Studies Show Chest Radiation in Childhood Cancer Survivors Conferred Breast Cancer Risk Equal to BRCA1/2 Carriers

Even low doses of chest radiation from 10 to 19 Gy increased risk for secondary cancers in the breast

The cumulative incidence of breast cancer by age 50 found in childhood Hodgkin lymphoma survivors who received chest radiation was equal to that of women who are BRCA1 mutation carriers, according to the results of a study that looked at data from the Childhood Cancer Survivor Study and the Women’s Environmental Cancer and Radiation Epidemiology (WECARE) Study. The breast cancer risk among survivors of other childhood cancers who received chest radiation was also significantly increased, equivalent to that of BRCA2 mutation carriers (Fig. 1).

“People know that risk of breast cancer increases with increasing radiation dose and, therefore, people who are treated with moderate to high doses of radiation are getting screened annually,” said Chaya S. Moskowitz, PhD, of Memorial Sloan-Kettering Cancer Center, during Monday’s Pediatric Oncology II Oral Abstract Session (Abstract CRA9513).

“However, we also found that there is increased risk for breast cancer in women treated with lower doses of radiation as well.”

In the study, Dr. Moskowitz and colleagues at 26 institutions in North America examined 1,286 females treated with chest radiation for cancer who were younger than age 21 at diagnosis between 1970 and 1986. All participants had to have survived at least 5 years.

Fifty-three percent of participants had childhood Hodgkin lymphoma.

The cumulative incidence of breast cancer in BRCA1/2 mutation carriers was estimated using 4,570 female firstdegree relatives of 1,397 women with unilateral breast cancer in the WECARE study. These two groups were then compared with rates of breast cancer in the general public taken from Surveillance, Epidemiology, and End Results (SEER) data.

Participants were followed for a median of 26 years. During that time, 176 women were diagnosed with breast cancer, 147 of whom had had Hodgkin lymphoma.

The overall cumulative incidence for breast cancer by age 50 for the cohort was 24%; it was 30% for Hodgkin lymphoma survivors. When looking at BRCA carriers, the cumulative incidence was 31% among BRCA1 carriers and 10% among BRCA2 carriers.

Even Lower Doses Increase Risk

When the researchers looked at the cumulative incidence of breast cancer by radiation dose, they found that even among those children thought to have received a low radiation dose of 10 to 19 Gy, there was a substantially increased risk for secondary breast cancers (Fig. 2).

The Children’s Oncology Group recommends that childhood cancer survivors who received 20 Gy or more of radiation to the chest area undergo semiannual clinical breast exams, annual mammograms, and annual breast MRI starting at either age 25 or 8 years after radiation.

“This important finding has implications for both surveillance recommendations for survivors, as well as [for] designing current treatment protocols, [because] we continue to use radiation doses of 15 to 21 Gy in contemporary treatment regimens for Hodgkin lymphoma,” said Discussant Maureen M. O’Brien, MD, MS, of Cincinnati Children’s Hospital Medical Center.

In addition, Dr. O’Brien told ASCO Daily News that improvements in screening compliance are needed even among the group of patients getting 20 Gy or more in chest radiation.

“There have been studies looking at what percentage of those patients are actually having surveillance done to catch these cancers early, and it ranges from 40% to 60%,” Dr. O’Brien said. Radiation Techniques Improving Dr. O’Brien pointed out that the results should be interpreted with some caution, as the cohort in the study, treated from 1970 to 1986, may not refl ect to most up-to-date radiotherapy techniques.

When Dr. Moskowitz and colleagues looked at the standardized incidence ratio (SIR) for breast cancer by radiation field, those patients who received whole lung radiation had higher ratios (SIR: 38.3; 95% CI: 23.1–63.4) than those patients who received mantle radiation (SIR: 23.7; 95% CI: 20.1–28.0) or other doses, defined as mediastinal/ involved field radiation therapy and hemithorax fields (SIR: 10.8; 95% CI: 6.8–17.1).

Regardless, Dr. O’Brien said that physicians have to do a better job with surveillance in this patient population.

“For patients [with childhood Hodgkin lymphoma] who have gotten more than 20 Gy to the chest, the rate of getting a breast cancer is the same as being a BRCA1 carrier,” Dr. O’Brien told ASCO Daily News.