Childhood chemotherapy linked to subsequent breast cancer risk among women
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Key takeaways:
- Women who received radiation and high-dose doxorubicin as a child had the greatest risk for subsequent breast cancer.
- Nearly 5% of girls receiving anthracycline-based chemotherapy had subsequent breast cancer.
Women who received anthracycline chemotherapy following a childhood cancer diagnosis are at an increased risk for subsequent breast cancer later in life, according to data published in Nature Medicine.
Women treated with high-dose doxorubicin, but without radiation to the chest, have nearly a six-fold greater risk for breast cancer before the age of 40 than women in the general population, researchers wrote.
“We have known for some time that anthracyclines can be harmful to the heart, so the importance of keeping the dose of this type of chemotherapy low was already clear,” Yuehan Wang, MSc, a member of the Kremer group and a PhD student at the Princess Máxima Center for Pediatric Oncology, said in a press release.
“Developing a second cancer is a rare but serious late effect of childhood cancer treatment,” she added. “Our results underline the need to reduce the dose of doxorubicin in children whenever possible.”
Background and methodology
Anthracycline-based chemotherapy is associated with increased subsequent breast cancer risk among female childhood cancer survivors, but current evidence lacks sufficient data to support potential early breast cancer screening recommendations for this potential patient population.
Researchers pooled individual patient data of 17,903 childhood cancer survivors (median age at diagnosis, 6.7 years; interquartile range, 2.8–13.0) from six studies to analyze dose-dependent effects of individual anthracycline agents on developing subsequent breast cancer and interactions with chest radiotherapy.
Results, next steps
Of the patient population, 782 (4.4%) developed breast cancer later in life.
Researchers noted a dose-dependent increased subsequent breast cancer risk for doxorubicin (HR per 100 mg m2 = 1.24; 95% CI: 1.18–1.31), with a more than twofold increased risk for survivors treated with a 200 mg m2 or greater cumulative doxorubicin dose vs. no doxorubicin (HR = 2.5 for 200–299 mg m2; HR = 2.33 for 300–399 mg m2; and HR = 2.78 for 400 mg m2).
For daunorubicin, associations did not appear statistically significant; however, researchers observed an association between epirubicin and increased subsequent breast cancer risk (HR = 3.25, 95% CI: 1.59–6.63).
Patients treated with doxorubicin and chest irradiation had an HR per 100 mg m2 of 1.11 (95% CI: 1.02–1.21) vs. 1.26 (95% CI: 1.17–1.36) for those who did not receive irradiation.
The findings support the early initiation of breast cancer surveillance for childhood cancer survivors who received a 200 mg m–2 or greater cumulative doxorubicin dose, the investigators said.
“Doxorubicin is associated with a dose-dependent increase of [subsequent breast cancer], both in women treated with and without chest radiotherapy,” Wang and colleagues wrote. “We believe that the results of our study should be considered in updates of the [breast cancer] surveillance guidelines for survivors and can inform future treatment protocols for newly diagnosed childhood cancer patients.”
References:
- Higher breast cancer risk after certain forms of childhood cancer treatment (press release). Available at: https://www.eurekalert.org/news-releases/1001051. Published Sept. 11, 2023. Accessed Sept. 17, 2023.
- Wang Y, et al. Nat Med. 2023;doi:10.1038/s41591-023-02514-1.
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Wang Y, et al. Nat Med. 2023;doi:10.1038/s41591-023-02514-1.
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