Depending on their treatment, childhood survivors of cancer may be more likely to have breast cancer in adulthood, a new retrospective study discovered. According to the report, the association lies in the use of combination anthracyclines and radiotherapy to treat the pediatric cancer.
“Chest irradiation for childhood cancer is associated with increases in breast cancer risk. Growing evidence suggests that anthracyclines increase this risk, but the outcome of combined anthracycline use and radiotherapy has not been studied,” the researchers stated. Their findings appeared in JAMA Pediatrics.
The study included 14,358 five-year survivors of childhood cancer who were diagnosed between 1970 and 1986 and followed through Dec. 31, 2016. Women who went on to develop breast cancer (cases, n = 271) were matched 4:1 to patients who did not develop breast cancer later in life (controls, n = 1,044) by age at first cancer and follow-up duration. Data collection including radiation dose to breast tumor site and ovaries and cumulative chemotherapy doses, which included anthracyclines and alkylating agents. The main outcome measure was the odds ratio (OR) for breast cancer in adulthood based on estrogen receptor (ER) status.
The median age at first cancer diagnosis in the case group was 15 (range, 3–20) years, and median age at breast cancer diagnosis was 39 (range, 20–57) years. Most (n = 201) of the breast cancers were invasive (ER positive [ER+], n = 113; ER negative [ER–], n = 41; unknown, n = 47), and the remaining 70 were situ breast cancers.
With every 10-Gy increase in radiation dose to the breast, the OR for breast cancer increased (OR per 10 Gy, 3.9; 95% CI, 2.5-6.5). ORs for breast cancer with increasing radiation doses were similar between ER+ (OR per 10 Gy, 5.5; 95% CI, 2.8-12.6) and ER– (OR per 10 Gy, 4.8; 95% CI, 1.7-22.3) cancers. The OR per 10-Gy increase to the breast, when compared to ovarian doses less than 1 Gy, was higher compared to women whose ovarian doses were 15 Gy or greater (6.8; 95% CI, 3.9-12.5 vs. 1.4; 95% CI, 1.0-6.4, respectively).
Increasing cumulative anthracycline dose was associated with a greater risk for breast cancer (OR per 100 mg/m2, 1.23; 95% CI, 1.09-1.39; P<0.01 for trend); the risk was higher for ER+ (OR per 100 mg/m2, 1.49; 95% CI, 1.21-1.83) than ER– (1.10; 95% CI, 0.84-1.45) cancers (P value for heterogeneity=0.47).
“There was an additive interaction between radiotherapy and anthracycline treatment (P = .04) with the OR for the combined association between anthracycline therapy and breast radiation dose of 10 Gy or more (compared with 0 to less than 1 Gy) of 19.1 (95% CI, 7.6-48.0) vs 9.6 (95% CI, 4.4-20.7) without anthracycline use,” the authors further reported.
The researchers concluded that the use of combination anthracyclines and radiotherapy to treat childhood cancers may be associated with a greater risk for breast cancer compared to using neither treatment; they stated that the findings may be useful in discussing guidelines for childhood survivors of cancer.