In a study reported in the Journal of Clinical Oncology, Sjöström et al identified a 16-gene signature—Profile for the Omission of Local Adjuvant Radiation, or POLAR—that predicted low likelihood of benefit from adjuvant radiotherapy in preventing locoregional recurrence in patients with node-negative, estrogen receptor–positive/HER2-negative breast cancer undergoing breast-conserving surgery.
As stated by the investigators, “Adjuvant radiotherapy is used for women with early-stage invasive breast cancer treated with breast-conserving surgery. However, some women with low risk of recurrence may safely be spared radiotherapy. This study aimed to identify these women using a molecular-based approach.”
Study Details
The study included an analysis of two trials that randomly assigned patients to receive radiotherapy or no radiotherapy following breast-conserving surgery: the SweBCG91-RT trial (stage I–II, no adjuvant systemic therapy) and the Princess Margaret trial (age ≥ 50 years, T1-T2, adjuvant tamoxifen). The SweBCG91-RT cohort was divided into training (n = 243) and validation (n = 354) cohorts; the Princess Margaret cohort (n = 132) was used as a validation cohort. Transcriptome-wide profiling was performed, and the 16-gene POLAR signature was trained to predict locoregional recurrence.
Key Findings
Among patients categorized as POLAR low-risk, the 10-year incidence of locoregional recurrence was 6% (95% confidence interval [CI] =2%–16%) without radiotherapy vs 5% (95% CI = 1%–13%) with radiotherapy in the SweBCG91-RT validation cohort, with no significant benefit of radiotherapy being observed (hazard ratio [HR] = 1.1, 95% CI = 0.39–3.4, P = .81). In the Princess Margaret validation cohort, the 10-year incidence was 7% (95% CI = 0%–27%) without radiotherapy vs 13% (95% CI = 2%–34%) with radiotherapy, with no significant benefit of radiotherapy being observed (HR = 1.5, 95% CI = 0.14–16.0, P = .74).
Among patients categorized as POLAR high-risk, the 10-year incidence of locoregional recurrence in the SweBCG91-RT cohort was 19% (95% CI = 13%–27%) without radiotherapy vs 8% (95% CI = 4%–14%) with radiotherapy, with a significant benefit of radiotherapy being observed (HR = 0.43, 95% CI = 0.24–0.78, P = .0055). In the Princess Margaret cohort, the 10-year incidence was 22% (95% CI = 10%–36%) without radiotherapy vs 8% (95% CI = 2%–20%) with radiotherapy, with a significant benefit of radiotherapy being observed (HR = 0.25, 95% CI = 0.07–0.92, P = .038).
The investigators concluded, “The novel POLAR genomic signature on the basis of locoregional recurrence biology may identify patients with a low risk of locoregional recurrence despite not receiving radiotherapy, and thus may be candidates for radiotherapy omission.”
Per Karlsson, MD, PhD, of the Department of Oncology, Sahlgrenska Comprehensive Cancer Center, Gothenburg, Sweden, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by The Swedish Breast Cancer Association, Swedish Cancer Society, and others. For full disclosures of the study authors, visit ascopubs.org.
