Abstract PD5-03: Ipsilateral invasive cancer risk after diagnosis with ductal carcinoma in situ in patients with and without index surgery: The effects of endocrine therapy and radiation treatment
Authors: Ryser Marc D , Rushing Christel N , Thomas Samantha M , Lynch Thomas , McCarthy Anne , Mohammed Zahed A , Francescatti Amanda B , Frank Elizabeth S , Partridge Anne H , Thompson Alastair M , Hyslop Terry , Hwang E. Shelley 
Published: February 2021

Abstract
Background. Ongoing clinical trials are evaluating active surveillance as a potential alternative to immediate surgery in patients diagnosed with low-risk ductal carcinoma in situ (DCIS). Among women undergoing lumpectomy, the risk of ipsilateral invasive breast cancer (iIBC) after a diagnosis of DCIS can be reduced with adjuvant therapy, including endocrine therapy (ET) and radiation treatment (RT). Here we characterize the effects of ET and RT on iIBC risk after diagnosis with DCIS in a national cohort, in patients who received breast conserving surgery (BCS) within 6 months of diagnosis (BCS group) compared to patients who did not receive any locoregional treatment within 6 months of diagnosis (surveillance [SV] group). Methods. A treatment-stratified random sample of patients diagnosed with biopsy-confirmed DCIS in 2008-14 was selected from 1,330 Commission on Cancer-accredited facilities (20/site). Patients who received a mastectomy within 6 months of diagnosis were excluded. Subsequent breast events were abstracted up to 10 years after diagnosis. Primary outcomes were the population-averaged 8-year absolute risks of iIBC for the following five treatment modalities: BCS alone, SV alone, BCS + ET, SV+ET, BCS+RT, and BCS+ET+RT (where ET was defined as ≥5 years of continuous treatment). Secondary outcomes were the average treatment effects (ATE) of SV+ET vs SV, BCS+RT vs SV+ET, and BCS+RT+ET vs SV+ET. A propensity score (PS) model for treatment choice BCS vs SV was fitted with sampling design (SD) weighting and random effects for patients within facilities. Relative treatment effects (hazard ratios [HR]) for the five treatment groups were obtained using multivariable Cox proportional hazards models adjusted for tumor and patient characteristics. The models were weighted by SD and PS and included a robust sandwich covariance estimator to account for clustering of patients within facilities. Population-averaged risks and ATEs were derived from the marginal outcome probabilities: assuming that the entire population received the treatment of interest, each patient’s counterfactual probability of an iIBC event by 8 years was predicted, and then averaged across the weighted population. 95% confidence intervals (CI) were obtained by bootstrapping. Results. The final analytic cohort contained 14,245 (88.2%) BCS and 1,914 (11.8%) SV patients. Overall, median age at diagnosis was 61 years (IQR: 52-69) and median follow-up was 5.8 years (95% CI 5.7-6.1). The majority of patients were Caucasian (81.9%), with hormone receptor-positive (79.9%), and nuclear grade I/II (54.5%) DCIS. Uptake of any ET was 48.5% and 23.7% in BCS and SV patients, respectively. The relative treatment effects (HR) for the receipt of BCS, RT and ≥5 years of ET were 1.65 (95% CI: 1.14-2.39), 0.40 (95% CI: 0.27-0.61) and 0.55 (95% CI: 0.17-1.72) respectively. The 8-year population-averaged iIBC risks and corresponding ATEs are shown Table 1. Conclusion. The 8-year risk of iIBC was below 7% for all six management options. Relative and absolute treatment effects of ET and RT were comparable to previously reported estimates. In SV patients, receipt of ≥5 years of ET nearly halved the 8-year risk, indicating a substantial risk reduction potential for ET in patients who do not receive immediate surgery after diagnosis.
Table 1: Population-averaged 8-year iIBC risk and ATEs.TreatmentiIBC risk (%)95% CISurveillance6.906.79-7.01Surveillance + ET3.903.83-3.96BCS4.264.21-4.31BCS + RT1.761.73-1.79BCS + ET2.392.35-2.43BCS + ET + RT0.980.96-0.99Treatment comparisonATE (%)95% CISV+ET vs SV3.02.95-3.04BCS+RT vs SV+ET2.142.11-2.17BCS+RT+ET vs SV+ET2.922.78-2.97
Citation Format: Marc D Ryser, Christel N Rushing, Samantha M Thomas, Thomas Lynch, Anne McCarthy, Zahed A Mohammed, Amanda B Francescatti, Elizabeth S Frank, Anne H Partridge, Alastair M Thompson, Terry Hyslop, E. Shelley Hwang. Ipsilateral invasive cancer risk after diagnosis with ductal carcinoma in situ in patients with and without index surgery: The effects of endocrine therapy and radiation treatment [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD5-03.