 overexpression is associated with significantly increased risk of in situ recurrence and is also predictive of radiotherapy benefit, with greater reductions in in situ but not invasive recurrences in HER2-positive DCIS.

Breast Irradiation in Ductal Carcinoma In Situ.

There is strong and consistent evidence that whole breast irradiation after breast conserving surgery significantly decreases the risk of ipsilateral breast events, in situ or invasive, underpinning its established role in patients with ductal carcinoma in situ (DCIS). Pending publication of the full results of BIG 3-07/TROG 07.01 randomised trial, addition of tumour bed boost to whole breast irradiation is recommended in the presence of adverse clinical-pathologic features, and the use of moderately hypofractionated whole breast dose-fractionation schedules is supported. As published data supporting the use of adjuvant partial breast irradiation in patients with low-risk DCIS are limited, its off-study application should be limited to low-risk patients defined by international and national guidelines. Finally, low-risk patients may not derive clinically meaningful benefits from radiation therapy and research on molecular profiling is ongoing to improve prognostic precision and guide safe omission of radiation therapy after breast conserving surgery.

A Comparison of Predicted Ipsilateral Tumor Recurrence Risks in Patients With Ductal Carcinoma in Situ of the Breast After Breast-Conserving Surgery by Breast Radiation Oncologists, the Van Nuys Prognostic Index, the Memorial Sloan Kettering Cancer Center DCIS Nomogram, and the 12-Gene DCIS Score Assay

PurposeTo compare ipsilateral breast event (IBE) risks in patients with ductal carcinoma in situ of the breast (DCIS) post-lumpectomy, as estimated by breast radiation oncologists, the Van Nuys Prognostic Index, the Memorial Sloan Kettering Cancer Center (MSKCC) DCIS nomogram, and the 12-gene Oncotype DX DCIS score assay. Methods and MaterialsConsecutive DCIS cases treated with lumpectomy from November 2011 to August 2014 with available DCIS score results were identified. Three radiation oncologists independently estimated the 10-year IBE risk. The Van Nuys Prognostic Index and MSKCC nomogram 10-year IBE risk estimates were generated. Differences and correlations between the IBE estimates and clinicopathologic factors were evaluated. ResultsNinety-one patients were identified for inclusion. Forty-eight percent would have been ineligible for the E5194 study. The mean risk of IBE from the DCIS score assay was 12.4%, compared with a range of 18.9% to 26.8% from other sources. The mean IBE risk from the DCIS score assay was lower regardless of E5194 eligibility. The MSKCC nomogram and DCIS score assay risk estimates were weakly correlated with each other (P = .23) and were each moderately correlated with the other risk estimates (P = .41-.56). When applying the radiation oncologists’ treatment recommendations based on their proposed risk cutoffs, evaluating risk according to the DCIS score assay led to the highest proportion of patients recommended excision alone. ConclusionsIBE risk estimates for this general community cohort of DCIS cases vary significantly among commonly available clinical predictive tools and individual radiation oncologist estimates. Surgical margins and tumor size continue to factor prominently in radiation oncologist decision algorithms. The differences found between the IBE risk estimate methods suggests that they are not interchangeable and the methods that rely on clinicopathologic features may tend to overestimate risk.

Prognostic Score-Based Stratification Analysis Reveals Universal Benefits of Radiotherapy on Lowering the Risk of Ipsilateral Breast Event for Ductal Carcinoma In Situ Patients with Different Risk Levels.

We aimed to analyze the effects of radiotherapy (RT) on the incidence rate of ipsilateral breast event (IBE) in ductal carcinoma in situ (DCIS) patients with lumpectomy after being stratified by prognostic score. We identified DCIS patients who received lumpectomy, from the Surveillance, Epidemiology, and End Results (SEER) database from 1988 to 2015. Cumulative incidence functions for competing risk were used to evaluate the effects of RT on IBE risk over time. Three multivariate regression models (weighted, non-weighted, and Fine-Gray) were applied to compare the IBE risk between the RT and non-RT groups after stratifying patients by prognostic score. Overall, 72,623 DCIS patients were identified from the SEER database and 49,206 (66.8%) patients received RT. During the follow-up period (ranging from 7 to 347months), the cumulative probability of invasive and in situ IBE was significantly lower in the RT group than in the non-RT group (p < 0.001). After being stratified by prognostic score, the weighted IBE incidence rate increased as the risk level increased (p < 0.050). In multivariate regression models, RT lowered the IBE incidence rate by at least 30% in low-, moderate-, and high-risk DCIS (p < 0.010). In particular, the in situ and invasive IBE incidence rate decreased by over 50% in low-risk DCIS with RT (p < 0.001). RT is associated with a lowered IBE incidence rate in DCIS patients, regardless of the assigned risk levels for patients. The significant reduction in the IBE incidence rate in low-risk DCIS patients also indicates the potential benefits for recommending RT to such a patient population in clinical practice.

Abstract P2-08-57: A biologic signature to predict ipsilateral breast event risk at 10 years for early breast cancer

Abstract Background Outcomes for women with early breast cancer have continually improved. A biologic signature to identify those patients that have elevated ipsilateral breast event (IBE) risk after breast conserving surgery (BCS) treated with or without radiation therapy (RT) is needed. More aggressive systemic or surgical options may be warranted for patients with elevated risk while BCS alone may be an option for very low risk patients. We report early results for a biologic signature interrogating critical pathways. Material and Methods This study includes patients from Uppsala University Hospital and Västerås Hospital diagnosed with early breast cancer, 20mm or less, treated surgically between 1987 and 2004. Women with lymph node metastases or treated with mastectomy or chemotherapy were excluded. A panel of biomarkers (HER2, PR, Ki67, COX2, p16/INK4A, FOXA1 and SIAH2) were assayed and scored in PreludeDx's CLIA lab by board-certified pathologists. There were 171 eligible patients with biomarker data; 131 received RT and 9 received hormone therapy. Risk groups were calculated using biomarkers and clinical factors age and size. Absolute 10-year IBE risk was assessed using Kaplan-Meier survival analysis. Hazard ratios (HR) were determined using Cox proportional hazards analysis. Results There were 49 IBEs recorded. The biologic signature classified 41% of women into a low risk group. Patients in the elevated risk group had a significantly increased risk of 10-year IBE compared to those in the low risk group (Table 1). The HR for elevated vs. low risk group was 5.0 [2.2-11], p&amp;lt;0.001, in a multivariate analysis of risk group and RT. Patients in the elevated risk group treated with BCS and RT had an 18% apparent risk difference in 10-year IBE. Patients in the low risk group had similar low 10-year risks of IBE, when treated with BCS, with or without RT. The low risk women had somewhat increased prevalence of low grade tumors (58% vs. 41%). Women with low grade and small tumors (up to 10mm) were classified into both risk groups (54% low vs. 38% elevated risk). Table 1:10-year Risks of Local Recurrence by Risk GroupBCS without RTBCS plus RTN10-Yr local IBE Risk, 95%CIn10-Yr local IBE Risk, 95%CIBaseline4028%, [11% – 31%]13122% [12% – 24%]Low Risk Group196% [0%-14%]516% [0%-12%]Elevated Risk Group2149% [20%-68%]8031% [21% - 41%] Discussion A biologic risk signature identified early breast cancer patients with low and elevated 10-year IBE risks for women treated with BCS with or without RT and no chemotherapy. Approximately 40% of women were classified into a low risk group with a 0.5% IBE risk per year. Women in the elevated risk group had 3% to 5% IBE risks per year depending on treatment. Treatment for women in this observational study was neither randomized nor strictly rules based. With further prospective validation, the biologic signature identified herein may provide a tool enabling improved management for women diagnosed with early breast cancer. Citation Format: Bremer T, Savala J, Leesman G, Wärnberg F, Sund M, Wadsten C, Whitworth PW. A biologic signature to predict ipsilateral breast event risk at 10 years for early breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-57.

A Biological Signature for Breast Ductal Carcinoma In Situ to Predict Radiotherapy Benefit and Assess Recurrence Risk.

Ductal carcinoma in situ (DCIS) patients and their physicians currently face challenging treatment decisions with limited information about the individual's subsequent breast cancer risk or treatment benefit. The DCISionRT biological signature developed in this study provides recurrence risk and predicts radiotherapy (RT) benefit for DCIS patients following breast-conserving surgery (BCS). A biological signature that calculates an individualized Decision Score (DS) was developed and cross-validated in 526 DCIS patients treated with BCS ± RT. The relationship was assessed between DS and 10-year risk of invasive breast cancer (IBC) or any ipsilateral breast event (IBE), including IBC or DCIS. RT benefit was evaluated by risk group and as a function of DS. The DS was significantly associated with IBC and IBE risk, HR (per 5 units) of 4.2 and 3.1, respectively. For patients treated without RT, DS identified a Low Group with 10-year IBC risk of 4% (7% IBE) and an Elevated Risk Group with IBC risk of 15% (23% IBE). In analysis of DS and RT by group, the Elevated Risk Group received significant RT benefit, HR of 0.3 for IBC and IBE. In a clinicopathologically low-risk subset, DS reclassified 42% of patients into the Elevated Risk Group. In an interaction analysis of DS and RT, patients with elevated DS had significant RT benefit over baseline. The DS was prognostic for risk and predicted RT benefit for DCIS patients. DS identified a clinically meaningful low-risk group and a group with elevated 10-year risks that received substantial RT benefit over baseline.

Abstract GS5-08: A validation of DCIS biological risk profile in a randomised study for radiation therapy with 20 year follow-up (SweDCIS)

Abstract Background: Women diagnosed with ductal carcinoma in situ (DCIS) and their physicians need tools that assess individualized risk and predict treatment benefit. A DCIS biologic signature was previously validated in an observational study at Kaiser Permanente NW. We evaluated the results of the signature for predictive utility in a national randomized clinical trial (SweDCIS) by assessing the 10-year benefit of adjuvant radiotherapy (RT) on ipsilateral breast event (IBE) and invasive breast cancer (IBC) risks. Methods: The signature was validated in a prospective-retrospective study in women from the SweDCIS trial (n=1046) performed by the Swedish Breast Cancer Group. Women were treated with breast conserving surgery (BCS) between 1987-1999 and randomized to RT or no RT. A central pathology review of paraffin embedded tissue blocks (n=873) was performed at Uppsala University (UU). Freshly cut slides were provided to PreludeDx for biomarker testing. Extended follow-up of SweDCIS was published in 2014. A panel of biomarkers (HER2, PR, Ki67, COX2, p16/INK4A, FOXA1 and SIAH2) were assayed and scored in PreludeDx's CLIA lab by board-certified pathologists. Continuous Decision Scores (DS) were calculated with the biologic signature using the biomarker and clinical factors (age, size, margin, and palpability) blinded to patient outcome. The DS results were provided to the Uppsala Regional Cancer Center for analysis. A predefined and co-developed statistical analysis plan was executed. Absolute 10-year RT benefit was assessed using Kaplan-Meier survival analysis. Hazard ratios (HR) were determined using Cox proportional hazards analysis and the interaction of the DS and RT benefit was assessed. Results: Complete biomarker and clinical information was available in 584 women. In women with clear margins (n=506), 78 IBEs, including 31 IBCs, were recorded within 10 years of diagnosis. The multivariate analysis of DS (0-10 unit scale) and the RT interaction was significant for risk of IBC (p=0.048) and IBE (p&amp;lt;0.001) at 10 years. The DS defined an elevated risk group (&amp;gt;3) for which there was pronounced 10-year benefit of RT (p=0.01) with an absolute risk reduction of 9% for IBC (Table 1). The corresponding low risk group (≤3), which included 48% of all patients, demonstrated no significant RT benefit (p=0.70) with an absolute risk reduction of 1%. The continuous DS variable was correlated with IBE risk, HR 1.49/per 5 units 95%CI[1.02,2.18] (p=0.038), in addition to the RT benefit for IBE in low (p=0.04) and elevated (p&amp;lt;0.001) risk groups. Table 1. 10-year RT benefit in women from the SweDCIS trial.DS Risk GroupsIBC eventsIn Situ or IBC eventsnAbsolute RT-benefitHR [95%CI] Absolute RT-benefit HR [95%CI]Low Risk Group (DS≤3)2431%0.83 [0.32, 2.16]9%0.48 [0.24-0.97]Elevated Risk Group (DS&amp;gt;3)2639%0.24 [0.08, 0.73]17%0.31 [0.17-0.59] Discussion: Evaluation of the SweDCIS trial validated prognostic and RT predictive utility of the biologic signature. Women diagnosed with DCIS and treated with BCS±RT were stratified into clinically relevant low and elevated risk groups (≤3 vs &amp;gt;3). Women in the elevated risk group had twice the treatment benefit for IBC from RT compared to prior randomized trials, while the low risk group had no benefit from RT. Citation Format: Wärnberg F, Garmo H, Folkvaljon Y, Holmberg L, Karlsson P, Sandelin K, Linke S, Lyle S, Simin K, Leesman G, Barry T, Savala J, Whitworth P, Bremer T. A validation of DCIS biological risk profile in a randomised study for radiation therapy with 20 year follow-up (SweDCIS) [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 GS5-08.

Effect of radiotherapy after breast-conserving surgery in older patients with early breast cancer and breast ductal carcinoma in situ: a meta-analysis

BackgroundThere are no consistent agreements on whether radiotherapy after breast-conserving surgery (BCS) could provide local control and survival benefit for older patients with early breast cancer or breast ductal carcinoma in situ (DCIS). The present study aimed to evaluate the efficacy of radiotherapy after BCS in older patients with early breast cancer or DCIS.ResultsRadiotherapy could reduce the risk of local relapse in older patients with early breast cancer. The 5-year AR of local relapse was 2.2% and 6.2% for radiotherapy and non-radiotherapy group, respectively, with low 5-year ARD of 4.0% and high NNT of 25. The 10-year AR of local relapse was 5.3% and 10.5% for radiotherapy and non-radiotherapy group, respectively, with the 10-year ARD of 5.2% and NNT of 20. However, radiotherapy could not improve survival benefits, including overall survival, cancer-specific survival, breast-cancer-specific survival, and distant relapse. Moreover, radiotherapy could reduce the risk of ipsilateral breast events in older patients with DCIS.Materials and MethodsPubMed and Embase database were searched for relevant studies. Hazard ratios (HRs), risk ratios (RRs), absolute risk (AR), absolute risk difference (ARD), and number needed to treat (NNT) were used as effect measures to evaluate the efficacy of radiotherapy in older patients.ConclusionsOur study indicates that radiotherapy could slightly reduce the risk of local relapse in older patients with favorable early breast cancer. However, radiotherapy cannot translate into significant survival benefits.

Abstract P1-09-06: Prognostic and predictive relevance of cell cycle progression (CCP) score in ductal carcinoma in situ: Results from the UK/ANZ DCIS trial

Abstract Background: The prognostic abilities of most gene expression signatures in breast cancer are often due to detection of proliferative activity measured from expression of genes regulated as a function of cell cycle progression. Cell Cycle Progression (CCP) score is an important prognostic factor in prostate cancer, and has shown promising results for renal and lung cancer; its role in ductal carcinoma in situ (DCIS) has not been explored. We investigated the prognostic and predictive relevance of CCP Score in DCIS using material from UK/ANZ DCIS trial. Methods: Formalin-fixed paraffin embedded tissues were collected from patients enrolled in the UK/ANZ DCIS trial, a randomised 2X2 factorial design trial investigating role of tamoxifen, radiotherapy (RT) or both as adjuvant treatment in DCIS. mRNA expression of 25 S- and M-phase CCP genes was evaluated by reverse transcription followed by PCR on customized Taqman low-density arrays. CCP score is an un-weighted average of the expression values of CCP genes after normalisation with 14 housekeeping genes. CCP score was analysed as a continuous variable and also as an ordinal variable using tertile-based cut-offs. Exploratory analyses with subgroups defined by HER2 status by immunohistochemistry were performed. Results: CCP scores were evaluable in 521 (134 recurrence events) of 704 available samples (DCIS absent or insufficient RNA in 51, assay failure in 132). Increase in CCP score (median 1.15; IQR 0.71-1.74) was associated with increased risk of ipsilateral breast event (IBE) [Hazard ratio (HR) = 1.28; 95% Confidence Interval (95%CI) 1.08-1.51; p = 0.0049]. CCP score however was not an independent predictor in multivariate analyses [HR = 1.16; 95%CI 0.95-1.42; p = 0.14]. CCP scores were categorised as CCP low (&amp;lt;0.87), CCP intermediate (&amp;gt;/= 0.87 to &amp;lt; 1.52) and CCP high (&amp;gt;/= 1.52) by tertiles. The benefit of RT in reducing IBE was significant when CCP score was low [HR = 0.35; 95%CI 0.14-0.87; p = 0.024] or intermediate [HR = 0.23; 95%CI 0.09-0.59; p = 0.0023], however, those with high CCP score did not derive significant RT benefit [HR = 0.59; 95%CI 0.31-1.13; p = 0.11]. In exploratory subgroup analyses, HER2 negative DCIS with high CCP score (20.9% of all DCIS cases) did not derive RT benefit and the largest RT benefit was seen for DCIS that expressed HER2 and did not have a high CCP score (23.2% of all DCIS cases). Benefit of RT and 10-year IBE rates by CCP score (categorised) and HER2 status subgroups.SubgroupneventsHR (95%CI)p10-year IBE rates (%) - No RT10-year IBE rates (%) - RTCCP-high &amp; HER2 neg106220.83 (0.35-1.97)0.6722.5 (14.0-35.0)20.0 (10.5-36.0)CCP-high &amp; HER2 pos67210.43 (0.16-1.17)0.09840.6 (27.1-57.6)20.4 (8.9-42.9)CCP-non-High &amp; HER2 neg217300.43 (0.18-0.99)0.04816.2 (10.7-24.0)8.1 (4.0-16.3)CCP- non-High &amp; HER2 pos118330.14 (0.04-0.46)0.001239.5 (29.3-51.6)7.1 (2.3-20.4)CCP-non-High = low or intermediate CCP score Conclusions: CCP score is not independently associated with the risk of IBE but appears to be a predictor of RT benefit. Exploratory analyses suggest that combined with HER2 status, it may help in identifying a large DCIS subgroup where RT is highly indicated and another large subgroup where mastectomy may be merited. Citation Format: Thorat MA, Wagner S, Jones LJ, Levey PM, Bulka K, Hoff R, Sangale Z, Flake II DD, Bundred NJ, Fentiman IS, Forbes JF, Lanchbury JS, Cuzick J. Prognostic and predictive relevance of cell cycle progression (CCP) score in ductal carcinoma in situ: Results from the UK/ANZ DCIS trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-09-06.

Abstract P1-11-02: A comparison of models (physician, the Van Nuys prognostic index, the Memorial-Sloan-Kettering Cancer Center DCIS nomogram)to predict ipsilateral breast events in patients with ductal carcinoma in situ (DCIS) of the breast after breast-conserving surgery failed to replicate results of the oncotype DCIS recurrence score

Abstract Purpose: To compare ipsilateral breast event (IBE) risks in patients with DCIS of the breast post-lumpectomy, as estimated by breast radiation oncologists, the Van Nuys Prognostic Index (VNPI) studies, the Memorial Sloan Kettering Cancer Center (MSK) DCIS nomogram, and the 12-gene DCIS Recurrence Score assay. Materials/Methods: 12-gene DCIS Recurrence Score of 91 DCIS lumpectomy cases were identified from our practice. Clinicopathologic factors (excluding DCIS score) were summarized for blinded review. 3 radiation oncologists independently estimated the 10-year IBE risk and rated the impact of age/menopausal status, tumor morphology, tumor span, and margin width. Corresponding VNPI and MSK nomogram estimates were generated. Differences and correlations between the IBE estimates and clinicopathologic factors were evaluated with univariate and multivariate analysis. Results: Median age was 60, 25% margins &amp;lt; 3 mm, 48% DCIS span &amp;gt; 10 mm, 48% would have been ineligible for E5194. All comparisons were initially examined for similarity (non-significant differences) and susequently tested for a significant correlation. In three possible physician comparisons only 1 (AA-CL) had similar IBE estimates and strong correlation (r=0.792). Comparison of physicians to either VNPI nomogram or MSK DCIS calculator had similar estimates with strong correlation in only 2 of 6 possible comparisons in the all cases and the E5194 eligible patient cohorts respectively; and in 1 of 6 comparisons in the E5194 ineligible cohort. The DCIS Recurrence Score showed no strong correlation in regard to similar IBE estimates for any comparisons including either physicians, VNPI nomogram or MSK DCIS calculator. Tumor size was highly correlated with all physician IBE estimates (r = 0.547 to 0.799), while margin size showed moderate to high inverse correlations (r = -0.324 to -0.619). All 3 physicians rated margin width as having the most impact on their IBE risk estimates, then tumor morphology and tumor span. Source of EstimateAll Cases (n = 91)E5194 Eligible (n = 47)E5194 Ineligible (n = 44)DCIS Score15.1%, 5.3 (14.0-16.2)14.2%, 4.8 (12.8-15.6)16.1%, 5.7 (14.3-17.8)MSK DCIS Nomogram (Rudloff et al., 2010)18.8%, 7.7 (17.2-20.4)23.4%, 18.6 (19.6-27.3)16.1%, 4.1 (14.9-17.3)21.7%, 9.4 (18.8-24.6)VNPI studies23.4%, 18.6 (19.6-27.3)15.6%, 15.5 (11.0-20.1)31.9%, 18.1 (26.4-37.4)AA18.9%, 14.1 (16.0-21.9)11.7%, 8.8 (9.1-14.3)26.6%, 14.7 (22.2-31.1)CL19.9%, 11.8 (17.5-22.4)14.5%, 6.6 (12.5-16.4)25.8%, 13.3 (21.7-29.8)DC26.8%, 13.9 (23.9-29.7)19.8%, 5.9 (18.1-21.6)34.2%, 16.1 (29.3-39.1) Conclusion: IBE risk estimates for this cohort of DCIS cases vary significantly among commonly available clinical predictive tools and individual physician estimates. Surgical margins and tumor size continue to factor prominently in physician decision algorithms. In our observations, neither the VNPI nomogram, MSK DCIS calculator nor physician IBE risk estimates have similar values with strong enough correlation to reliably replicate the DCIS Recurrence Score. Citation Format: Leonard C, Lei R, Antell A, Nowels M, Fryman S, Howell K, Dennis C. A comparison of models (physician, the Van Nuys prognostic index, the Memorial-Sloan-Kettering Cancer Center DCIS nomogram)to predict ipsilateral breast events in patients with ductal carcinoma in situ (DCIS) of the breast after breast-conserving surgery failed to replicate results of the oncotype DCIS recurrence score [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-11-02.

The prevalence and clinical relevance of tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ of the breast

Tumor-infiltrating lymphocytes (TILs) are a robust prognostic adjunct in invasive breast cancer, but their clinical role in ductal carcinoma in situ (DCIS) has not been ascertained. We evaluated the prevalence and clinical relevance of TILs in a well annotated series of 1488 consecutive DCIS women with a median follow-up of 8.2years. Detailed criteria for TILs evaluation were pre-defined involving the International Immuno-Oncology Biomarker Working Group. TILs percentage was considered both as a continuous and categorical variable. Levels of TILs were examined for their associations with ipsilateral breast event (IBE), whether in situ or invasive. Of the 1488 patients with DCIS under study, 35.1% had <1%, 58.3% 1-49% and 6.5% ≥50% peri-ductal stromal lymphocytes. The interobserver agreement in TILs evaluation, measured by the intraclass correlation coefficient (ICC) was 0.96 (95% CI 0.95-0.97). At univariable analysis, clinical factors significantly associated with TILs (P ≤0.001) were intrinsic subtype, grade, necrosis, type of surgery. Her-2 positive DCIS were more frequently associated with TILs (24% of patients with TILs ≥50%), followed by the triple negative (11%), Luminal B/Her-2 positive (9%) and Luminal A/B subtypes (1%) (P < 0.0001). We did not find any association between TILs as a continuous variable and the risk of IBEs. Likewise, when patients were stratified by TILs percentage (<1%, between 1% and 49.9%, and ≥50%), no statistically significant association was observed (10-year cumulative incidence of IBEs: 19%, 17.3%, and 18.7% respectively, P = 0.767). TILs occur more frequently in the Her-2 positive DCIS. Although we did not find a significant association between TILs and the 10-year risk of IBE, our data suggest that immunotherapies might be considered in subsets of DCIS patients.

Comparison of Risk of Ipsilateral Breast Event After Lumpectomy for Ductal Carcinoma In Situ, As Estimated by Breast Radiation Oncologists, Van Nuys Prognostic Index, Memorial Sloan Kettering Cancer Center DCIS Nomogram, and the 12-gene DCIS Score

Quality Consortium (MROQC), a statewide assessment of breast cancer patients undergoing radiation therapy and crude rates were used for comparisons. Results: For left sided cancers, mean heart dose was 3.09 Gy. The use of a breast cup resulted in mean V20 for lung of 5.6% and V5 of 11%. Mean dose to the contralateral breast was 3.29 Gy. Twenty patients (42.5%) experienced grade 2 skin toxicity; one patient (2.1%) experienced a grade 3 skin toxicity. Moist desquamation rates: 44.7% compared to 45.5% MROQC. Moist desquamation for patients with a BMI >35 was 52.2% vs 42.8% MROQC. For a breast volume >1550cc, moist desquamation was seen in 48.6% vs 45.5% MROQC. Conclusion: Our results indicate that use of the breast cup can allow for improved dose homogeneity with similar acute toxicities as compared with patients treated without the cup while minimizing the dose to the heart and lungs. Our clinical experience shows that breast cups can be used with ease, and allow for good setup reproducibility. It appears that the slight increase in moist desquamation was associated with increased BMI. In conclusion, we recommend that use of a breast cup be considered in appropriately selected patients with large or pendulous breasts. Author Disclosure: P.R. Sevak: None. K. Aldridge: None. C. Fraser: None. C.K. Glide-Hurst: None. E.M. Walker: ACR appropriateness criteria expert panel member; ACR. RTOG Foundation advisory board member; RTOG. Breast working group; NRG. health disparities working group member; NRG. Institutional PI for NRG; NRG.

A Multigene Expression Assay to Predict Local Recurrence Risk for Ductal Carcinoma In Situ

A Multigene Expression Assay to Predict Local Recurrence Risk for Ductal Carcinoma In Situ

Abstract P4-10-14: Risk of Ipsilateral Breast Events in Patients with Ductal Carcinoma In Situ after Local Excision

Abstract Purpose To determine the risk of ipsilateral breast events (IBE) in patients with ductal carcinoma in situ (DCIS) treated with local excision. Patients and Methods We retrospectively identified 692 patients who had undergone local excision from 1968 through 2007 at our institution with a final diagnosis of DCIS. Factors evaluated included age, race, method of detection, menopausal status, bloody nipple discharge, histological type, final margin status, grade, status at last follow-up and recurrence information. An IBE was defined as the development of breast cancer of invasive histology or DCIS (but not lobular carcinoma in situ) in the treated breast. Results At a median follow-up of 6.1 years, 47 (6.8%) IBEs occurred in the 692 patients. Among 47 IBE, 23 (48.9%) were DCIS and 19 (40%) were invasive cancer and 5 (10.6%) were unknown type of IBE. Patients with IBE were younger (53 Vs 57, P=0.04). Whether patients had final positive margin (4 patients) had no influence on IBE. Use of a Cox proportional hazards model showed that patients with high grade tumors and those who did not receive adjuvant radiation therapy (XRT) were more likely to have an IBE (Hazard ratio: 4.1, 95% CI:1.3-13.4, P=0.019). The 5-year rate of ipsilateral breast events for patients with grade III DCIS who did not undergo adjuvant radiation therapy was significantly higher than all others: 15% vs. 4.6% compared to grade I/II with XRT, 15% vs. 10% compared to grade I/II without XRT, and 15% vs. 9.9% in grade III with XRT (P=0.017). Conclusions Patients with low or intermediate grade DCIS have an acceptably low rate of ipsilateral breast events after local excision with adjuvant radiation therapy. Patients with high-grade lesions treated without irradiation have a rate of IBE of 15% at 6 years, suggesting that excision alone is inadequate treatment in this group. Further follow-up is necessary to document long-term results. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-10-14.