Modern Therapies Challenge Radiation’s Role in Early Breast Cancer Survival

Findings from the international phase 3 SUPREMO trial (ISRCTN61145589) are reshaping how clinicians approach postmastectomy treatment for patients with intermediate-risk early breast cancer (eBC). The study found that omitting chest-wall irradiation in certain patients does not compromise survival outcomes when modern systemic therapies are used—signaling a potential shift in treatment paradigms toward pharmacologic optimization and collaborative care.¹

Study Overview

The SUPREMO trial enrolled 1607 women with intermediate-risk BC, defined as those with stage pT1N1, pT2N1, or pT3N0 disease, or stage pT2N0 with additional high-risk features such as histologic grade 3 or lymphovascular invasion. After mastectomy and axillary evaluation, all patients received systemic therapy and were randomized to undergo chest-wall irradiation (40–50 Gy) or no irradiation. The primary end point was overall survival (OS), assessed over a median follow-up of 9.6 years.²

Key Findings

At 10 years, OS was similar between the 2 groups: 81.4% in the irradiation group versus 81.9% in the no-irradiation group (hazard ratio [HR] for death, 1.04; 95% CI, 0.82–1.30; P=0.80). Chest-wall recurrence occurred in 1.1% of patients who received irradiation and 2.5% of those who did not—an absolute difference of less than 2 percentage points (HR, 0.45; 95% CI, 0.20–0.99).²

Disease-free survival and distant metastasis–free survival were nearly identical between groups (HR for recurrence or death, 0.97; 95% CI, 0.79–1.18; and HR for distant metastasis or death, 1.06; 95% CI, 0.86–1.31, respectively).²

A Shift in the Balance of Therapy

These findings show that the survival advantage once attributed to radiation may be diminishing for some patients. With the evolution of targeted therapies, endocrine agents, and immunomodulating regimens, the pharmacologic component of postmastectomy care now carries greater therapeutic weight.²

Rather than relying on radiation to achieve local control, clinicians can increasingly lean on the potency of systemic therapy to prevent both local and distant recurrence. This shift highlights a broader trend in oncology that invites pharmacists into a more central role in care delivery.

“We’ve now shown that with contemporary anti-cancer treatments, the risk of recurrence is very, very low—sufficiently low to avoid radiotherapy in most patients,” Ian Kunkler, MD, chief investigator of the international trial and a lead author of the paper, said in coverage by The New York Times.³

The Expanding Role of the Pharmacist

As chest-wall irradiation becomes less routine for certain patients, pharmacists are uniquely positioned to ensure the success of regimens that fill that therapeutic gap. Their expertise is critical in:

• Optimizing medication regimens: Collaborating with oncologists to individualize systemic therapy combinations and sequences that reduce recurrence risk.
• Managing adherence and persistence: Supporting long-term use of oral endocrine therapies and targeted agents, which are essential for maintaining disease control.
• Preventing and managing toxicities: Addressing adverse effects and drug–drug interactions that could compromise therapy effectiveness or adherence.
• Patient education: Empowering patients with knowledge about the rationale for de-escalated radiation and the importance of consistent pharmacologic therapy.

Clinical Implications

The SUPREMO trial demonstrates that, for many women with intermediate-risk eBC, omitting chest-wall irradiation does not reduce OS when effective systemic therapies are in place. This reinforces confidence in modern pharmacologic strategies and underscores the importance of multidisciplinary collaboration.

By redefining the balance between radiation and systemic therapy, the SUPREMO trial not only informs oncologic decision-making but also expands the scope of pharmacy practice in BC management.

REFERENCES

1. SUPREMO, an MRC Phase III randomised trial to assess the role of adjuvant chest wall irradiation in 'intermediate risk' operable breast cancer following mastectomy. ISRCTN. Updated January 2, 2024. Accessed November 6, 2025. https://www.isrctn.com/ISRCTN61145589

2. Kunkler I, Russell N, Anderson N, et al. Ten-year survival after postmastectomy chest-wall irradiation in breast cancer. N Engl J Med. November 5, 2025. DOI: 10.1056/NEJMoa2412225

3. Rabin RC. Radiation May Be Unnecessary for Many Breast Cancer Patients. The New York Times. November 6, 2025. Accessed November 6, 2025. https://www.nytimes.com/2025/11/05/health/breast-cancer-radiation.html?unlocked_article_code=1.zE8.iuDE.ubfJy9nSg3Oj&smid=url-share