328P - Frequency of radiotherapy-induced malignancies in Li-Fraumeni syndrome patients with early breast cancer and influence of the radiotherapy technique

Background

Breast cancer (BC) is the most common malignancy in female patients (pts) with Li-Fraumeni Syndrome (LFS). These pts are at increased risk of other malignancies, including radiotherapy-induced malignancies (RIM) that are those occurring in a previously irradiated field. We aimed to evaluate the frequency of RIM and other oncologic outcomes of LFS pts with eBC.

Methods

We evaluated pts with a germline pathogenic/likely pathogenic variant of TP53 (LFS) diagnosed with eBC and followed by the Hereditary Cancer Team of a single cancer center between Dec/99 and Apr/23. The primary endpoint was the frequency of RIM among pts treated with adjuvant RT.

Results

Forty-nine pts were evaluated. Median age was 39 years (range 21 - 62); 79% were ER-positive; 35% HER2-positive; 35% stage I and 27% stage II; and 71% had TP53 R337H variant. Most pts (87%) were unaware of the LFS at the time of BC treatment. Regarding treatment, 62% underwent a mastectomy, 66% (neo)adjuvant chemotherapy, and 62% RT. The use of RT was more common after conservative surgery as expected (87% vs 46% with mastectomy, P=0.010). Oncologic outcomes are summarized in the table. Among 30 pts treated with RT, 4 (13.8%) developed RIM in the irradiated field (3 soft tissue malignancies and 1 BC). The occurrence of RIM was not influenced by RT dose (≤ 40.8 or > 40.8), but was influenced by the type of RT. RIM was observed in 100% with 2D RT (n=2/2), 100% (n=1/1) with volumetric modulated arc therapy (VMAT), 6% (n=1/16) with 3D RT, and 0% with intensity-modulated RT (n=0/1) (P=0.007). Table: 328P

Conclusions

Our study confirms an alarming rate of RIM after adjuvant RT, highlighting the need for a careful risk-benefit evaluation for the indication of RT, which should be preferentially avoided if possible. Despite the small numbers in each subgroup, the risk of RIM seemed to be influenced by the RT technique, with higher rates with 2D RT and VMAT. Early TP53 testing is crucial to guide the BC treatment plan.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

V. Petry: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Novartis. R. Colombo Bonadio: Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Gilead, Nestle Health, Zodiac; Financial Interests, Personal, Expert Testimony: Ache; Financial Interests, Institutional, Research Funding: Novartis, AstraZeneca. L. Testa: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Novartis, Daiichi Sankyo, MSD; Financial Interests, Institutional, Research Funding: Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Daiichi Sankyo, MSD, Lilly, Zodiac, Pfizer. All other authors have declared no conflicts of interest.