BACKGROUND AND PURPOSE:

• Intermediate-risk breast cancer refers to patients with stage II breast cancer and involvement of 1-3 axillary nodes or node negative with additional risk factors (e.g., larger tumor size, histologic grade 3 or lymphovascular invasion)
• Kunkler et al. (NEJM, 2025) investigated overall survival of postmastectomy radiotherapy selectively delivered to the chest wall in patients with intermediate-risk breast cancer

METHODS:

• International, phase 3, randomized trial
  • SUPREMO (Selective Use of Postoperative Radiotherapy after Mastectomy) trial
  • UK (125 sites) | Europe (25 sites in 7 countries) | Israel (1 site) | Turkey (1 site)
• Participants
  • Women with intermediate-risk breast cancer treated with mastectomy, an axillary procedure and systemic therapy
    • Stage pT1N1, pT2N1, or pT3N0 or
    • Stage pT2N0 with a histologic grade of 3, lymphovascular invasion, or both
• Interventions
  • Chest-wall irradiation (40 to 50 Gy)
  • No irradiation
• Study design
  • Analysis was by intention to treat
• Primary outcome
  • Overall survival at 10 years
• Secondary outcomes
  • Chest-wall recurrence
  • Regional recurrence
  • Disease-free survival
  • Distant metastasis-free survival
  • Cause of death
  • Radiation-related adverse events

RESULTS:

• Irradiation group: 808 participants | No irradiation group: 799 participants
  • Median follow-up: 9.6 years
• There was no significant difference in overall survival between the groups
  • Irradiation: 81.4% | No irradiation: 81.9%
  • Hazard ratio (HR) for death: 1.04 (95% CI, 0.82 to 1.30) | P=0.80
• There were fewer chest-well recurrences in the irradiation group
  • Irradiation: 1.1% | No irradiation: 2.5%
  • Between group difference <2 percentage points
  • HR 0.45 (95% Ci, 0.20 to 0.99)
• There was no difference in
  • Disease-free survival
    • Irradiation: 76.2% | No irradiation: 75.5%
    • HR for recurrence or death: 0.97 (95% CI, 0.79 to 1.18)
  • Distant metastasis-free survival
    • Irradiation: 78.2% | No irradiation: 79.2%
    • HR for distant metastasis or death: 1.06 (95% CI, 0.86 to 1.31)

CONCLUSION:

• For breast cancer patients with intermediate-risk of recurrence treated with mastectomy and contemporary adjuvant systemic therapy, radiotherapy of the chest wall did not improve overall survival rates
• The authors suggest that while local therapy supports better systemic treatment, current systemic therapies have passed the point where chest-wall irradiation adds benefit
• The authors state

We hope that our results stimulate a reevaluation of the evidence base for indications for chest-wall irradiation

Continuing to recommend chest-wall irradiation, in contexts in which evidence of benefit is marginal and the procedure is potentially detrimental, may divert limited resources from more effective treatments

Learn More – Primary Sources:

What is the Potential Effectiveness of Universal Screening for Germline Pathogenic Variants Among Women with Invasive Breast Cancer?