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Radiation Therapy Not Found to Increase Contralateral Breast Cancer Risk, Study Says

NEW YORK – A new study published this week in the Journal of the National Cancer Institute found that female breast cancer patients with germline mutations in ATM, BRCA 1/2, or CHEK2*1100delC were not at an increased risk for contralateral breast cancer following radiation treatment, suggesting that it would be unnecessary to modify therapy plans for patients under 55 years old with these alterations.

However, the study authors, led by Anne Reiner from Memorial Sloan Kettering Cancer Center, wrote in JNCI that they unexpectedly found that women with rare ATM missense variants of unknown significance had an increased risk for contralateral breast cancer after radiation therapy when compared to benchmark population risk data from the Surveillance, Epidemiology and End Results Program. This association should be explored further in future studies, they wrote.

Previously, it was unclear whether radiation therapy affected the risk of contralateral breast cancer in women who carried moderate-to-high penetrance pathogenic variants in ATM, BRCA1/2, and CHEK2*1100delC. Although radiation therapy has generally shown to improve breast cancer survival, an earlier study found that women treated with radiation therapy for their first primary breast cancer were at risk of developing contralateral breast cancer. Moreover, pathogenic variants hobbling normal functions of genes involved in repairing DNA damage have also been previously associated with increased risk of contralateral breast cancer.

In the present study, Reiner and colleagues aimed to measure the association between radiation therapy, pathogenic variants in the four genes, and contralateral breast cancer risk. The analysis involved 708 women with contralateral breast cancer and 1,399 women with unilateral breast cancer as controls. The researchers then calculated five- and ten-year cumulative risks of contralateral breast cancer based on whether these women received radiation therapy and their mutation status.

Women who harbored pathogenic BRCA1/2 variants had an increased contralateral breast cancer risk and a 10-year cumulative contralateral breast cancer risk of 19.3 percent, regardless of whether they were treated with radiotherapy. Women with likely pathogenic or pathogenic variants in ATM or CHEK2*1100delC also did not have a statistically significantly higher risk of contralateral breast cancer.

However, those with ATM rare missense VUS, which are currently not cancer-linked, and who received radiotherapy as their primary treatment had a slightly higher risk of contralateral breast cancer in this analysis. The team also found a non-statistically significant but slighter higher contralateral breast cancer risk for CHEK2*1100delC carriers treated with radiotherapy.

Reiner and coauthors concluded that "the increased radiation therapy-related risk for women with ATM rare missense VUS highlights the need for improved tools and approaches to resolve the functional impact of such variants, their interaction with radiation therapy, and subsequent contralateral breast cancer risk" and that "understanding the mechanism(s) of action of these ATM variants is necessary before this observation can inform clinical practice."