There are several factors that may increase the risk of thoracic soft tissue sarcoma in patients with a history of breast cancer, according to a study published in The Lancet Oncology.

Researchers found that radiotherapy and breast-conserving surgery were associated with an increased risk of thoracic soft tissue sarcomas.

The study also showed, for the first time, that diabetes and hypertension are potential risk factors for angiosarcoma in patients with a history of breast cancer.

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“These factors might be potential targets for future prevention strategies and identification of patients who should receive increased surveillance,” the study authors wrote.

The authors conducted this study using data from 2 large cohorts of women with stage I-III breast cancer. The patients were 20-84 years of age at diagnosis, had undergone breast cancer surgery, and had survived at least 1 year after breast cancer diagnosis.

One cohort included 15,940 patients from the Kaiser Permanente (KP) database who were diagnosed with breast cancer between January 1, 1990, and December 31, 2016. The other cohort included 457,300 patients from the Surveillance, Epidemiology, and End Results (SEER) registry who were diagnosed between January 1, 1992, and December 31, 2016.

The median follow-up was 9.3 years in the KP cohort and 8.3 years in the SEER cohort. In both cohorts, 0.1% of patients developed thoracic soft tissue sarcomas, with angiosarcoma being the most common subtype.

Receipt of radiotherapy was significantly associated with the development of thoracic soft tissue sarcoma in both cohorts. The relative risk (RR) was 8.1 (95% CI, 1.1-60.4; P =.0052) in the KP cohort and 3.0 (95% CI, 2.4-3.8; P <.0001) in the SEER cohort. Radiotherapy dose, fractionation, and boost were not associated with the risk of thoracic soft tissue sarcoma.

In the KP cohort, there was an increased risk of thoracic soft tissue sarcoma among patients with hypertension (RR, 4.8; 95% CI, 1.3-17.6; P =.017) or diabetes (RR, 5.3; 95% CI, 1.4-20.8; P =.036) at breast cancer diagnosis. The risk increased if both comorbidities were present (RR, 8.4; 95% CI, 1.5-47.3; P =.038). This evaluation was not reported for the SEER cohort.

“The striking effect for hypertension and diabetes at the time of breast cancer diagnosis is a novel finding, and the potential role of these comorbidities in the cause and prevention of this life-threatening disease warrants further investigation,” the authors wrote.

In the SEER cohort, patients who had breast-conserving surgery had an increased risk of any thoracic soft tissue sarcoma (RR, 2.3; 95% CI, 1.7-3.1; P <.0001) and angiosarcoma (RR, 3.7; 95% CI, 2.3-6.0; P <.0001), compared with patients who underwent mastectomy. 

In the KP cohort, treatment with anthracyclines was associated with an increased risk of angiosarcoma, though not significantly (RR, 3.6; 95% CI, 1.0-13.3; P =.058). Alkylating agents were associated with an increased risk of other soft tissue sarcomas (RR, 7.7; 95% CI, 1.2-150.8; P =.026). Specific types of chemotherapy could not be evaluated in the SEER cohort. 


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