Predictive classifier identifies patients who can skip radiation therapy

According to the findings of a meta-analysis proposed at the San Antonio Breast Cancer Symposium held on December 6–10^th, 2022, patients with invasive breast cancer who had low scores on an investigational gene molecular signature seemed to have similar rates of local recurrence regardless of whether they received adjuvant radiation therapy after breast-conserving surgery.

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Adjuvant radiation therapy is suggested for patients with breast cancer who have breast-conserving surgery to lower the chance of local recurrence.

However, many patients will not experience a local recurrence even without radiation therapy. 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.”

Per Karlsson MD, Professor, Oncology, Sahlgrenska Comprehensive Cancer Center

Per Karlsson is also associated with the University of Gothenburg in Sweden.

Karlsson and co-workers investigated the predictive ability of POLAR (Profile for the Omission of Local Adjuvant Radiotherapy), a 16-gene molecular profile generated based on gene expression differences between patients with and without local recurrence after breast-conserving surgery. The signature contains genes with recognized functions in immune response and cellular growth.

The efficacy of breast-conserving surgery with and without local breast radiation therapy was examined in three randomized clinical studies involving a total of 623 patients with lymph node-negative, estrogen receptor-positive, and HER2-negative breast cancer.

The Swedish SweBCG91RT trial, the Scottish Conservation Trial (SCT), and a trial from Canada’s Princess Margaret Hospital (PMH) were the clinical trials that were included in the meta-analysis. The meta-analysis included 623 patients, 354 from SweBCG91RT, 137 from SCT, and 132 from the PMH study.

To assess POLAR’s prognostic power, the researchers assessed gene expression in patient breast tumor samples to allocate each patient a POLAR score; they then looked into the effect of radiation therapy on patients with high and low POLAR scores.

Among the 429 patients with high POLAR scores, those who got adjuvant radiation therapy following breast-conserving surgery showed a 63% drop in local recurrence compared to those who did not, indicating that adjuvant radiation therapy was advantageous for these patients.

In contrast, there was no notable change in local recurrence rate between those who got adjuvant radiation therapy and those who did not for the 194 patients with low POLAR scores. After 10 years, 5% of radiation therapy patients reported a local recurrence, compared to 7% of those who did not get 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 breast cancer patients where radiation therapy may be safely omitted after breast-conserving surgery.

Per Karlsson MD, Professor, Oncology, Sahlgrenska Comprehensive Cancer Center

Karlsson added, “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. The POLAR gene profile may, therefore, help mitigate toxicities and improve quality of life for many patients.”

Karlsson stated that the POLAR gene profile will require additional validation and simplification before it can be used in the clinic.

Karlsson and coworkers’ future research will look into whether the POLAR gene profile may also be used to identify individuals who could safely evade regional radiation therapy, which is linked with more extreme toxicities than local radiation therapy.

The study’s retrospective nature is one of its limitations. Furthermore, the POLAR gene profile was created utilizing samples from patients who did not receive currently available endocrine therapies; nevertheless, patients who got such medications were included in the validation trials.