Female survivors of childhood cancer who have been treated with high doses of anthracyclines have a lifetime breast cancer risk similar to that of people with known hereditary breast cancer risk gene mutations, according to the findings of a recent study.1 Radiation to the chest area is already well established as a factor that increases the risk of breast cancers in survivors, but less is known about how anthracyclines contribute to this risk. Two previous studies, however, have suggested a link.2,3
The new research, which was published by researchers from St Jude Children’s Research Hospital in the Journal of Clinical Oncology, followed 1467 women enrolled in the St Jude Lifetime Cohort Study (SJLIFE) and found 68 breast cancers across 56 individuals (patients were a median age of 38.6 years). The study participants were all older than 18 years and were 10 or more years from diagnosis.
The study split up participants into 3 groups: those who had received no anthracyclines, those who had a total dose of the medication of under 249 mg/m2, and those who had a dose of 250 mg/m2 or higher. Survivors who had received the highest doses of anthracyclines had a cumulative incidence of breast cancer of 7% by age 35 years and 46% by age 50 years, similar to those who had received at least 10 Gy of chest radiation (cumulative risk of 8% and 41% by ages 35 years and 50 years, respectively).
“There have been a number of studies looking at breast cancer risk, and most have identified radiation as the predominant risk factor,” said Matthew Ehrdhart, MD, MS, lead author of the study and member of the Cancer Survivorship division at St Jude’s. “We observed a similar risk associated with anthracyclines across multiple statistical models that adjusted for other chemotherapy exposures, radiation, and genetic predisposition, and therefore, feel confident that anthracyclines uniquely contribute to breast cancer risk in childhood cancer survivors,” he added.
The researchers used a dose cutoff point of higher than 250 mg/m2 to define survivors who had received a high exposure to anthracyclines. What was the logic behind this figure, according to Dr Ehrhardt?
“If you look specifically at the study by Henderson and colleagues2 that previously demonstrated an anthracycline risk, that is, the threshold they used — which happens to be the same threshold associated with higher risk for cardiomyopathy. We don’t entirely understand the mechanism of anthracycline-mediated breast cancers; therefore, [we] decided to use this as a starting point,” noted Dr Ehrhardt.