Anthracyclines, Radiation Have Additive Effect on Breast-Cancer Risk in Childhood-Cancer Survivors

By Reuters Staff

November 01, 2019

NEW YORK (Reuters Health) - Anthracyclines further increase breast-cancer risk in childhood-cancer survivors treated with chest irradiation, according to new findings.

"This study provides the first evidence to date that the combination of anthracyclines and radiotherapy may increase breast cancer risks compared with use of neither treatment with a similar radiation dose response for ER+ and ER- cancers and possibly higher anthracycline risks for ER+ cancers," Dr. Lene H. Veiga of the National Cancer Institute in Bethesda and colleagues write in JAMA Pediatrics, online October 28.

There is growing evidence that anthracyclines can increase future risk of breast cancer, regardless of whether the patient received radiotherapy to the chest, Dr. Veiga and her team note.

To investigate the risk based on radiation to the breasts and ovaries and anthracycline use, the authors performed a nested case-control study using data from the North American Childhood Cancer Survivor Study, which includes more than 14,000 childhood cancers diagnosed in the U.S. and Canada in 1970-1986.

They matched 271 women diagnosed with breast cancer to 1,044 controls based on age at first cancer and follow-up duration.

The odds for developing breast cancer rose 3.9 times per 10 Gy of breast radiation, a significant increase, and it was also increased for doses below 5 Gy (OR, 1.7).

Patients who did not have irradiation of the ovaries, or received doses below 1 Gy, had a breast cancer OR of 6.8 per 10 Gy to the breast. Those who received doses of at least 15 Gy to the ovaries had a lower risk of radiation-associated breast cancer (OR, 1.4 per 10 Gy).

Breast-cancer risk increased as cumulative anthracycline dose increased (OR, 1.23 per 100 mg/m2), with a somewhat stronger effect for ER-positive cancers compared to ER-negative tumors (OR 1.49 vs. 1.10, respectively).

The OR for breast cancer for patients who received anthracyclines and at least 10 Gy of breast radiation was 19.1, compared to 9.6 for patients who received less than 1 Gy of breast radiation and were not on anthracyclines.

"The results suggest that the combination of anthracyclines and even moderate radiation doses to the breast (>=10 Gy) can increase breast cancer risks," Dr. Veiga and colleagues write. "Our results may help inform risk management for patients with childhood cancer treated in the past, as well as potential breast cancer risk associated with current treatment protocols."


JAMA Pediatr 2019.