Ireland
--:--IST
Active, not recruiting Not applicable

Radiotherapy Omission in Low Risk Ductal in Situ Carcinoma Breast

NCT03878342 · tracked via the Priya Life Science France tracker
Sponsor
Phase
Not applicable
Started
2019-05-10
Last updated
2026-01-23

Condition(s) studied

DCISBreast CancerLow Risk DCISBreast Conserving SurgeryRadiotherapy Omission

Investigational drug(s) / intervention(s)

RadiotherapyNo Radiotherapy

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

No Radiotherapy: No Irradiation- Active surveillance

Study 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.

Eligibility

Sex
FEMALE
Min age
50 Years
Max age
—
Healthy volunteers
No
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,

Primary outcome measure(s)

  • 5-year cumulative incidence of in-breast cancer recurrences — 5 years
    Incidence of breast recurrence is determined from the date of last surgery to the date of breast recurrence.

Trial sites (37)

FacilityCityRegionStatus
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
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT03878342 on ClinicalTrials.gov ↗ ← All trials in France