NCT04852887

De-Escalation of Breast Radiation Trial for Hormone Sensitive, HER-2 Negative, Oncotype Recurrence Score Less Than or Equal to 18 Breast Cancer (DEBRA)

A Phase III Clinical Trial Evaluating De-Escalation of Breast Radiation for Conservative Treatment of Stage I, Hormone Sensitive, HER-2 Negative, Oncotype Recurrence Score Less Than or Equal to 18 Breast Cancer

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,670 (estimated)
• Sponsor: NRG Oncology · Academic / Other
• Sex: All
• Age: 50 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This Phase III Trial evaluates whether breast conservation surgery and endocrine therapy results in a non-inferior rate of invasive or non-invasive ipsilateral breast tumor recurrence (IBTR) compared to breast conservation with breast radiation and endocrine therapy.

Detailed description

Breast conservation therapy for early stage breast cancer has been an important achievement of oncology practice in the last half century and breast radiotherapy (RT) has been essential in its development. Several seminal randomized clinical trials conducted in the 1980's era demonstrated that breast radiotherapy following lumpectomy yielded overall survival outcomes equivalent to mastectomy for treatment of early stage invasive breast cancer leading to the National Institute of Health (NIH) Consensus Conference statement in 1991 supporting breast conservation treatment.This established lumpectomy with RT as an alternative to mastectomy and subsequently the rate of breast conservation for eligible breast cancer patients rose steadily. Shortly thereafter, investigators recognized that the toxicity, patient burden, and geographic barriers associated with the protracted treatment course for breast RT was a potential barrier to breast conservation utilization. Numerous phase III clinical trials were conducted randomizing women post lumpectomy to RT vs. observation aimed at identifying which cases did not derive a significant RT benefit. No such subsets of breast cancer patients were consistently identified, thereby solidifying the standard that breast conservation required both lumpectomy and RT. Two meta-analyses by the Early Breast Cancer Trialists Collaborative Group (EBCTCG) in 2005 and 2011 further reinforced the value of breast RT post lumpectomy by examining the relationship of local recurrence and breast cancer mortality relative to the use of breast RT post lumpectomy. In each analysis, it found for axillary node negative breast cancer patients undergoing breast conservation a small but consistent increase in breast cancer mortality when breast radiotherapy was omitted. As a result, breast RT after lumpectomy has become an established paradigm for breast conservation for early stage breast cancer and is recommended by the NCCN 2018 guidelines (as it has for nearly two decades) that are commonly used today by clinicians and health systems alike. The landscape of early stage breast cancer has changed dramatically over the past three decades since the establishment of breast conservation. Widespread screening with mammography has led to the diagnosis of smaller and earlier stage disease. All breast cancers are now routinely characterized by their hormone sensitivity based on the presence of estrogen and progesterone receptors on tumor cells within the biopsy or surgical specimen and presence of HER2 (human epidermal growth factor receptor 2) which has provided an additional means of stratifying breast cancer into distinct prognostic groups. Small, node negative invasive breast cancer that is hormone sensitive (HS) and HER2-negative has a lower overall recurrence rate (local, regional, and distant) than breast cancers characterized by more adverse clinical pathologic features. However, other than in a smaller subset of women greater than 70 years old, clinical trials in this HS population still demonstrated unacceptable local recurrence risks long term after lumpectomy alone emphasizing that clinical and pathologic features are insufficient for consistently identifying when RT can safely be omitted.

Conditions

• Stage I Breast Cancer

Interventions

Type	Name	Description
OTHER	Radiation and Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane)	Post lumpectomy radiation therapy will be external beam radiation to either the whole breast + boost, partial breast irradiation, or Accelerated Partial Breast Irradiation that must begin within 12 weeks of the last breast cancer surgery(including re-excision of margins). Endocrine therapy for a minimum of 5 years. The specific regimen of endocrine therapy is at the treating physician's discretion. The dose and schedule of the drug(s) used for endocrine therapy should be consistent with the instructions in the drug package insert(s). Endocrine therapy may be initiated before, during, or after completion of radiation therapy at the discretion of the investigator.
DRUG	Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane)	Endocrine therapy for a minimum of 5 years. The specific regimen of endocrine therapy is at the treating physician's discretion. The dose and schedule of the drug(s) used for endocrine therapy should be consistent with the instructions in the drug package insert(s).

Timeline

• Start date: 2021-06-07
• Primary completion: 2031-04-08
• Completion: 2041-07-01
• First posted: 2021-04-21
• Last updated: 2026-04-15

Locations

832 sites across 4 countries: United States, Canada, Hong Kong, Japan