Invasive breast cancer rates decline over time among childhood cancer survivors
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Invasive breast cancer rates declined modestly during the past 30 years among childhood cancer survivors, according to study results published in JAMA Oncology.
The decrease appeared associated mostly with reductions in chest radiation therapy use, but concurrent changes in other cancer therapies slightly attenuated the decline, researchers noted.
Background and methods
“As childhood cancer treatment has become increasingly successful, researchers have identified significant long-term complications of therapy, including high rates of chronic health conditions and subsequent cancers,” Tara O. Henderson, MD, MPH, FASCO, Arthur and Marian Edelstein professor of pediatrics, section chief of pediatric hematology, oncology and stem cell transplantation, and chief of Chicagoland Children’s Health Alliance Cancer and Blood Disorders Service Line at The University of Chicago, told Healio.
“Breast cancer is one of the subsequent cancers that has elevated risk,” she continued. “Recognizing this risk and the association with exposures to chest radiation therapy, treatments for childhood cancer have been modified and early screening for breast cancer in survivors exposed to chest radiation therapy was initiated over the past few decades.”
Henderson and colleagues quantified the association between temporal changes in cancer treatment between 1970 and 1999 and subsequent risk for breast cancer among 11,550 female cancer survivors (median age, 34.2 years; range, 5.6-66.8) included in the Childhood Cancer Survivor Study. Survivors received a diagnosis before age 21 years and follow-up continued through Dec. 5, 2020.
Researchers used piecewise exponential models to estimate invasive breast cancer risk and ductal carcinoma in situ and the association with treatment exposure after adjusting for age at childhood cancer diagnosis and attained age.
Findings
Among all patients, 489 developed 583 breast cancers, including 427 invasive and 156 ductal carcinoma in situ.
Researchers reported a median time from primary cancer to breast cancer of 25.6 years (range, 6.7-47.4) and a median age at breast cancer diagnosis of 40.3 years (range, 19.9-62.1). Cumulative incidence of breast cancer increased from 1.6% (95% CI, 1.4-1.9) at age 35 years to 8.1% (95% CI, 7.3-9) by age 45 years.
Results also showed an increased risk for breast cancer among survivors when compared with the age, sex and calendar year-matched general population (standardized incidence ratio [SIR] = 6.6; 95% CI, 6.1-7.2).
Changes in cancer therapy by decade included a 34% decrease in chest radiotherapy use during the 1970s, followed by a 22% decrease in use during the 1980s and a 17% decrease during the 1990s. Researchers observed corresponding reductions in pelvic radiotherapy use, from 26% to 17% to 13%.
Conversely, researchers identified increased exposure to anthracycline chemotherapy, from 30% during the 1970s to 51% in the 1980s and 64% in the 1990s.
After adjustment for attained age and age at diagnosis, the rate of invasive breast cancer decreased by 18% for every 5 years of primary cancer diagnosis era (rate ratio [RR] = 0.82; 95% CI, 0.74-0.9). The decrease dropped to 11% (RR = 0.89; 95% CI, 0.81-0.99) every 5 years when accounting for chest radiotherapy exposure, but increased to 14% (RR = 0.86; 95% CI, 0.77-0.96) when adjusting for anthracycline dose and pelvic radiation therapy dose.
Researchers observed no statistically significant changes in ductal carcinoma in situ incidence, although SIRs tended to increase over time.
“We found that breast cancer risk has improved considering new approaches to and decreased use of radiotherapy, though modulated with increased use of anthracycline therapy,” Henderson said.
Implications
The findings suggest continued consideration of early screening for breast cancer among childhood cancer survivors is needed, along with consideration of individualized risk based on multiple exposures coupled with other risk factors, such as familial risk, Henderson said.
“Our treatment for pediatric cancer has continued to evolve after the year 2000,” she continued. “We need to continue to study breast cancer risk in survivors treated after 2000 to consider further changes in therapy, including novel treatments such as immunotherapy, and how these treatments impact breast cancer risk.”
The study showed the benefit of radiotherapy omission on the incidence of subsequent tumors after childhood cancer treatment, according to an accompanying editorial by Kelsey L. Corrigan, MD, MPH, and Michael Roth, MD, both researchers at The University of Texas MD Anderson Cancer Center.
“We are making progress in improving the long-term health and survival of childhood cancer survivors,” the editorial authors wrote. “However, patients with childhood cancer are still treated with radiotherapy and chemotherapy, as well as agents with unknown long-term adverse effects. Thus, much work remains.”
References :
- Corrigan KL, et al. JAMA Oncol. 2022;doi:10.1001/jamaoncol.2022.4590.
- Henderson TO, et al. JAMA Oncol. 2022;doi:10.1001/jamaoncol.2022.4649.
For more information:
Tara O. Henderson, MD, MPH, FASCO, can be reached at thenderson@peds.bsd.uchichago.edu.
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