Management of Low-risk (Grade I and II) DCIS
LORD
Management of Low Risk Ductal Carcinoma in Situ (Low-risk DCIS): a Non-randomized, Multicenter, Non-inferiority Trial; Standard Therapy Approach Versus Active Surveillance
3 other identifiers
interventional
2,500
1 country
60
Brief Summary
A substantial number of DCIS lesions will never form a health hazard, particularly if it concerns slow-growing low-risk DCIS (grade I and II). This implies that many women might be unnecessarily going through intensive treatment resulting in a decrease in quality of life and an increase in health care costs, without any survival benefit. The LORD (LOw Risk DCIS) study is a non-randomized, international, multicenter, phase III non-inferiority trial, and aims to determine whether screen-detected low-risk DCIS can safely be managed by an active surveillance strategy or that the conventional treatment, being either WLE alone, WLE + RT, or mastectomy, and possibly HT, should remain the standard of care.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Feb 2017
Longer than P75 for not_applicable
60 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 24, 2015
CompletedFirst Posted
Study publicly available on registry
July 8, 2015
CompletedStudy Start
First participant enrolled
February 13, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2034
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 1, 2034
January 26, 2026
January 1, 2025
17 years
June 24, 2015
January 23, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Ipsilateral invasive breast cancer-free rate at 10 years
Ipsilateral invasive breast cancer-free rate at 10 years (both therapeutic policies
10 years from inclusion
Secondary Outcomes (12)
Rate of invasive disease at the final pathology specimen (standard arm only)
from inclusion till time of invasive disease during 10 years at minimum
Rate of grade III DCIS at the final pathology specimen (standard arm only)
from inclusion till time of invasive disease during 10 years at minimum
Biopsy rate for ipsilateral breast during follow-up
from inclusion to the time of death, during 10 years at minimum
Masectomy rate for ipsilateral breast
from inclusion to the time of ipsilateral breast cancer or death, during 10 years at minimum
Time to ipsilateral grade III DCIS
from inclusion to the development of a new ipsilateral DCIS of grade III, up to 10 years
- +7 more secondary outcomes
Study Arms (2)
Standard treatment
ACTIVE COMPARATORStandard treatment according to local policy. This can be either wide local excision only, wide local excision and radiotherapy, or mastectomy. Hormonal therapy is also allowed. Follow-up:by annual digital mammography for a period of 5 years and a digital mammography at 7 and 10 years.
Active surveillance
EXPERIMENTALActive surveillance : monitoring by annual digital mammography for a period of 5 years and a digital mammography at 7 and 10 years.
Interventions
wide local excision only or wide local excision and radiotherapy or mastectomy. +/- hormonal therapy
Eligibility Criteria
You may qualify if:
- Written informed consent according to ICH GCP, and national andlocal regulations
- Women ≥ 45 years old, any menopausal status
- Unilateral DCIS grade I or II of any size
- American Society of Anesthesiologists (ASA) score 1-2 or 3, only if able to undergo surgery and yearly mammography
- Lesions of type 'calcifications only', detected by population-based or opportunistic screening mammography
- Within twelve weeks of detection, stereotactic biopsy has to be performed from the area of the calcifications. Preferably vacuum assisted biopsies. Alternatively, at least six 12 G needle biopsies (or the equivalent of six 12 G needles) may be used. ) . Whatever needle size is applied, it is essential to confirm that the biopsies contain representative calcifications via biopsy radiography, microscopy, or both.
- Estrogen receptor ≥ 80% positive and HER2 negative: 0 or 1+ or 2+ with negative ISH), analysed centrally by pathology at NKI-AVL
- In case of an extended lesion (\> 5 cm): biopsies were taken from the center and the periphery of the lesion, or from two peripheral parts of the lesion
- In case of multiple lesions with calcifications biopsies have been taken from two, but not more, groups of calcifications
- Marker placement at biopsy site (s) in the breast
- FFPE tissue blocks from the biopsy and, if applicable, from the resection specimen, are available for translational research purposes. If no FFPE tissue blocks can be submitted, 10 unstained slides of 4-5 micrometer thickness from the lesion(s) are acceptable
- Good correlation between pathological and radiological findings i.e. both findings confirm low-risk DCIS and no suspicion of high- grade DCIS or invasive breast cancer
You may not qualify if:
- Estrogen receptor negative: \<80% or HER2 positive: 3+, or 2+ with positive ISH
- Presence of either mass, increased focal density or architectural distortion around the calcifications on mammography (suspicious for invasive disease)
- Presence of Paget's disease, invasive breast cancer, or pleomorphic LCIS; Lobular neoplasia, referring to atypical lobular hyperplasia (ALH) and/or classic Lobular Carcinoma In Situ according to the WHO Classification of Tumours of the Breast, is no reason to exclude, whereas pleomorphic LCIS is
- Symptomatic DCIS e.g. DCIS detected by palpation or bloody nipple discharge
- Synchronous invasive carcinoma in the contralateral breast
- Prior history of invasive breast cancer or DCIS, prior surgery because of benign breast lesion (s) is allowed
- Prior history of other malignancy (except non-melanoma skin cancer and carcinoma in situ of the cervix) unless patient is discharged from follow-up for at least five years.
- Serious disease that precludes definitive surgical treatment (e.g cardiovascular/ pulmonary/ renal disease)
- Individual with a family member with a known gene mutation associated with increased risk of breast cancer, unless study participant is a proven non-carrier of mutation
- Pregnancy or breast-feeding. Contraceptive measures during the trial are mandatory for those patients that will participate in standard treatment arm and adequate counseling should be provided by the treating physician. The duration of contraception will be specified by the treating physician according to patient and treatment characteristics, standard clinical practice and national regulations
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (60)
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, Netherlands
Noordwest Ziekenhuisgroep- site Alkmaar
Alkmaar, Netherlands
Flevoziekenhuis
Almere Stad, Netherlands
Onze Lieve Vrouwe Gasthuis
Amsterdam, Netherlands
The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
Amsterdam, Netherlands
Rijnstate Ziekenhuis
Arnhem, Netherlands
Wilhelmina Ziekenhuis Assen
Assen, Netherlands
Rode Kruis Ziekenhuis
Beverwijk, Netherlands
Alexander Monro Ziekenhuis
Bilthoven, Netherlands
Amphia Ziekenhuis
Breda, Netherlands
Reinier de Graaf Gasthuis
Delft, Netherlands
Deventer Ziekenhuis
Deventer, Netherlands
Slingeland Ziekenhuis
Doetinchem, Netherlands
Albert Schweitzer Ziekenhuis
Dordrecht, Netherlands
Ziekenhuis Gelderse Vallei
Ede, Netherlands
Catharina Ziekenhuis
Eindhoven, Netherlands
Maxima Medisch Centrum
Eindhoven, Netherlands
Medisch Spectrum Twente Ariensplain
Enschede, Netherlands
Groene Hart Ziekenhuis
Gouda, Netherlands
Martini Ziekenhuis
Groningen, Netherlands
Universitair Medisch Centrum Groningen
Groningen, Netherlands
Spaarne Gasthuis
Haarlem, Netherlands
Saxenburgh Medisch Centrum
Hardenberg, Netherlands
Ziekenhuis St. Jansdal
Harderwijk, Netherlands
Tjongerschans Ziekenhuis
Heerenveen, Netherlands
Zuyderland Medisch Centrum
Heerlen, Netherlands
Ziekenhuisgroep Twente
Hengelo, Netherlands
Ter Gooi
Hilversum, Netherlands
Spaarne ziekenhuis
Hoofddorp, Netherlands
Treant Zorggroep Bethesda
Hoogeveen, Netherlands
Dijklander
Hoorn, Netherlands
Medisch Centrum Leeuwarden
Leeuwarden, Netherlands
Leids Universitair Medisch Centrum
Leiden, Netherlands
Alrijne Ziekenhuis
Leiderdorp, Netherlands
Haaglanden MC Antoniushove
Leidschendam, Netherlands
Academisch Ziekenhuis Maastricht
Maastricht, Netherlands
St. Antonius Ziekenhuis
Nieuwegein, Netherlands
Canisius-Wilhelmina Ziekenhuis
Nijmegen, Netherlands
Dijklander
Purmerend, Netherlands
Erasmus Medisch Centrum
Rotterdam, Netherlands
Maasstad Ziekenhuis
Rotterdam, Netherlands
Franciscus Gasthuis en Vlietland
Schiedam, Netherlands
Zuyderland Ziekenhuis
Sittard, Netherlands
Antonius Ziekenhuis
Sneek, Netherlands
Zorgsaam Zeeuws-Vlaanderen
Terneuzen, Netherlands
Zorgsaam Ziekenhuis
Terneuzen, Netherlands
HagaZiekenhuis
The Hague, Netherlands
Ziekenhuis Rivierenland
Tiel, Netherlands
St. Elisabeth Ziekenhuis
Tilburg, Netherlands
Bernhoven Ziekenhuis
Uden, Netherlands
Diakonessenhuis
Utrecht, Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, Netherlands
Maxima Medisch Centrum - Locatie Veldhoven
Veldhoven, Netherlands
VieCuri - Medisch Centrum voor Noord-Limburg - Locatie Venlo
Venlo, Netherlands
St Jans Gasthuis
Weert, Netherlands
Streekziekenhuis Koningin Beatrix
Winterswijk, Netherlands
Zaans Medisch Centrum
Zaandam, Netherlands
Haga ziekenhuis loc Zoetermeer
Zoetermeer, Netherlands
Gelre ziekenhuizen
Zutphen, Netherlands
Isala Klinieken
Zwolle, Netherlands
Related Publications (1)
Elshof LE, Tryfonidis K, Slaets L, van Leeuwen-Stok AE, Skinner VP, Dif N, Pijnappel RM, Bijker N, Rutgers EJ, Wesseling J. Feasibility of a prospective, randomised, open-label, international multicentre, phase III, non-inferiority trial to assess the safety of active surveillance for low risk ductal carcinoma in situ - The LORD study. Eur J Cancer. 2015 Aug;51(12):1497-510. doi: 10.1016/j.ejca.2015.05.008. Epub 2015 May 26.
PMID: 26025767BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jelle Wesseling, PhD
The Netherlands Cancer Institute
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 24, 2015
First Posted
July 8, 2015
Study Start
February 13, 2017
Primary Completion (Estimated)
February 1, 2034
Study Completion (Estimated)
February 1, 2034
Last Updated
January 26, 2026
Record last verified: 2025-01
Data Sharing
- IPD Sharing
- Will not share