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DCISLORDNCT02492607

Management of Low-risk (Grade I and II) DCIS

A study testing Standard treatment, digital mammography and radiotherapy in people with DCIS, run by The Netherlands Cancer Institute at 60 sites in Netherlands.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 45 years and older, women only
Conditions the study is for
DCIS
What is being tested?
Standard treatment, digital mammography and radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2,500 participants
Where
60 sitesNetherlands
Study dates
13 Feb 2017to 1 Feb 2034
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 45 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • The interval between histologic diagnosis of low-risk DCIS on biopsy and inclusion is ≤ 12 weeks

Who cannot join

  • 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
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  • 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

Trial locations and contacts

60 sites in 1 country.

60 sites in 1 country

Netherlands60 sites

  • Jeroen Bosch Ziekenhuis

    's-Hertogenbosch

  • Noordwest Ziekenhuisgroep- site Alkmaar

    Alkmaar

  • Flevoziekenhuis

    Almere Stad

  • Onze Lieve Vrouwe Gasthuis

    Amsterdam

  • The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis

    Amsterdam

  • Rijnstate Ziekenhuis

    Arnhem

  • Wilhelmina Ziekenhuis Assen

    Assen

  • Rode Kruis Ziekenhuis

    Beverwijk

  • Alexander Monro Ziekenhuis

    Bilthoven

  • Amphia Ziekenhuis

    Breda

  • Reinier de Graaf Gasthuis

    Delft

  • Deventer Ziekenhuis

    Deventer

  • Slingeland Ziekenhuis

    Doetinchem

  • Albert Schweitzer Ziekenhuis

    Dordrecht

  • Ziekenhuis Gelderse Vallei

    Ede

  • Catharina Ziekenhuis

    Eindhoven

  • Maxima Medisch Centrum

    Eindhoven

  • Medisch Spectrum Twente Ariensplain

    Enschede

  • Groene Hart Ziekenhuis

    Gouda

  • Martini Ziekenhuis

    Groningen

  • Universitair Medisch Centrum Groningen

    Groningen

  • Spaarne Gasthuis

    Haarlem

  • Saxenburgh Medisch Centrum

    Hardenberg

  • Ziekenhuis St. Jansdal

    Harderwijk

  • Tjongerschans Ziekenhuis

    Heerenveen

  • Zuyderland Medisch Centrum

    Heerlen

  • Ziekenhuisgroep Twente

    Hengelo

  • Ter Gooi

    Hilversum

  • Spaarne ziekenhuis

    Hoofddorp

  • Treant Zorggroep Bethesda

    Hoogeveen

  • Dijklander

    Hoorn

  • Medisch Centrum Leeuwarden

    Leeuwarden

  • Leids Universitair Medisch Centrum

    Leiden

  • Alrijne Ziekenhuis

    Leiderdorp

  • Haaglanden MC Antoniushove

    Leidschendam

  • Academisch Ziekenhuis Maastricht

    Maastricht

  • St. Antonius Ziekenhuis

    Nieuwegein

  • Canisius-Wilhelmina Ziekenhuis

    Nijmegen

  • Dijklander

    Purmerend

  • Erasmus Medisch Centrum

    Rotterdam

  • Maasstad Ziekenhuis

    Rotterdam

  • Franciscus Gasthuis en Vlietland

    Schiedam

  • Zuyderland Ziekenhuis

    Sittard

  • Antonius Ziekenhuis

    Sneek

  • Zorgsaam Zeeuws-Vlaanderen

    Terneuzen

  • Zorgsaam Ziekenhuis

    Terneuzen

  • HagaZiekenhuis

    The Hague

  • Ziekenhuis Rivierenland

    Tiel

  • St. Elisabeth Ziekenhuis

    Tilburg

  • Bernhoven Ziekenhuis

    Uden

  • Diakonessenhuis

    Utrecht

  • Universitair Medisch Centrum Utrecht

    Utrecht

  • Maxima Medisch Centrum - Locatie Veldhoven

    Veldhoven

  • VieCuri - Medisch Centrum voor Noord-Limburg - Locatie Venlo

    Venlo

  • St Jans Gasthuis

    Weert

  • Streekziekenhuis Koningin Beatrix

    Winterswijk

  • Zaans Medisch Centrum

    Zaandam

  • Haga ziekenhuis loc Zoetermeer

    Zoetermeer

  • Gelre ziekenhuizen

    Zutphen

  • Isala Klinieken

    Zwolle

Other trials in Netherlands

About this study

Official title: Management of Low Risk Ductal Carcinoma in Situ (Low-risk DCIS): a Non-randomized, Multicenter, Non-inferiority Trial; Standard Therapy Approach Versus Active Surveillance

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.

Read the detailed description

Background of the study:

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-risk DCIS (grade I and II DCIS) can safely be managed by active surveillance. If progression to invasive breast cancer would still occur, this will be lowgrade and hormone receptor positive with excellent survival rates. Also, breast-conserving treatment will still be an option, if no prior radiotherapy has been applied. It also may save many low-risk DCIS patients from intensive treatment.

Objective of the study:

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 and patient reported outcomes. To determine whether low- risk DCIS can safely (measured by ipsilateral invasive breast cancer rate at 10 years) be managed by an active surveillance strategy or if the conventional treatment, being either wide local excision (WLE) only, WLE plus radiotherapy or mastectomy, possibly followed by hormonal therapy, will remain the standard of care.

Study design:

Phase III, open-label, non-inferiority, multi-center, non-randomized clinical trial. By patient's preference, women will be included into one of the following arms: active surveillance or standard treatment according to local policy, being either WLE alone, WLE plus radiotherapy or mastectomy, possibly followed by hormonal therapy. The same follow-up scheme will be applied in both study arms, i.e. annual mammography for a period of five years and an additional two mammograms at year seven and ten.

Conditions
DCIS
Being tested
Standard treatment, digital mammography, radiotherapy
Keywords
Women, DCIS grade I and II, Active surveillance, Standard treatment
Medical subject headings
Carcinoma, Intraductal, Noninfiltrating

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Standard treatmentOther

    wide local excision only or wide local excision and radiotherapy or mastectomy.

    +/- hormonal therapy

  • digital mammographyDevice

    Also called Active surveillance

    annual mammography

  • radiotherapyRadiation

    according local policy

Study groups in NCT02492607
Study groupRoleWhat they receive
Standard treatmentActive 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.
Receives: Other: Standard treatment; Radiation: radiotherapy
Active surveillanceExperimentalActive surveillance : monitoring by annual digital mammography for a period of 5 years and a digital mammography at 7 and 10 years.
Receives: Device: digital mammography

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Ipsilateral invasive breast cancer-free rate at 10 years

    Ipsilateral invasive breast cancer-free rate at 10 years (both therapeutic policies

    Measured: 10 years from inclusion

Secondary outcomes (12)

  1. Rate of invasive disease at the final pathology specimen (standard arm only)

    Rate of invasive disease at the final pathology specimen (standard arm only)

    Measured: from inclusion till time of invasive disease during 10 years at minimum

  2. Rate of grade III DCIS at the final pathology specimen (standard arm only)

    Rate of grade III DCIS at the final pathology specimen (standard arm only)

    Measured: from inclusion till time of invasive disease during 10 years at minimum

  3. Biopsy rate for ipsilateral breast during follow-up

    Biopsy rate for ipsilateral breast during follow-up (both therapeutic policies)

    Measured: from inclusion to the time of death, during 10 years at minimum

  4. Masectomy rate for ipsilateral breast

    Masectomy rate for ipsilateral breast, baseline or subsequent ipsilateral DCIS or iBC (both therapeutic policies)

    Measured: from inclusion to the time of ipsilateral breast cancer or death, during 10 years at minimum

  5. Time to ipsilateral grade III DCIS

    Time to ipsilateral grade III DCIS, both therapeutic policies

    Measured: from inclusion to the development of a new ipsilateral DCIS of grade III, up to 10 years

  6. Time to contralateral DCIS

    Time to contralateral DCIS, both therapeutic policies

    Measured: from inclusion to the development of a new contralateral DCIS I,II,III, up to 10 years

  7. Time to contralateral invasive breast cancer

    Time to contralateral invasive breast cancer,, both therapeutic policies

    Measured: from inclusion to the development of a contralateral invasive breast cancer, up to 10 years

  8. Time to failure of active surveillance strategy

    Time to failure of active surveillance strategy, i.e. time to crossover to standard treatment, due to any cause

    Measured: from inclusion to the time patients received standard treatment to the ipsilateral breast, up to 10 years

  9. Distant metastases free interval

    Distant metastases free interval,both therapeutic policies

    Measured: from inclusion to the time of invasive distant metastases or death due to breast cancer, up to 10 years

  10. Overall survival

    Overall survival,both therapeutic policies

    Measured: from inclusion to the time of death, during 10 years at minimum

  11. Health Related Quality of life

    General QoL/global health perception, specific funcionalities, pain ( both therapeutic policies

    Measured: 6 times from inclusion to 10 yrs follow-up

  12. Cost-effectiveness

    Health economic evaluation (both therapeutic policies)

    Measured: 6 times from inclusion to 10 years follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jul 2015 (estimated)
  2. Study start13 Feb 2017
  3. Primary completion1 Feb 2034 (estimated)
  4. Study completion1 Feb 2034 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
2,500 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02492607
Sponsor's protocol ID
M18LORD
Other IDs
2014-04, EORTC-1401
Acronym
LORD
Status last verified
Jan 2025
First submitted
24 Jun 2015
Last updated
26 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 26025767

Questions about this trial

What is this clinical trial studying?

A study testing Standard treatment, digital mammography and radiotherapy in people with DCIS, run by The Netherlands Cancer Institute at 60 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 26 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 60 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ipsilateral invasive breast cancer-free rate at 10 years (time frame: 10 years from inclusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02492607, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2026.

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