The incidence of invasive breast cancer among childhood cancer survivors (CCSs) decreased from the 1970s to the 1990s, according to a study published in JAMA Oncology

This decrease was likely driven by a reduction in the use of chest radiation to treat pediatric cancer but was attenuated by an increase in the use of anthracycline treatment, researchers suggested. 

The researchers conducted this study to quantify the association between temporal changes in cancer treatment that took place from the 1970s to the 1990s and subsequent breast cancer risk in CCSs.

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The retrospective study included 11,550 female cancer survivors who were younger than 21 years of age when they were diagnosed between 1970 and 1999. Primary cancer diagnoses included leukemia (41%), central nervous system cancers (15%), Hodgkin (11%) and non-Hodgkin lymphoma (5%), Wilms tumor (9%), neuroblastoma (7%), bone cancer (7%), and soft tissue sarcoma (4%).

A total of 489 patients developed 583 breast cancers, including 427 cases of invasive breast cancer and 156 cases of ductal carcinoma in situ (DCIS). The cumulative incidence of breast cancer was 1.6% at 35 years of age, 8.1% at 45 years of age, and 18.1% at 55 years of age. 

CCSs had an increased risk of breast cancer when compared with a cohort from the general population that was matched for age, sex, and calendar year. The standardized incidence ratio (SIR) was 6.6 for all breast cancers, 6.1 for invasive breast cancer, and 8.5 for DCIS. The absolute excess risk (per 1000 person-years) was 1.8 for all breast cancers, 1.3 for invasive breast cancer, and 0.5 for DCIS. 

The researchers found that SIRs tended to decrease over time for invasive breast cancers diagnosed in CCSs at 39 years or younger. This trend was statistically significant for invasive breast cancers diagnosed before age 30. In this age group, the SIR for invasive breast cancer decreased from 17.3 in the 1970s to 6.9 in the 1980s and 7.0 in the 1990s (P =.01).

On the other hand, there were no significant changes in SIRs for DCIS in CCSs by decade, but SIRs were generally increasing over time. Among CCSs younger than 30 years old, for example, the SIR for DCIS decreased from 11.1 in the 1970s to 6.1 in the 1980s but rose to 17.7 in the 1990s (P =.05).

The researchers also looked at changes in therapy by decade. The use of chest radiation decreased from 34% in the 1970s to 22% in the 1980s and to 17% in the 1990s. The use of pelvic radiation decreased as well, from 26% to 17% to 13%. 

In contrast, the use of anthracyclines increased over the time periods studied, from 30% in the 1970s to 51% in the 1980s and to 64% in the 1990s. The proportion of patients with a cumulative anthracycline dose of 1-249 mg/m2 increased as well, from 11% to 32% to 51%.

The invasive breast cancer rate decreased 18% every 5 years of primary cancer diagnosis era (rate ratio [RR], 0.82; 95% CI, 0.74-0.90), when adjusting for patients’ attained age and age at diagnosis. When accounting for exposure to chest radiation, there was an 11% decrease every 5 years (RR, 0.89; 95% CI, 0.81-0.99). When the researchers adjusted for anthracycline dose and pelvic radiation exposure, there was a 14% decline every 5 years (RR, 0.86; 95% CI, 0.77-0.96).

“Invasive breast cancer rates in childhood cancer survivors have declined with time, especially in those younger than 40 years,” the researchers wrote. “This appears largely associated with the reduced use of chest radiation therapy, but was tempered by concurrent changes in other therapies.”

Disclosures: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Henderson TO, Liu Q, Turcotte LM, et al. Association of changes in cancer therapy over 3 decades with risk of subsequent breast cancer among female childhood cancer survivors: A report from the Childhood Cancer Survivor Study (CCSS). JAMA Oncol. Published online October 13, 2022. doi:10.1001/jamaoncol.2022.4649