Radiotherapy Omission in Low Risk Ductal in Situ Carcinoma Breast
ROMANCE
Prospective Study of Omission of Whole-breast Radiotherapy Following Breast-conserving Surgery in Patients With Very Low Risk Ductal Carcinoma in Situ of the Breast
1 other identifier
interventional
295
1 country
37
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started May 2019
Longer than P75 for not_applicable
37 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 14, 2019
CompletedFirst Posted
Study publicly available on registry
March 18, 2019
CompletedStudy Start
First participant enrolled
May 10, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 14, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 14, 2034
January 23, 2026
January 1, 2026
10.5 years
March 14, 2019
January 22, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
5-year cumulative incidence of in-breast cancer recurrences
Incidence of breast recurrence is determined from the date of last surgery to the date of breast recurrence.
5 years
Secondary Outcomes (9)
Overall survival (OS)
10 years
Breast cancer-specific survival (BCSS)
10 years
Relapse-free survival (RFS)
10 years
Rate of in-breast recurrences (IBR).
10 years
Rate of Contralateral breast
10 years
- +4 more secondary outcomes
Study Arms (2)
Radiotherapy
ACTIVE COMPARATORtwo 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
No Radiotherapy
EXPERIMENTALNo Irradiation- Active surveillance
Interventions
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
Eligibility Criteria
You may qualify if:
- Woman aged ≥50 years,
- ECOG performance status ≤2
- Microcalcifications on pre-biopsy mammography, unifocal, ≤25 mm or opacity without microcalcifications and no clinical palpable tumour
- 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;
- Breast-conserving surgical excision;
- 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.
- Free margins (≥2 mm), or free margins following re-excision;
- 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.
- 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.
- Absence of extensive necrosis (≤30% of the lumen diameter);
- 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%.
- 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;
- Written informed consent.
- Affiliation to the French social security.
You may not qualify if:
- Endocrine treatment for breast cancer.
- Previous invasive breast cancer including contralateral breast cancer, either metachronous or synchronous
- Previous DCIS except contralateral DCIS in complete and continuous remission for more than 5 years
- 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
- Known breast-cancer predisposing germ-cell mutation;
- Palpable tumour with a diagnosis of DCIS on biopsy
- Bloody nipple discharge;
- Histological size \>25 mm in one or multiple foci
- High nuclear grade, including high nuclear grade in heterogeneous tumours;either on biopsy or on surgical specimen
- Associated microinvasive or invasive component;
- Presence of tumour cells in lymph nodes detected using H\&E or immunohistochemical examination (if lymph node sentinel biopsy or dissection has been performed);
- Absolute contra-indication to whole-breast irradiation as determined by the referring physician;
- 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.
- Pregnant women or breast feeding mothers,
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- UNICANCERlead
- The French National Cancer Institutecollaborator
Study Sites (37)
Institut de Cancérologie de l'Ouest -Site Paul Papin
Angers, France
Institut Sainte Catherine
Avignon, France
Centre d'Oncologie et de Radiothérapie du Pays Basque
Bayonne, France
Clinique Belharra
Bayonne, France
Institut Bergonie
Bordeaux, France
Centre Francois Baclesse
Caen, France
Centre Hospitalier du Cotentin
Cherbourg, France
Centre Jean Perrin
Clermont-Ferrand, France
CHIC Créteil
Créteil, France
Hôpital Henri Mondor
Créteil, France
Centre Georges Francois Leclerc
Dijon, France
Centre Hospitalier De Lagny Sur Marne
Jossigny, France
CHU Saint-Pierre La Réunion
La Réunion, France
Centre Guillaume le Conquérant
Le Havre, France
Centre Oscar Lambret
Lille, France
Chu De Limoges - Hopital Dupuytren
Limoges, France
Centre Hospitalier Bretagne Sud
Lorient, France
Centre de Radiothérapie Mermoz
Lyon, France
Centre Léon Berard
Lyon, France
Hôpital La Croix Rousse
Lyon, France
Institut Regional Du Cancer Montpellier Val D Aurelle
Montpellier, France
Centre Azuréen De Cancérologie
Mougins, France
Centre Antoine Lacassagne
Nice, France
Centre de Haute Energie
Nice, France
Hopital Pitie Salpetriere
Paris, France
Institut CURIE
Paris, France
Centre Hospitalier Lyon Sud
Pierre-Bénite, France
Institut Jean Godinot
Reims, France
Centre Eugène Marquis
Rennes, France
Centre Frédéric Joliot
Rouen, France
Hôpital René Huguenin - Institut Curie
Saint-Cloud, France
CHU Saint-Etienne
Saint-Etienne, France
Centre De Radiothérapie De La Robertsau
Strasbourg, France
Centre Paul Strauss
Strasbourg, France
Institut Claudius Regaud
Toulouse, France
Institut De Cancerologie De Lorraine Alexis Vautrin
Vandœuvre-lès-Nancy, France
Gustave Roussy
Villejuif, France
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Alain FOURQUET, MD
Institut Curie
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- OTHER
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 14, 2019
First Posted
March 18, 2019
Study Start
May 10, 2019
Primary Completion (Estimated)
November 14, 2029
Study Completion (Estimated)
November 14, 2034
Last Updated
January 23, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will not share