In a study published as a research letter in JAMA Oncology, Cederquist et al found that patients with breast cancer who received adjuvant radiation therapy and harbored likely pathogenic TP53 germline variants were at increased risk of developing secondary in-field sarcoma during follow-up.
Study Details
The study involved data on patients from prospectively maintained institutional databases (OncoKB, ClinVar) who underwent primary surgical management of breast cancer and had TP53 germline variants. The primary outcome measure was cumulative incidence of in-field sarcoma among patients harboring TP53 pathogenic variants.
The at-risk in-field region included ipsilateral thoracic organs; the ipsilateral neck and thyroid were included if patients received supraclavicular node radiation therapy. A propensity score–matched control cohort was derived from a database of patients without TP53 germline variants who received adjuvant radiation therapy.
Key Findings
A total of 91 patients with TP53 germline variants were identified; of these patients, 40 received radiation therapy (28 with pathogenic variants, 12 with variants of unknown significance). A total of 51 patients did not receive radiation therapy (41 with pathogenic variants, 10 with variants of unknown significance).
Median follow-up was 14 years (interquartile range [IQR] = 8–18 years) among carriers of TP53 pathogenic variants who received radiation therapy and 11 years (IQR = 8–12 years) in the propensity score–matched control group. Among 28 carriers of TP53 pathogenic variants who received radiation therapy, 3 developed a secondary in-field sarcoma (15-year risk = 8.8%, 95% confidence interval [CI] = 1.4%–25%) compared with no in-field sarcoma among 420 propensity score–matched controls (P < .001). No in-field sarcomas were observed among 12 carriers of TP53 variants of unknown significance who received radiation therapy or among the 51 carriers of TP53 variants who had not received radiation therapy.
The 10-year cumulative incidence of any secondary cancer was 22.5% (95% CI = 8.8%–40.0%) among carriers of TP53 pathogenic variants who received radiation therapy and 38% (95% CI = 15%–61%) among those who did not receive radiation therapy (P = .55). No deaths were attributable to radiation therapy–associated sarcomas.
The investigators concluded: “To our knowledge, this is the largest analysis of radiation therapy–associated cancer risk among patients with breast cancer harboring TP53 germline variants. We estimate the longitudinal risk of radiation therapy–associated sarcoma among carriers of TP53 pathogenic variants to be 8.8% at 15 years—significantly increased compared with that of the general population.”
Lior Z. Braunstein, MD, of the Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, is the corresponding author of the JAMA Oncology article.
Disclosure: The study authors reported no conflicts of interest.
