Chest radiation in girls with Wilms tumor may increase breast cancer risk in adulthood

Girls who receive chest radiation for pulmonary metastases from Wilms tumor, a childhood kidney cancer, may be at higher risk for breast cancer later in life, a new study reports.

Guidelines from the Children's Oncology Group recommend routine early screening for breast cancer in childhood cancer survivors if they have received chest radiation at a dose of 20 Gy or greater. Most patients with Wilms tumor are not considered eligible for such screening because they would have received a lower radiation dose (12 to 14 Gy). Researchers used follow-up data from the National Wilms Tumor Studies 1 through 4 for 2,492 women from age 15 through mid-2013 to determine the rate of incident breast cancer in Wilms tumor survivors. Cumulative breast cancer risk at age 40, hazard ratios, and standardized incidence ratios compared to the U.S. population were calculated. The study results were published online Oct. 27 by Cancer.

The participants' median age was 27.3 years (interquartile range, 21.4 to 33.2 years; maximum age, 55.2 years) at last follow-up. Overall, 29 cases of metastatic breast cancer were diagnosed in 28 patients, 16 of 369 who had received chest radiation, 10 of 894 who had received only abdominal radiation, and 2 of 1,229 who had received no radiation. All but 4 cases occurred before age 40. Cumulative breast cancer risk at age 40 for these 3 groups was 14.8% (95% CI, 8.7% to 24.5%), 3.1% (9%% CI, 1.3% to 7.41%), and 0.3% (95% CI, 0.0% to 2.3%), respectively, while standardized incidence ratios were 27.6 (95% CI, 16.1 to 44.2) based on 5,010 person-years of follow-up, 6.0 (95% CI, 2.9 to 11.0) based on 13,185 person-years of follow-up, and 2.2 (95% CI, 0.3 to 7.8) based on 13,560 person-years of follow-up, respectively.

Women who were diagnosed with Wilms tumor at 10 years of age or younger were at high risk regardless of whether they received chest radiation; cumulative breast cancer risk at age 40 was 13.5% (95% CI, 5.6% to 30.6%), and the standardized incidence ratio was 23.6 (95% CI, 10.8 to 44.8) based on 1,463 person-years of follow-up.

The authors noted that their study was small and that patients who had had chest radiation might have been screened more aggressively for breast cancer later in life, among other limitations. However, they concluded that girls who survive Wilms tumor and were treated with chest radiation have a high risk of early breast cancer and are “strong candidates” for breast cancer surveillance before age 40.

“Current guidelines, which suggest yearly mammography and breast magnetic resonance imaging starting at age 25 years or 8 years after treatment culmination only for those who received ≥20 Gy of [radiation therapy] to the chest or mantle, would need to be revised to facilitate the early diagnosis and prompt treatment of [breast cancer] among survivors of [Wilms tumor],” the authors wrote.

The authors of an accompanying editorial called the risk for breast cancer among Wilms tumor survivors who had received chest radiation “substantial” and said that it emphasizes the need for both primary and secondary prevention in this population. Regarding the latter, they noted that if existing guidelines were expanded to include screening patients with radiation exposure of 10 to 19 Gy in addition to those with exposure of 20 Gy or over, all patients in the current study except 1 would have been screened before their breast cancer was diagnosed.

However, they also noted that recommended surveillance is often not performed in adult patients who have survived childhood cancer and stressed that oncologists must share information about breast cancer risk with patients and with their primary care physicians. In addition, they said, “Further research is needed to define the optimal imaging modality and to refine which survivors are the most appropriate candidates for surveillance.”