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Gene variants plus radiotherapy may up risk of contralateral breast cancer

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – Breast cancer patients with ATM missense variants who receive radiation therapy appear to be at increased risk for contralateral breast cancer, according to a report in the March 19th online issue of the Journal of the National Cancer Institute.

The ATM gene – ATM stands for “ataxia telangiectasia mutated” – regulates cellular responses to DNA damage from ionizing radiation.

Still, the authors emphasize that ATM variants are rare, and the current findings probably explain only a small portion of second primary breast malignancies.

To determine whether ATM variants play a key role in a radiation-induced contralateral breast cancer, Dr. Jonine L. Bernstein, from Memorial Sloan-Kettering Cancer Center, New York, and colleagues compared 708 women with contralateral breast cancer and 1397 matched controls with unilateral breast cancer. The data came from the Women’s Environmental, Cancer, and Radiation Epidemiology (WECARE) Study.

Overall, fewer than 1% of the women carried an ATM missense variant thought to be harmful. When these women received radiotherapy, their risk of contralateral breast cancer increased by 2.8- to 3.3-fold relative to women with wild-type ATM who did not have radiotherapy and by 5.3- to 5.8-fold relative to carriers of missense variant ATM who did not have radiotherapy.

In an editorial, Dr. David J. Brenner, from Columbia University Medical Center, New York, comments that the findings “reemphasize that we do not yet understand most of the etiology of the disturbingly high long-term risks of second breast cancers. It is important, therefore, to continue to seek prophylactic preventative options that are useful for all breast cancer survivors.”


J Natl Cancer Inst 2010;102:475-483.