Radiotherapy Increases Sarcoma Risk in TP53 Breast Cancer

TOPLINE: 
Patients with breast cancer carrying TP53 pathogenic variants face an 8.8% cumulative risk for developing sarcoma within 15 years of receiving radiotherapy. However, the 10-year cumulative risk of developing any secondary cancer was high in patients with TP53 pathogenic variants, regardless of whether they received radiotherapy.
METHODOLOGY:
The risk for secondary cancers in patients with breast cancer carrying the TP53 germline variants is not well understood.
To evaluate the risk for sarcoma following radiotherapy, researchers evaluated 91 patients with breast cancer harboring TP53 germline variants who had previously undergone surgery. TP53 variants were classified as likely pathogenic or variants of unknown significance.
Of the 91 patients, 40 received radiotherapy (28 were likely pathogenic; 12 had variants of unknown significance) and 51 did not receive radiotherapy (41 were likely pathogenic; 10 had variants of unknown significance).
The median follow-up was 14 years for likely pathogenic TP53 carriers (median age, 35 years) who received radiotherapy and 11 years for the propensity score-matched control cohort of 420 patients without TP53 pathogenic variants (median age, 38 years).
Patients who received radiotherapy had more advanced tumors, greater axillary node involvement, and higher-grade tumors. The primary outcome was the cumulative incidence of in-field sarcoma, with the in-field region including ipsilateral thoracic organs as well as ipsilateral neck and thyroid.
TAKEAWAY:
Among the 28 pathogenic TP53 pathogenic variant carriers who received radiotherapy, 3 developed a secondary in-field sarcoma for a cumulative incidence of 8.8% at 15 years. No events occurred in the matched controls or other two groups (carriers of the TP53 variant of unknown significance who received radiotherapy; carriers of either TP53 variant who did not receive radiotherapy).
The cumulative incidence of developing any secondary cancer over a 10-year period was 22.5% in TP53 pathogenic variant carriers who received radiotherapy and 38% in those who did not receive radiotherapy, but the difference was not statistically significant (P = .55).
Overall survival was also not significantly different between TP53 pathogenic variant carriers who received radiotherapy and those who did not.
No deaths due to radiotherapy-associated sarcoma were reported.
IN PRACTICE:
“Our results highlight that TP53 pathogenic variant carriers face substantial overall risk of any secondary cancers, most of which develop unrelated to [radiotherapy],” the authors wrote, emphasizing that “iatrogenic risk of radiotherapy must be balanced against its anticipated therapeutic benefit particularly among patients with higher risk breast cancer.”
SOURCE:
The study, led by Gustav Y. Cederquist, MD, PhD, resident physician within the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center, New York City, was published online in JAMA Oncology.
LIMITATIONS:
The study limitations include a modest sample size. The retrospective and deidentified nature of the analyses may introduce biases. Additionally, the study could not capture all long-term outcomes.
DISCLOSURES:
The authors did not disclose any funding information or conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
 
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