Abstract P5-11-02: Predicting local recurrence in patients treated for ductal carcinoma in situ of the breast (DCIS)
Authors: Martinez-Perez C , Turnbull AK , Ekatah GE , Arthur LM , Fernando A , Sims AH , Thomas JS , Dixon JM 
Published: February 2018

Background: Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of precursor, non-invasive breast lesions. Currently we lack accurate tools to stratify DCIS patients according to inherent risk of in breast tumour recurrence (IBTR) or progression to invasive breast cancer (IBC).Most DCIS patients are treated by breast-conversing surgery (BCS), followed by whole-breast radiotherapy (RT) for the majority of high-grade DCIS. The aim of this study was to identify novel biomarkers which predict recurrence after BCS +/- RT.

Methods: A single institution study of 466 consecutive patients (median age 61, range 35-94) with DCIS treated by BCS between 2000 and 2010 was carried out. 271 patients with grade 3 DCIS received RT and 155 with grade 1/2 DCIS did not receive RT.

For biomarker discovery, a case-control matched series of 200 patients (mean age = 61, range = 36-84) from the above audit that met the following criteria was selected:

· 120 with low/intermediate-grade DCIS treated with BCS alone: 30 have recurred, 90 patients matched 3:1 have not recurred by 10 years.

· 80 with high-grade DCIS treated by BCS plus RT: 20 have recurred, 60 patients matched 3:1 have not recurred by 10 years.

Median follow-up was 7.4 years. RNA has been extracted and Affymetrix Clariom S whole-genome analysis has been performed and is currently being analysed.

Results:

In the cohort of 466 patients, 271 patients with high grade DCIS had BCS plus RT. Actuarial IBTR and IBC-IBTR in this group were 10% and 4% at 5 years and 18% and 6% at 10 years, respectively. 155 patients with low/intermediate grade DCIS had BCS alone. Actuarial overall IBTR and IBC-IBTR in this group were 6% and 2% at 5 years and 13% and 2% at 10 years respectively.

In the high-grade, RT treated group, lesion size (P&lt;0.001, P=0.003), presence of comedo necrosis (P=0.018, P=0.025) and the Van Nuys Prognostic Index (VNPI) (P=0.02, P=0.004) were significantly associated with overall IBTR and DCIS-IBTR. No factor was significantly associated with IBS-IBTR in the high grade group and no factor predicted for any IBTR in the low/intermediate group.

Full genomic analysis of the 240 patient case-control matched cohort is underway and will be presented.

Discussion:

· This is the first DCIS biomarker discovery study using whole genome analysis and the matched cohort design looking separately at BCS + RT for high-grade DCIS and BCS only for low/intermediate grade DCIS.

· Clinical parameters alone may have insufficient sensitivity to identify high-grade, RT-treated patients at risk of developing IBC-IBTR.

· While recurrence rates in the low/intermediate grade DCIS group are lower than in the high-grade group, some patients do recur and there is a need to develop new tools which can identify low grade patients with a sufficiently high risk of recurrence to warrant additional treatment.

Citation Format: Martinez-Perez C, Turnbull AK, Ekatah GE, Arthur LM, Fernando A, Sims AH, Thomas JS, Dixon JM. Predicting local recurrence in patients treated for ductal carcinoma in situ of the breast (DCIS) [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 P5-11-02.