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Increased Risk of Treatment-related Breast Cancer after Childhood Cancer

Combination Therapy may increase risk of breast cancer in childhood cancer survivors.

Combination radiotherapy and anthracycline chemotherapy for childhood cancer may elevate risk of secondary breast cancer among female patients compared to use of neither treatment, according to a study published October 28, 2019, in the journal JAMA Pediatrics.

Chemotherapy, especially anthracyclines, is being used more often to treat childhood cancers. Anthracyclines have been associated with cardiotoxicity and there is growing evidence that they can also increase the risk of breast cancer in childhood cancer survivors. This was the first study to evaluate risk from combined chemotherapy and radiotherapy in pediatric cancer patients. In the present treatment era, combined therapy is often used.

In this case-control study of 271 patients with breast cancer within the North America Childhood Cancer Survivor Study, the largest of its kind, investigators found the combination of anthracyclines and radiation doses to the breast was associated with increased breast cancer risks and was greater than the sum of their effects, consistent with an additive interaction.

Overall risk for breast cancer increased with both increasing radiation dose and increasing cumulative anthracycline dose. The radiation dose-response was similar for ER+ and ER- breast cancers, whereas a slightly higher anthracycline dose response was observed in ER+, compared to ER- tumors, which warrants further investigation. Additionally, high radiation doses to the ovaries resulted in a much lower risk of both ER+ and ER- invasive breast cancers. 

Though radiation doses for many childhood cancers have been lowered and target fields narrowed over the last few decades, investigators have not seen a commensurate decrease in treatment-related breast cancer rates. These results suggest that the addition of anthracycline therapy may contribute to the observed increase in breast cancer risk.

Veiga LH et al. Association of Breast Cancer Risk After Childhood Cancer With Radiation Dose to the Breast and Anthracycline Use. JAMA Pediatrics, October 2019. DOI:10.1001/jamapediatrics.2019.3807.  [Epub ahead of print]

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