Abstract P4-15-08: Association of OncotypeDX® DCIS ScoreTM results with local recurrence in patients with DCIS treated on accelerated partial breast radiotherapy (APBI) protocols
Authors: Leonard CE , Fryman SP , Turner MP , Bennett JP , Carter DL , Sing AP 
Published: February 2018

Abstract
Background: Ductal carcinoma in situ (DCIS) is a proliferation of malignant epithelial cells of the ducts and terminal lobular units of the breast that do not invade the basement membrane. The incidence of DCIS has increased markedly since the early 1980s, chiefly due to screening mammography. Whole breast radiotherapy has largely been used to treat breast DCIS after lumpectomy. More recently, APBI has increasingly been utilized for breast DCIS. Currently updated American Society of Radiation Oncology (ASTRO) APBI guidelines have included "low risk" DCIS (as defined by RTOG 9804 criteria). The following results further explore clinico-pathologic factors, in addition to the DCIS Score, in order to better define an appropriate DCIS population for APBI.
Methods: An exploratory analysis aimed to retrospectively measure the association between clinico-pathologic factors and the DCIS Score result, an optimized 12-gene expression algorithm, and risk of any local failure (in situ or IBC recurrence) in a cohort of women treated with local excision and APBI on prospective phase II (NCT01185145) and phase III (NCT01185132) clinical trials. Multifocal tumors were described only by local pathology and not determined or defined centrally. The DCIS Score assay was performed by quantitative RT-PCR on formalin-fixed paraffin-embedded DCIS tumor specimens by Genomic Health (Redwood City, CA). Descriptive statistics of the cohort and assay results overall and by clinical trial were derived. Univariable Cox proportional hazards regression was used to determine whether there was an association between local failure and categorized DCIS Score group (≥39 vs &lt;39) or other clinico-pathologic factors on the pooled cohort of clinical trial patients.
Results: This analysis included 104 evaluable patients (N=18 from NCT01185145 and N=86 from NCT01185132). The median age was 60 (range: 41-80), 79% of patients were postmenopausal, and the median span of DCIS was 6 mm (range 2-25 mm). Over two-thirds of the cohort presented with necrosis (71%). The distribution of DCIS Score results ranged from 0 to 82, with 69% of patients having a DCIS Score result &lt;39. The median follow-up time was longer at 8.2 years in NCT01185145 versus 3.0 years in NCT01185132. There was a total of 6 local recurrences. DCIS Score result was significantly associated with local recurrence in univariable modeling (hazard ratio=10.3 for ≥39 vs &lt;39; p=0.0104). None of the other clinico-pathologic characteristics resulted in any significant correlation with locoregional recurrence. All results were highly variable due to the small number of events.
Conclusion: The DCIS Score assay demonstrated risk stratification in this cohort of patients treated with local excision and APBI pooled from two clinical trials. These results are consistent with those recently published by Rakovitch et al (J Natl Cancer Inst 2017). The cohort in this study was dominated by those in the phase III trial. Due to the small number of local recurrence events and limited follow-up time in the phase III trial, caution should be taken when interpreting the results. Further investigations are needed to confirm findings.
Citation Format: Leonard CE, Fryman SP, Turner MP, Bennett JP, Carter DL, Sing AP. Association of OncotypeDX® DCIS ScoreTM results with local recurrence in patients with DCIS treated on accelerated partial breast radiotherapy (APBI) protocols [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 P4-15-08.