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NCT Number: NCT03878342

Radiotherapy Omission in Low Risk Ductal in Situ Carcinoma Breast

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.

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Key information

Conditions

DCIS Adenocarcinoma Breast Cancer Breast Carcinoma In Situ Breast Conserving Surgery Breast Diseases Breast Neoplasms Carcinoma Carcinoma in Situ Carcinoma, Intraductal, Noninfiltrating Low Risk DCIS Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Ductal, Lobular, and Medullary Neoplasms, Glandular and Epithelial Radiotherapy Omission Skin Diseases Skin and Connective Tissue Diseases

Age range

50 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Institut de Cancérologie de l'Ouest -Site Paul Papin, Angers, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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,

Treatment and study plan

Radiotherapy

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

No Radiotherapy

Other

No Irradiation- Active surveillance

Primary outcomes

  1. 5-year cumulative incidence of in-breast cancer recurrences

    Time frame: 5 years

    Incidence of breast recurrence is determined from the date of last surgery to the date of breast recurrence.

Secondary outcomes

  1. Overall survival (OS)

    Time frame: 10 years

    OS is defined as the interval between the date of last surgery and the date of death from any cause;

  2. Breast cancer-specific survival (BCSS)

    Time frame: 10 years

    BCSS is defined as the interval between the date of last surgery and the date of death from breast cancer

  3. Relapse-free survival (RFS)

    Time frame: 10 years

    RFS is defined as the interval between the date of last surgery and the date of ipsilateral breast recurrence, regional nodes recurrence, distant metastases, of death from breast cancer, whichever occurs first

  4. Rate of in-breast recurrences (IBR).

    Time frame: 10 years

    In-breast recurrence defined as any carcinoma (invasive or in situ) occurring in the treated breast

  5. Rate of Contralateral breast

    Time frame: 10 years

    Contralateral breast cancer defined as any carcinoma (invasive or in situ) occurring in the contralateral breast.

  6. Quality of life of the patients using EORTC-QLQ-C 30

    Time frame: 3 years

    Quality of life will be assessed using QLQ-C 30 questionnaire from the European Organization for Research and Treatment of Cancer (EORTC). It is a 30-item self-reporting questionnaire developed to assess the quality of life of cancer patients. It is grouped into five functional subscales (role, physical, cognitive, emotional and social functioning). In addition, there are three multi-item symptom scales (fatigue, pain, and nausea and vomiting), individual questions concerning common symptoms in cancer patients,and two questions assessing overall Quality of Life

  7. Quality of life of the patients using EORTC-QLQ-BR23

    Time frame: 3 years

    Quality of Life of Patients will be assessed using a EORTC-QLQ BR23.It is a 23-item self-reporting specific questionnaire developed to assess the quality of life of breast cancer patients. It permits to evaluate the symptoms of breast cancer and the side effects of treatment.

  8. Cosmetics Evaluation

    Time frame: 3 years

    cosmetic results will be evaluated by centralized photographic analysis.

  9. Long term toxicities

    Time frame: Throughout study completion, up to 10 years.

    The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders and so the late effects and sequelea regarding the whole-breast radiotherapy.

Sponsors and collaborators

Lead sponsor

UNICANCER

Other

Collaborators

  • National Cancer Institute, France

Registry information

Official study title

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

Acronym: ROMANCE

Important dates

Study start
2019
Primary completion
2029
Study completion
2034
First posted
Mar 18, 2019
Registry last updated
Jan 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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