Abstract P5-08-05: Risk of subsequent events after initial diagnosis of ductal carcinoma in situ - A large multi-center registry study
Authors: O'Keefe Thomas , Yau Christina , Jeong Eliza , Iaconetti Emma , Kim Paul , Griffin Ann , McGuire Joseph , Mukhtar Rita , Esserman Laura , Harismendy Olivier , Hirst Gillian L. 
Published: March 2020

Introduction: Ductal carcinoma in situ (DCIS) is a pre-malignant lesion but 14-53% will not progress to an invasive cancer. Large, well characterized DCIS datasets with long term follow up are sparse, and there is uncertainty regarding the long term effects of various treatment modalities on subsequent breast events (SBE). Here, we analyze trends identified in the SBE rates from patients treated at two large academic breast care centers in California, UCSF and UCSD.

Methods: Institutional Cancer Registries were used to collect demographic, clinical, imaging and pathologic data. Patients aged 18 years and older without any prior history of breast disease whose first diagnosed breast neoplasm was DCIS and who had at least 6 months of follow up were included. Only SBE beyond 6 months after initial diagnosis were included. All mastectomy types and associated adjuvant treatment were grouped. All patients not undergoing surgery were grouped. Differences between patients in the various treatment groups were assessed using χ2, Student’s t-test, and one-way ANOVA. Poisson regression was used to compare differences in SBE rates between treatment groups. For analysis, follow up times were divided into three 5 years periods (0-5, 6-10, 11-15 years) after initial DCIS diagnosis.

Results: 2730 patients - 1575 (57.7%) at UCSF and 1155 (42.3%) at UCSD - were diagnosed between 1985 and 2017 and included in the study. 1910 (70.0%) underwent breast conserving surgery (BCS), 672 (24.6 %) had mastectomy, 144 (5.3%) did not have surgery, and 4 (0.1%) had missing surgery status. 623 (22.8%) received adjuvant endocrine therapy (ET), 2081 (76.2%) did not and 26 (1.0%) had missing adjuvant endocrine therapy status. 1092 (40.0%) received adjuvant radiation therapy (RT), 1619 (59.3%) did not and 19 (0.7%) had unknown radiation therapy status. Median follow up time for all patients was 7.9 years. 305 patients were diagnosed with SBE. Of these, 144 (47.2%) were in situ and 147 (48.2%) were invasive including 16 (5.2%) metastatic lesions, and 14 (4.6%) had missing invasiveness. Of the 289 patients who did not have a metastatic second lesion, 176 (60.9%) SBE were ipsilateral, 88 (30.4%) were contralateral, and 25 (8.7%) had missing SBE laterality. The overall incidence (i) for any SBE over the entire study period was 1.4%/yr. Compared to women who were treated with BCS alone (N=642, i=2.14%/yr, 95% CI 1.76-2.51), SBE rates were lower in women undergoing BCS with RT (N=719, i=1.13%/yr, 95% CI 0.87-1.40, p&lt;0.001), BCS with RT and ET (N=356, i=0.63%/yr, 95% CI 0.30-0.97, P&lt;0.001), and mastectomy (N=672, i=1.00%/yr, 95% CI 0.75-1.25, p&lt;0.001) but were not significantly different for patients undergoing BCS with ET (N=159, i=2.25%/yr, 95% CI 1.35-3.15, p=0.813). Within the first 5 years of diagnosis, mastectomy, BCS with RT, and BCS with RT and ET all lowered the SBE rate of ipsilateral in situ and invasive SBE (p&lt;0.05, in each case). In contrast, no treatment modalities impacted the rate of contralateral SBE rate during any of the time periods. Importantly, the majority of patients, even with BCS alone never had a subsequent event and only 147 had an invasive event overall.

Conclusion: This large two-center registry study reveals that the rate of invasive and in situ SBE after an initial DCIS diagnosis are comparable. The effect of each treatment modality on SBE incidence rates are consistent with other published studies, with the notable exception of BCS and ET which requires deeper investigation. As expected, local treatment affects mostly ipsilateral events within the first 5 years after initial diagnosis, without impacting the rate of contralateral SBE. Complementary molecular and cellular profiling of selected specimens are underway to help build a more precise BSE risk model and prevent overtreatment.

Citation Format: Thomas O'Keefe, Christina Yau, Eliza Jeong, Emma Iaconetti, Paul Kim, Ann Griffin, Joseph McGuire, Rita Mukhtar, Laura Esserman, Olivier Harismendy, Gillian L. Hirst. Risk of subsequent events after initial diagnosis of ductal carcinoma in situ - A large multi-center registry study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-05.