In an analysis from the Childhood Cancer Survivor Study reported in JAMA Oncology, Tara O. Henderson, MD, MPH, and colleagues found that rates of invasive breast cancer have declined over time among female survivors of childhood cancer, with the reduction appearing to be largely associated with reductions in use of chest radiotherapy.
As stated by the investigators, “Breast cancer is the most common invasive subsequent malignant disease in childhood cancer survivors, though limited data exist on changes in breast cancer rates as primary cancer treatments have evolved.
Invasive breast cancer rates in childhood cancer survivors have declined with time, especially in those younger than 40 years. This appears largely associated with the reduced use of chest radiation therapy but was tempered by concurrent changes in other therapies.— Tara O. Henderson, MD, MPH, and colleagues
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Study Details
The retrospective cohort study included 5-year cancer survivors diagnosed before age 21 years between 1970 and 1999, with follow-up through December 2020. Changes in treatments were assessed by the decades: 1970s, 1980s, and 1990s. Changes in incidence of breast cancer were assessed by 5-year eras of primary diagnosis.
Key Findings
Among 11,550 survivors included in the analysis (median age = 34.2 years, range 5.6–66.8 years), 489 developed 583 breast cancers; of these, 427 were invasive and 156 were cases of ductal carcinoma in situ (DCIS). The median age at breast cancer diagnosis was 40.3 years (range = 19.9–62.1 years). The cumulative incidence of breast cancer was 8.1% (95% confidence interval [CI] = 7.3%–9.0%) by age 45 years. Risk of developing breast cancer was significantly greater among survivors compared with the general population matched for age, sex, and calendar year (standardized incidence ratio = 6.6, 95% CI = 6.1–7.2).
Changes in therapy by decade included reduced rates of chest radiotherapy (34% in the 1970s, 22% in the 1980s, and 17% in the 1990s) and pelvic radiotherapy (26%, 17%, and 13%, respectively) and increased rates of anthracycline exposure (30%, 51%, and 64%, respectively).
On multivariate analysis, significant increases in risk for invasive breast cancer were observed for chest radiotherapy vs no chest radiotherapy (relative rate [RR] = 8.44, P < .0001) and cumulative anthracycline dose of ≥ 250 mg/m2 with no chest radiotherapy (RR = 2.36, P < .001). No significant increases in risk were observed with lower anthracycline dose in patients with no chest radiotherapy or any exposure dose in patients with chest radiotherapy. A significantly reduced risk for invasive breast cancer was observed for pelvic radiotherapy vs no pelvic radiotherapy (RR = 0.62, P < .0001).
In analyses adjusting for age and age at diagnosis, the rate of invasive breast cancer decreased by 18% for each 5 years of primary cancer diagnosis era without accounting for treatments (RR = 0.82, 95% CI = 0.74–0.90). When accounting for chest radiotherapy, the rate declined by 11% every 5 years (RR = 0.89, 95% CI = 0.81–0.99). With further accounting for cumulative anthracycline dose and receipt of pelvic radiotherapy, the rate declined by 14% every 5 years (RR = 0.86, 95% CI = 0.77–0.96).
Standardized incidence ratios for DCIS generally increased over time, with no statistically significant changes in incidence.
The investigators concluded, “Invasive breast cancer rates in childhood cancer survivors have declined with time, especially in those younger than 40 years. This appears largely associated with the reduced use of chest radiation therapy but was tempered by concurrent changes in other therapies.”
Dr. Henderson, of the University of Chicago Comer Children’s Hospital, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.
