Jelle Wesseling MD PhD; 2026 EBCC: ‘Lord’ Trial Finds Active Surveillance for Estrogen-Receptor-Positive, HER2- Negative, Grade 1–2 DCIS Just As Effective as Standard Therapy

‘Lord’ Trial Finds Active Surveillance for Estrogen-Receptor-Positive, HER2-Negative, Grade 1–2 DCIS Just As Effective as Standard Therapy

An interview with:

Jelle Wesseling MD PhD, Pathologist, Medical Director, Early Cancers Detection Centre, Netherlands Cancer Institute, Division of Molecular Pathology, Amsterdam, The Netherlands.

BARCELONA, Spain: Because low-risk ductal carcinoma in situ (DCIS) is often unlikely to progress to breast cancer, de-escalating therapy was on the agenda of the Lord trial of active surveillance, that was reported at the 2026 European Breast Cancer Conference. The findings were reassuring: So much so that randomization was stopped early. The lead study author, pathologist Jelle Wesseling MD PhD who is Medical Director of the Early Cancers Detection Centre at the Netherlands Cancer Institute in Amsterdam, gave the details to the Audio Journal of Oncology’s Peter Goodwin.

AUDIO JOURNAL OF ONCOLGY: Jelle Wesseling MD PhD

IN: [GOODWIN]” I am at the European Breast ….

OUT:  ….of Oncology, I’m Peter Goodwin 10:34secs

EBCC 2025 Abstract no: 2LBA:

“De-escalating treatment for low-risk Ductal Carcinoma In Situ: early safety of active surveillance without endocrine therapy in the prespecified interim analysis of the LORD-trial* (BOOG 2014-04)”

Authors:

Wesseling1,2,3,4, M. Nieberg1, S. Aleikhaneshir1, L. Elshof1, R. Schmitz1, C. Sondermeijer5, S. Balduzzi5, K. Pengel5, J. Weiner1, M. Gerritsma6, E. Engelhardt6, E. Bleiker6, E. Verschuur7, I. Langerak8, R. Mann9, E. van Leeuwen-Stok10, E. Lips1, N. Bijker11, F. van Duijnhoven12

1The Netherlands Cancer Institute, Division of Molecular Pathology, Amsterdam, The Netherlands

2Leiden University Medical Center, Department of Pathology, Leiden, The Netherlands

3 The Netherlands Cancer Institute, Center of Early Cancer Detection, Amsterdam, The Netherlands

4The Netherlands Cancer Institute, Department of Pathology, Amsterdam, The Netherlands

5The Netherlands Cancer Institute, Biometrics Department, Amsterdam, The Netherlands

6The Netherlands Cancer Institute, Division of Psychosocial Research and Epidemiology, Amsterdam, The Netherlands

7Europa Donna & Dutch Breast Cancer Patient Association BVN, Patient Advocacy, Utrecht, The Netherlands

8Dutch Breast Cancer Patient Association BVN, Patient Advocacy, Utrecht, The Netherlands

9The Netherlands Cancer Institute, Department of Radiology, Amsterdam, The Netherlands

10BOOG Study Center, National Breast Cancer Trial Coordination, Utrecht, The Netherlands

11The Netherlands Cancer Institute, Depratment of Radiation Oncology, Amsterdam, The Netherlands

12The Netherlands Cancer Institute, Department of Surgical Oncology, Amsterdam, The Netherlands

Background

Active surveillance has been proposed as a de-escalation strategy for women with low-risk ductal carcinoma in situ (DCIS). The LORD-trial evaluates the safety of active surveillance compared with standard treatment in women with estrogen-receptor-positive, HER2- negative, grade 1–2 DCIS.

Methods

The LORD-trial is a multicentre study that followed a patient-preference design after initial randomization proved infeasible. The primary endpoint is ipsilateral invasive breast cancer (iiBC)-free rate at 10 years. A prespecified, non-binding interim futility analysis was planned after 60 iiBC events.

Results

DSMB prespecified interim analysis

1,423 women had been enrolled with a median follow-up of 23 months. The first n=73 were randomized between the two arms. After transforming to a patient preference design, n=1,025 patients opted for active surveillance and n=330 for standard treatment. No patients received endocrine therapy. On an intention-to-treat basis, iiBC occurred in 4/363 (1%) women allocated to standard treatment and 63/1,060 (6%) women undergoing active surveillance. Based on these findings, the Data Safety Monitoring Board (DSMB) advised cessation of registration and recruitment, while continuing follow-up of enrolled patients.

Cohort analysis

When iiBCs detected at primary surgery in the standard-treatment group were additionally considered, cumulative iiBC incidence was similar between strategies: 33/363 (9%) in the standard-treatment arm and 63/1060 (6%) in active surveillance. Cases with full pathology characteristics available – for 31 and 55, respectively – were compared between the two arms (Table 1).

Conclusions

The prespecified DSMB interim analysis resulted in a recommendation to stop inclusion for reasons of futility, leading to early closure of trial inclusion. Follow-up of included women was recommended and is ongoing to assess long-term outcomes and inform the safety of de-escalation strategies for DCIS.

Table 1. Comparison iiBCs with fully known pathology characteristics per arm in the cohort analysis

https://cm.eortc.org/cmPortal/Searchable/ebcc15/config/Normal#!abstractdetails/0000992920

 https://clinicaltrials.gov/study/NCT02492607

Jelle Wesseling Audio Journal of Oncology TEXT

April 2nd, 2026