So you’re saying there’s a chance.

Top Line: What is the risk of thoracic soft tissue sarcoma after breast radiation?

The Study: This population-based study used two large cohorts from Kaiser Permanente (n=15,940) and SEER (n=457,900) to evaluate factors associated with the development of thoracic STS after treatment. In the KP cohort, 19 patients (0.1%) developed thoracic STS with a median latency period of 5.5 years. Almost all (18 of 19, 94.7%) received radiation. Of the 16 STS cases that could be localized from pathology reports, 15 (93.8%) were ipsilateral to the primary breast cancer. Among breast cancer treatments, radiation (RR 8.1), alkylating agents (RR 7.7), and anthracyclines (RR 3.6) increased the risk of developing STS. Most of the sarcomas were angiosarcoma (11 of 19, 57.9%). Radiation treatment factors such as dose, fractionation, energy, etc. were not associated with STS risk. The SEER cohort had very similar findings with 0.1% of patients developing thoracic STS at a median of 7.1 years after treatment. Again, most cases of STS (86.5%) had prior radiation. Interestingly, hypertension and diabetes were also associated with increased risk of angiosarcoma. In addition, most angiosarcomas occurred after breast conservation surgery and RT rather than mastectomy and RT. A resulting hypothesis is that angiosarcoma may develop through a pathway of breast lymphedema following BCS and RT in patients with baseline risk factors. So, how does thoracic STS risk compare with other rare outcomes from breast cancer treatment? The rate of 30-day mortality after curative surgery for breast cancer surgery is 0.26%. In a meta-analysis of adjuvant tamoxifen trials, there was a 2.6% absolute increase in the 15-year incidence of uterine cancer among women ≥55. The estimated cumulative risk of developing a bone marrow neoplasm (myelodysplastic syndrome or AML) after adjuvant doxorubicin and cyclophosphamide is 0.5% at 10 years. In other words, this study helps provide a better way to assess the risk of rare adverse outcomes among breast cancer survivors.

TBL: While the absolute risk is low, the risk of thoracic STS appears to be higher among breast cancer survivors treated with radiation among a number of other treatment and patient-specific factors. | Veiga, Lancet Oncol 2022