Radiotherapy Omission in Low Risk Ductal in Situ Carcinoma Breast

NCT ID: NCT03878342

Last Updated: 2026-01-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

295 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-05-10

Study Completion Date

2034-11-14

Brief Summary

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Following breast-conserving surgery (BCS) for localized ductal carcinoma in situ (DCIS) of the breast, whole-breast irradiation (WBRT) is a standard of care, reducing the absolute rate of in-breast recurrences (IBR) by more than 15% at 10 years, from 28% without radiotherapy to 13 % with radiotherapy. Half of the recurrences occurred as invasive disease. Whereas in the comparative trials, WBRT did not impact on overall survival, survival of patients who recurred with invasive cancers was impaired in comparison to patients who did not recur, or to patients with DCIS-only recurrences.

Using criteria based on age, tumor size, nuclear grade, and margins status, several trials and cohort studies failed to identify subgroups of patients at low risk, who could be safely spared the need for WBRT. The Radiation Therapy Oncology Group (RTOG) DCIS trial included patients treated with BCS for low- or intermediate grade DCIS revealed by unifocal microcalcifications, size ≤25 mm, margins ≥3 mm, and no residual microcalcifications after surgery. The 5-year rates of IBR were 3.5 % without radiotherapy, versus 0.4 % with radiotherapy, and 6.7 % and 0.9 % at 7 years, respectively (p \<0.001). Sixty percent of the patients received tamoxifen in both groups.

Several studies showed that the same molecular classes were identified in DCIS as in invasive cancers. Studies suggested that low proliferation, hormone receptors expression, and lack of ERBB2 amplification were associated with a low risk of IBR in patients not receiving radiotherapy. A combined signature was tested in the Eastern Cooperative Oncology Group (ECOG) trial, showing a 10% IBR rate at ten years in patients with a low-risk.

Identifying very low-risk DCIS, using biological markers in addition to the clinical and histological markers of low-risk DCIS, could help to select patients who could be safely avoided WBRT following BCS. It would avoid over-treatment in these women and could decrease the cost of management.

Detailed Description

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Conditions

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DCIS Breast Cancer Low Risk DCIS Breast Conserving Surgery Radiotherapy Omission

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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No Radiotherapy

No Irradiation- Active surveillance

Group Type EXPERIMENTAL

No Radiotherapy

Intervention Type OTHER

No Irradiation- Active surveillance

Radiotherapy

two fractionation regimens will be allowed for whole-breast irradiation: 50 Gy in 25 fractions over 5 weeks or 40 Gy in 15 fractions over 3 weeks. The delivery of an additional dose to the tumour bed (boost) will be at the referring physician discretion, according to the guidelines

Group Type ACTIVE_COMPARATOR

Radiotherapy

Intervention Type RADIATION

two fractionation regimens will be allowed for whole-breast irradiation: 50 Gy in 25 fractions over 5 weeks or 40 Gy in 15 fractions over 3 weeks. The delivery of an additional dose to the tumour bed (boost) will be at the referring physician discretion, according to the guidelines

Interventions

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Radiotherapy

two fractionation regimens will be allowed for whole-breast irradiation: 50 Gy in 25 fractions over 5 weeks or 40 Gy in 15 fractions over 3 weeks. The delivery of an additional dose to the tumour bed (boost) will be at the referring physician discretion, according to the guidelines

Intervention Type RADIATION

No Radiotherapy

No Irradiation- Active surveillance

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Woman aged ≥50 years,
2. ECOG performance status ≤2
3. Microcalcifications on pre-biopsy mammography, unifocal, ≤25 mm or opacity without microcalcifications and no clinical palpable tumour
4. Absence of suspicious residual microcalcifications either on post-biopsy/ preoperative localization mammography, or on post-operative mammography Note: if absence of residual microcalcifications on post-biopsy/pre-operative mammography, post-operative mammography is not mandatory;
5. Breast-conserving surgical excision;
6. Histologically proven DCIS of the breast without an invasive component; Note Incidental histological finding of DCIS lesions developed within a benign breast lesion as well as an association with classical lobular carcinoma in situ (LCIS) associated with the DCIS are accepted.
7. Free margins (≥2 mm), or free margins following re-excision;
8. Low or Intermediate nuclear grade; Note: In case of nuclear grade heterogeneity within the same sample or between the biopsy or the surgical specimen, the highest nuclear grade score will prevail.
9. Tumour tissue sample availability; Note: Surgical specimen is mandatory unless no residual disease on the surgical specimen. In this instance, the initial diagnosis biopsy is required.
10. Absence of extensive necrosis (≤30% of the lumen diameter);
11. Immunohistochemical characteristics of luminal A subtype: ER≥10 %, PR ≥20 %, HER2 negative (0/1+) or 2+ not amplified (confirmed by fluorescent in situ hybridization (FISH) or chromogenic in situ hybridization (CISH)), Ki67 \<15%.
12. Patient willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled visits and examinations and including follow-up;
13. Written informed consent.
14. Affiliation to the French social security.

Exclusion Criteria

1. Endocrine treatment for breast cancer.
2. Previous invasive breast cancer including contralateral breast cancer, either metachronous or synchronous
3. Previous DCIS except contralateral DCIS in complete and continuous remission for more than 5 years
4. Previous other cancers (except basal-cell, carcinoma in situ of the cervix or endometrium), not in complete and continuous remission for more than 10 years
5. Known breast-cancer predisposing germ-cell mutation;
6. Palpable tumour with a diagnosis of DCIS on biopsy
7. Bloody nipple discharge;
8. Histological size \>25 mm in one or multiple foci
9. High nuclear grade, including high nuclear grade in heterogeneous tumours;either on biopsy or on surgical specimen
10. Associated microinvasive or invasive component;
11. Presence of tumour cells in lymph nodes detected using H\&E or immunohistochemical examination (if lymph node sentinel biopsy or dissection has been performed);
12. Absolute contra-indication to whole-breast irradiation as determined by the referring physician;
13. Patient unable to comply with study obligations for geographic, social, or physical reasons, or who is unable to understand the purpose and procedures of the study.
14. Pregnant women or breast feeding mothers,
Minimum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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The French National Cancer Institute

UNKNOWN

Sponsor Role collaborator

UNICANCER

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alain FOURQUET, MD

Role: PRINCIPAL_INVESTIGATOR

Institut Curie

Locations

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Institut de Cancérologie de l'Ouest -Site Paul Papin

Angers, , France

Site Status

Institut Sainte Catherine

Avignon, , France

Site Status

Centre d'Oncologie et de Radiothérapie du Pays Basque

Bayonne, , France

Site Status

Clinique Belharra

Bayonne, , France

Site Status

Institut Bergonie

Bordeaux, , France

Site Status

Centre Francois Baclesse

Caen, , France

Site Status

Centre Hospitalier du Cotentin

Cherbourg, , France

Site Status

Centre Jean Perrin

Clermont-Ferrand, , France

Site Status

CHIC Créteil

Créteil, , France

Site Status

Hôpital Henri Mondor

Créteil, , France

Site Status

Centre Georges Francois Leclerc

Dijon, , France

Site Status

Centre Hospitalier De Lagny Sur Marne

Jossigny, , France

Site Status

CHU Saint-Pierre La Réunion

La Réunion, , France

Site Status

Centre Guillaume le Conquérant

Le Havre, , France

Site Status

Centre Oscar Lambret

Lille, , France

Site Status

Chu De Limoges - Hopital Dupuytren

Limoges, , France

Site Status

Centre Hospitalier Bretagne Sud

Lorient, , France

Site Status

Centre de Radiothérapie Mermoz

Lyon, , France

Site Status

Centre Léon Berard

Lyon, , France

Site Status

Hôpital La Croix Rousse

Lyon, , France

Site Status

Institut Regional Du Cancer Montpellier Val D Aurelle

Montpellier, , France

Site Status

Centre Azuréen De Cancérologie

Mougins, , France

Site Status

Centre Antoine Lacassagne

Nice, , France

Site Status

Centre de Haute Energie

Nice, , France

Site Status

Hopital Pitie Salpetriere

Paris, , France

Site Status

Institut CURIE

Paris, , France

Site Status

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status

Institut Jean Godinot

Reims, , France

Site Status

Centre Eugène Marquis

Rennes, , France

Site Status

Centre Frédéric Joliot

Rouen, , France

Site Status

Hôpital René Huguenin - Institut Curie

Saint-Cloud, , France

Site Status

CHU Saint-Etienne

Saint-Etienne, , France

Site Status

Centre De Radiothérapie De La Robertsau

Strasbourg, , France

Site Status

Centre Paul Strauss

Strasbourg, , France

Site Status

Institut Claudius Regaud

Toulouse, , France

Site Status

Institut De Cancerologie De Lorraine Alexis Vautrin

Vandœuvre-lès-Nancy, , France

Site Status

Gustave Roussy

Villejuif, , France

Site Status

Countries

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France

Other Identifiers

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UC-0107/1803

Identifier Type: -

Identifier Source: org_study_id

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