Patients with invasive breast cancer who had low scores on an investigational gene molecular signature had similar rates of local recurrence independent of whether they received adjuvant radiation therapy after breast-conserving surgery, according to findings presented by Karlsson et al at the 2022 San Antonio Breast Cancer Symposium (Abstract GS4-03).
Patients with breast cancer who undergo breast-conserving surgery may be recommended to receive adjuvant radiation therapy to reduce the risk of local recurrence.
“However, many patients will not experience a local recurrence even without radiation therapy,” explained presenting author Per Karlsson, MD, Professor of Oncology as well as senior consultant and Chief Physician in the Department of Oncology at the Sahlgrenska Comprehensive Cancer Center and the University of Gothenburg. “Currently, we do not have any reliable predictive classifiers to identify patients who might be able to skip radiation therapy. Since radiation therapy can be associated with problematic side effects in some patients, it is of clinical importance to identify those patients for whom radiation therapy can be safely omitted.”
In this study, Dr. Karlsson and his colleagues evaluated the predictive potential of POLAR (profile for the omission of local adjuvant radiotherapy) scores—an investigational 16-gene molecular signature that was developed based on gene-expression differences between patients with and without local recurrence after breast-conserving surgery. The genes included in the signature have been known to impact cellular proliferation and patients’ immune responses.
The researchers performed a meta-analysis of 623 patients with lymph node–negative, estrogen receptor–positive, HER2-negative breast cancer who were enrolled in one of three randomized clinical trials examining the efficacy of breast-conserving surgery with and without local breast radiation therapy.
To evaluate the predictive capability of POLAR, the researchers analyzed gene expressions in breast tumor samples, and each patient received a POLAR score. They then examined the impact of radiation therapy on patients with high and low POLAR scores.
Among the 429 patients with high POLAR scores, those who received adjuvant radiation therapy after breast-conserving surgery had a 63% reduction in local recurrence compared with those who did not receive adjuvant radiation therapy—suggesting the benefit of adjuvant radiation therapy for these patients.
In contrast, among the 194 patients with low POLAR scores, there were no significant differences in local recurrence rates between those who received adjuvant radiation therapy and those who did not. After 10 years, 5% of patients who received radiation therapy experienced a local recurrence, compared with 7% of those who did not receive radiation therapy.
“In a patient-level meta-analysis of three independent randomized clinical trials, the POLAR gene profile successfully predicted which patients would and would not benefit from local radiation therapy, thereby identifying a group of [patients with] breast cancer where radiation therapy may be safely omitted after breast-conserving surgery. Although only a minority of patients experience severe side effects to breast radiation, this adds up to a fair number of patients once you consider how prevalent breast cancer is,” Dr. Karlsson highlighted. “The POLAR gene profile may, therefore, help mitigate toxicities and improve quality of life for many patients.”
The researchers noted that the POLAR gene profile will need further validation and additional streamlining before it could be used in the clinic. Future research from Dr. Karlsson and his colleagues will examine whether the POLAR gene profile can also identify patients who may safely avoid regional radiation therapy—which may be associated with more severe toxicities than local radiation therapy.
A limitation of the study is its retrospective design. Additionally, the POLAR gene profile was developed using samples from patients who did not receive currently available endocrine therapies; however, validation trials included patients who received such therapies.
Disclosure: The research in this study was supported by funds from the Swedish Cancer Society, the Swedish Research Council, the King Gustaf V Jubilee Clinic Foundation, the ALF Agreement of the Swedish government, PFS Genomics, and Exact Sciences. Dr. Karlsson has pending patents with and receives royalties from Exact Sciences and PreludeDX.
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