Results from a retrospective cohort study indicated that radiotherapy for breast cancer appears to be a significant risk factor for developing chest soft tissue sarcoma.

Radiation therapy appears to be significantly associated with the risk of thoracic soft tissue sarcoma in breast cancer patients, while diabetes and hypertension were strong potential predictors of angiosarcoma, according to data from a retrospective study recently published in Lancet oncology.

The investigators examined two data sets, including data from the Kaiser Permanente (KP) cohort, which associated radiotherapy with an eight-fold higher relative risk (RR) for thoracic soft tissue sarcoma (RR 8.1; 95% CI 1.1-60.4; s = 0. s <.0001). In addition, further analysis of the KP cohort showed that the RR for developing angiosarcoma was 3.6 (95% CI 1.0–13.3; s = .058) after treatment with anthracyclines and RR 7.7 for the development of other sarcomas after treatment with alkylating agents (RR 7.7; 95% CI 1.2-150.8; s = .026). Furthermore, the RR for developing angiosarcoma among those with a history of hypertension (95% CI, 1.3-17.6; s = .017) and diabetes (95% CI, 1.4–20.8; s = .036) was 4.8 and 5.3, respectively.

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

The study evaluated 15,940 patients with unilateral invasive primary breast cancer who survived for at least 1 year after diagnosis in the KP group, as well as 457,300 patients in the SEER group who were diagnosed with breast cancer. Median follow-up was 9.3 years (IQR 5.7-13.9) in the KP group and 8.3 years (IQR 4.3-13.9) in the SEER group. The two groups of survivors had similar demographic characteristics, with the mean ages at breast cancer diagnosis being 61 years (IQR 52-70) in the overall group (n=15940).

Soft tissue tumors occurred in approximately 0.1% of patients in the total group, amounting to 19 patients in the KP group and 430 in the SEER group. Most cases in both groups were hemangiosarcoma (n = 268), most of which occurred after radiotherapy (77.9%). As a result, radiotherapy was associated with an increased risk of thoracic soft tissue sarcoma (RR, 3.0; 95% CI, 2.4-3.8; s <.00001). Furthermore, for hemangiosarcoma, breast-conserving surgery and radiotherapy compared to mastectomy and radiotherapy resulted in a relative risk rate of 1.9 (95% CI, 1.1–3.3; s = .012).

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


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

Leave a Reply