A large international study published by Kunkler et al in The New England Journal of Medicine examined whether chest wall radiation therapy after mastectomy improves survival for patients with early-stage breast cancer. The study, known as the SUPREMO trial, found no overall survival difference between patients who received chest wall radiation and those who did not.
Below are key takeaways to help put the SUPREMO results in context and guide informed decisions about postmastectomy radiation therapy:
- All patients with lymph node-positive disease in SUPREMO underwent complete axillary dissection, not sentinel node biopsy.
- Modern postmastectomy radiotherapy is delivered to the chest wall and regional lymph nodes, not the chest wall alone, as was done in the SUPREMO study.
- Many patients in the SUPREMO study would not qualify for postmastectomy radiation using current guidelines, which likely explains why the benefit of radiation in this study was small.
ASTRO Response
While the headlines following its publication suggest that “radiotherapy can be avoided,” experts from the American Society for Radiation Oncology (ASTRO) emphasized that the findings do not change how most patients are treated today. The participants in SUPREMO were treated in an earlier era, between 2006 and 2013, with multidisciplinary approaches that differ substantially from current practice.
The key difference in how patients in the SUPREMO study were managed as compared to modern treatment is in how the lymph nodes were treated. In SUPREMO, all patients with positive lymph nodes had a full axillary dissection with removal of all lymph nodes in the axilla. Today, few patients undergo this type of lymph node surgery, because of studies showing no benefit to a more extensive lymph node surgery, and increased side effects as compared to radiation, such as the AMAROS study, published by Bartels et al in the Journal of Clinical Oncology in 2022. Another key difference is that in SUPREMO, radiation was directed to the chest wall, and very few patients received radiation to the supraclavicular and/or internal mammary lymph nodes. Modern postmastectomy radiotherapy for patients with positive lymph nodes, in contrast, includes treatment of these lymph nodes, and much of the benefit of radiation is driven by lymph node treatment.
Another factor that limits our ability to apply the findings from the SUPREMO study to patients today is the heterogeneity of the patients included, with a substantial proportion of patients in the trial population who would not meet criteria for postmastectomy radiation today, such as the 25% of patients with lymph node–negative tumors and 41% with a single micro- or macrometastatic lymph node. The patient population in the study demonstrated a low baseline risk, with only 3% of patients developing chest wall recurrence without radiation. In such a low-risk cohort, we would not expect to see a large benefit of chest wall irradiation. Still, while there was no benefit of chest wall irradiation for patients with lymph node–negative disease, amongst patients with node-positive breast cancer, there was a significant reduction in locoregional recurrence. The SUPREMO authors’ suggestion that systemic therapy improvements alone reduced local recurrence is likely misattributed in the context of this low-risk patient population. Modern systemic therapy treatments are applied based on biological risk, and systemic treatment today is much more tailored than that used in the SUPREMO study.
Fortunately, an ongoing randomized study—the MA.39 study, also known as TAILOR RT (ClinicalTrials.gov identifier NCT03488693)—will provide a clearer picture of the benefit of postmastectomy radiation in the setting of modern treatment. In the MA.39 study, patients with low-volume lymph node–positive tumors are allowed to have sentinel node biopsy instead of axillary dissection. After mastectomy, patients with favorable tumor biology, defined by having an Oncotype score of ≤ 25, are randomly assigned to receive or not to receive radiation to the chest wall and regional lymph nodes. This study is still actively accruing, and the results will help determine if there is a subset of patients with lymph node–positive breast cancer who can forgo radiation to the chest wall and lymph nodes.
Even outside of this important study, modern radiation therapy today is far more precise and personalized than it was during the time the SUPREMO study evaluated. Today, each patient’s plan is shaped by their individual tumor features, risk factors, and preferences, and developed collaboratively by a multidisciplinary care team.
Ultimately, the results of the SUPREMO study apply to very few of our current patients, in whom sentinel lymph node, not axillary, dissection is best practice in most cases, and in whom systemic therapy decisions are driven by biologic risk and genomic assays. Outside of enrollment on the MA.39 study, postmastectomy radiation with regional nodal irradiation remains the standard of care for most patients with one to three positive nodes, as recommended in the ASTRO-ASCO-SSO postmastectomy radiotherapy guideline published in September of this year.
