In a retrospective cohort study reported in The Lancet Oncology, Veiga et al found that receipt of radiotherapy was the strongest risk factor for development of thoracic soft-tissue sarcomas in U.S. breast cancer survivors; both hypertension and diabetes were significant risk factors for angiosarcoma.
As stated by the investigators, “Soft-tissue sarcoma is a rare but serious side effect of radiotherapy to treat breast cancer, and rates are increasing in the United States. We evaluated potential co-factors in two complementary cohorts of U.S. breast cancer survivors.”
Study Details
The study involved data from 15,940 patients diagnosed with breast cancer from January 1990 to December 2016 in Kaiser Permanente (KP) Colorado, KP Northwest, and KP Washington (KP cohort) and 457,300 patients diagnosed with breast cancer from January 1992 to December 2016 within the 13 Surveillance, Epidemiology, and End Results (SEER) registries (SEER cohort). Eligible patients were aged 20 to 84 years, diagnosed with stage I to III disease, and who had breast cancer surgery and survived for ≥ 1 year after diagnosis. The outcome of interest was any thoracic soft-tissue sarcoma (angiosarcomas and other subtypes) that developed ≥ 1 year after breast cancer diagnosis.
Radiotherapy was the strongest risk factor for thoracic soft-tissue sarcoma in both cohorts. This finding, along with the novel findings for diabetes and hypertension as potential risk factors for angiosarcomas, warrant further investigation as potential targets for prevention strategies and increased surveillance.— Veiga et al
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Key Findings
In the KP cohort, median follow-up was 9.3 years (interquartile range [IQR] = 5.7–13.9 years). Thoracic soft-tissue sarcomas developed in 19 (0.1%) of 15,940 survivors, including 11 angiosarcomas and 8 of other subtypes. Overall, 18 (94.7%) of 19 sarcomas occurred in women treated with radiotherapy (relative risk [RR] = 8.1, 95% confidence interval [CI] = 1.1–60.4, P = .0052); no associations with prescribed dose, fractionation, or boost were observed. Elevated risk for angiosarcoma was observed with receipt of anthracyclines (RR = 3.6, 95% CI = 1.0–13.3, P = .058) and elevated risk of other sarcoma subtypes was associated with receipt of alkylating agents (RR = 7.7, 95% CI = 1.2–150.8, P = .026). Elevated risk of angiosarcoma was observed for patients with a history of hypertension (RR = 4.8, 95% CI = 1.3–17.6, P = .017) and a history of diabetes (RR = 5.3, 95% CI = 1.4–20.8, P = .036).
In the SEER cohort, median follow-up was 8.3 years (IQR = 4.3–13.9 years). Sarcomas developed in 430 (0.1%) of 457,300 survivors, including 268 angiosarcomas and 162 of other subtypes. Overall, 335 (77.9%) of 430 cases occurred after radiotherapy (RR = 3.0, 95% CI = 2.4–3.8, P < .0001). For angiosarcomas, the relative risk associated with breast-conserving surgery plus radiotherapy vs mastectomy plus radiotherapy was 1.9 (95% CI = 1.1–3.3, P = .012).
At 10 years after radiotherapy, the cumulative incidence of thoracic soft-tissue sarcoma was 0.21% (95% CI = 0.12%–0.34%) in the KP cohort and 0.15% (95% CI = 0.13%–0.17%) in the SEER cohort.
The investigators concluded, “Radiotherapy was the strongest risk factor for thoracic soft-tissue sarcoma in both cohorts. This finding, along with the novel findings for diabetes and hypertension as potential risk factors for angiosarcomas, warrant further investigation as potential targets for prevention strategies and increased surveillance.”
Lene H.S. Veiga, PhD, of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the National Cancer Institute and National Institutes of Health. For full disclosures of the study authors, visit thelancet.com.
