Abstract OT3-07-01: Update of the randomized, non-inferiority LORD trial testing safety of active surveillance for women with screen-detected low risk ductal carcinoma in situ (EORTC-1401-BCG/BOOG 2014-04, DCIS)
Authors: Wesseling J , Elshof LE , Tryfonidis K , Poncet C , Aalders K , van Leeuwen-Stok E , Skinner V , Loo C , Winter-Warnars G , Bleiker E , Retèl V , Pijnappel R , Bijker N , Rutgers E , van Duijnhoven F 
Published: February 2018

Abstract
The introduction of population-based breast cancer screening and implementation of digital mammography have led to an increased incidence of ductal carcinoma in situ (DCIS) without a decrease in the incidence of advanced breast cancer. This suggests DCIS overdiagnosis exists.
We hypothesize that asymptomatic, low-grade DCIS can safely be managed by active surveillance. If progression to invasive breast cancer would still occur, this will be low-grade and hormone receptor positive with excellent survival rates. Also, breast-conserving treatment will still be an option, if no prior radiotherapy has been applied. Management by active surveillance also may save many low-grade DCIS patients intensive treatment.
Therefore, we will compare active surveillance with conventional treatment, being either mastectomy, wide local excision (WLE) only, or WLE plus radiotherapy, possibly followed by hormonal therapy for primary low-grade DCIS. For this, we conduct a phase III, open-label, non-inferiority, multi-center, randomized clinical trial sponsored by the European Organization for Research and Treatment of Cancer (EORTC-1401-BCG). The Dutch Centers are coordinated by the Dutch Breast Cancer Research Group (BOOG) (BOOG 2014-04). This trial is developed and implemented in close collaboration with patient advocates.
Randomization will be in a 1:1 ratio among one of the following arms: (1) active surveillance or (2) standard treatment per local policy. In total, 1,240 women (≥ 45 years) will be included without prior breast cancer, but with asymptomatic, pure, low-grade DCIS, based on a minimum of tissue harvested by biopsy from calcifications detected by population-based or opportunistic screening. Assuming 25% of randomized women qualified to enroll in the study will drop out or will be excluded from per protocol evaluation, at least 1,240 women need to be randomized to obtain the 930 patients required for the evaluation of the primary endpoint. The same follow-up scheme will be applied in both study arms, i.e. annual mammography for a period of 10 years. The primary end-point is ipsilateral invasive breast tumor-free rate at 10 years. Secondary end-points are among others: overall survival, breast cancer-specific survival, mastectomy rate, patient reported outcomes and cost-effectiveness. Accrual has started in the Netherlands in February 2017 and will start internationally in over 30 centers shortly.
Acknowledgements: This trial is funded by Pink Ribbon Netherlands, the Dutch Cancer Society and Dutch Cancer Society/Alpe d'HuZes, and Cancer Research UK.
Citation Format: Wesseling J, Elshof LE, Tryfonidis K, Poncet C, Aalders K, van Leeuwen-Stok E, Skinner V, Loo C, Winter-Warnars G, Bleiker E, Retèl V, Pijnappel R, Bijker N, Rutgers E, van Duijnhoven F. Update of the randomized, non-inferiority LORD trial testing safety of active surveillance for women with screen-detected low risk ductal carcinoma in situ (EORTC-1401-BCG/BOOG 2014-04, 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 OT3-07-01.