Data Show Elevated Risk of Thoracic Soft Tissue Sarcomas After Radiotherapy Treatment for Breast Cancer

Findings from a retrospective cohort study indicated that radiotherapy treatment for breast cancer appeared to be a significant risk factor in developing thoracic soft tissue sarcoma.

Radiotherapy appears to be associated significantly increased risk of developing thoracic soft tissue sarcomas in patients with breast cancer, while diabetes and hypertension were strong potential predictors for angiosarcomas, according to data from a retrospective cohort study published recently in the Lancet Oncology.

Investigators examined 2 datasets, including data from the Kaiser Permanente (KP) cohort—which linked radiotherapy with an 8-fold higher relative risk (RR) of thoracic soft tissue sarcoma (RR 8.1; 95% CI 1.1-60.4; P = .0052)—and the larger Surveillance, Epidemiology, and End Results (SEER) 13 registries cohort produced similar results, associating radiotherapy with a threefold higher risk of soft tissue sarcoma (RR 3.0; 95% CI, 2.4-3.8; P <.0001). Additionally, further analysis of the KP cohort showed a RR of developing angiosarcoma of 3.6 (95% CI 1.0-13.3; P = .058) after treatment with anthracyclines and a RR of 7.7 of developing other sarcomas after treatment with alkylating agents (RR 7.7; 95% CI 1.2-150.8; P = .026). Moreover, the RR of developing angiosarcoma among those with a history of hypertension (95% CI, 1.3-17.6; P =.017) and diabetes (95% CI, 1.4-20.8; P =.036) was 4.8 and 5.3, respectively.

“To our knowledge, this is the first study to assess history of cardiovascular risk factors in subsequent soft tissue sarcoma risk. We found a striking effect for hypertension and diabetes before breast cancer diagnosis as possible novel risk factors for thoracic angiosarcoma,” the investigators wrote. “Hypertension and diabetes are also probably risk factors for lymphoedema after breast cancer treatment.”

The study assessed 15,940 patients with unilateral first primary invasive breast cancer who survived at least 1 year after diagnosis in the KP cohort, as well as 457,300 patients with the in the SEER cohort who were diagnosed with breast cancer. Median follow-up was 9.3 years (IQR 5.7-13.9) in the KP cohort and 8.3 years (IQR 4.3-13.9) in the SEER cohort. The two groups of survivors had similar demographic characteristics, with median ages at breast cancer diagnosis of 61 years (IQR 52-70) in the overall cohort (n = 15,940).

Soft tissue sarcomas occurred in roughly 0.1% of patients in the overall cohort, amounting to 19 patients in the KP cohort and 430 in the SEER cohort. Most of the cases in both cohorts were angiosarcomas (n = 268), the majority of which occurred after radiotherapy (77.9%). Due to this, radiotherapy was associated with a notably increased risk of developing thoracic soft tissue sarcoma (RR, 3.0; 95% CI, 2.4-3.8; P <.00001). Moreover, for angiosarcomas, breast conserving surgery and radiotherapy compared with mastectomy and radiotherapy resulted in a RR of 1.9 (95% CI, 1.1-3.3; P =.012).

“The potential role of these comorbidities warrants further investigation, to reveal possible targets for future prevention strategies and increased surveillance,” investigators concluded.


Veiga LHS, Vo JB, Curtis RE, et al. Treatment-related thoracic soft tissue sarcomas in US breast cancer survivors: a retrospective cohort study. Lancet Oncol. Published online October 11, 2022. doi:10.1016/S1470-2045(22)00561-7