Proton therapy in young breast cancer patients with germline TP53 and ATM mutations: a case series

Young breast cancer patients with germline radiosensitivity mutations, such as in TP53 and ATM, face an increased risk of radiation-induced toxicities and secondary malignancies. Proton therapy offers dosimetric advantages by reducing the radiation exposure of healthy tissues, potentially mitigating these risks. However, clinical data on the use of proton therapy in this specific population are limited.

We conducted a single-center retrospective study in patients with non-metastatic breast cancer with germline TP53 or ATM mutations treated with intensity-modulated proton therapy (IMPT) at the Institut Curie Proton Therapy Center between June 2019 and November 2024. Patient demographics, treatment characteristics, and toxicity profiles were analyzed. Acute and late toxicities were graded according to CTCAE v5.0. Survival outcomes were calculated from the date of histological diagnosis.

Four young patients (median age 25 years; range 24-29) with TP53 (n = 2) or ATM (n = 2) mutations received IMPT targeting the chest wall and regional lymph nodes. All patients had hormone receptor-positive, node-positive breast cancer; one patient was also HER2 positive. Treatments included chemotherapy, surgery, and adjuvant hormonal therapy; three patients received additional targeted therapies. The median mean heart dose was 1.25 Gy (range 0.5-1.5 Gy). One patient experienced acute grade 2 radiodermatitis, while two patients had grade 1 radiodermatitis. After a median follow-up of 18 months (range 11-49 months), one patient exhibited persistent grade 1 skin pigmentation. No other late toxicities, including cardiac or pulmonary complications, were observed. There were no secondary malignancies or recurrences, resulting in 100% overall and recurrence-free survival.

Proton therapy was well tolerated in this small cohort of young breast cancer patients with germline TP53 or ATM mutations, demonstrating minimal acute toxicity and no significant late effects over a median follow-up of 18 months. These preliminary findings suggest that proton therapy may be a safe treatment option for this high-risk population. Larger studies with extended follow-up are necessary to confirm these results and to inform clinical guidelines.