Molecular gene signature in study sheds light on adjuvant radiotherapy after breast-conserving surgery

Patients with invasive breast cancer who had low scores on an experimental molecular signature in a new study had similar rates of local recurrence whether or not they received adjuvant radiation therapy after breast-conserving surgery.

According to the results of a meta-analysis presented at the San Antonio Breast Cancer Symposium (SABCS), held December 6-10, “many patients will not experience local recurrence even without radiation therapy,” said Dr. Per Karlsson, professor of oncology at the University of Gothenburg in Sweden, said in a statement.

The findings have potential implications for breast cancer treatment, as breast cancer patients undergoing breast-conserving surgery are currently recommended to receive adjuvant radiation therapy to reduce the risk of local recurrence.

In the study, Karlsson and colleagues assessed the predictive potential of POLAR (Profile for the Omission of Local Adjuvant Radiotherapy), an experimental 16-gene molecular signature that was developed based on differences in gene expression between patients. with and without local recurrence after breast conservation. operation.

The genes included in the signature have known roles in cell proliferation and immune response.

Researchers performed a meta-analysis of 623 lymph node-negative, estrogen receptor-positive, and HER2-negative breast cancer patients who participated in one of three randomized clinical trials examining the effectiveness of breast-conserving surgery with and without local radiotherapy of the breast. therapy.

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

To assess the predictive ability of the 16-gene molecular signature, the researchers analyzed gene expression in breast tumor samples from patients and assigned each patient a score; they then looked at the impact of radiation therapy for patients with high and low scores. Among the 429 patients with high scores, those who received adjuvant radiotherapy after breast-conserving surgery had a 63% reduction in local recurrence compared to those who did not receive adjuvant radiotherapy, suggesting that adjuvant radiotherapy was beneficial for these patients.

In contrast, for the 194 patients with low scores, there was no significant difference in local recurrence rate between those who received adjuvant radiotherapy and those who did not. After 10 years, 5% of patients who received radiotherapy experienced local recurrence, compared to 7% of those who did not receive radiotherapy.

“Currently, we don’t have reliable predictive classifiers to identify patients who might be able to skip radiation therapy,” Karlsson said. “Because radiation therapy can be associated with problematic side effects in some patients, it is of clinical importance to identify patients for whom radiation therapy can be safely omitted.”

The “POLAR gene profile successfully predicted which patients would and would not benefit from local radiotherapy, thereby identifying a group of breast cancer patients where radiotherapy can be safely omitted after breast-conserving surgery” , Karlsson said, adding that genetic profiling can help mitigate toxicities and improve quality of life for many patients.

The POLAR gene profile will require further validation and streamlining before it can be used clinically, he noted.

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