- TP53 is a tumor suppressor gene:
- That plays a crucial role in:
- Maintaining genomic stability and regulating cell cycle checkpoints
- That plays a crucial role in:
- Carriers of a TP53 pathogenic variant:
- Would be expected to be unable to repair tissue damage from DNA-damaging radiotherapy and be at risk for significant radiotherapy-associated sequelae
- Outcomes reported in published case reports:
- Support this recommendation against radiotherapy in women with breast cancer who are carriers of a TP53 pathogenic variants:
- Due to increased risk of radiation-induced secondary malignancies
- Support this recommendation against radiotherapy in women with breast cancer who are carriers of a TP53 pathogenic variants:
- Mutations in TP53 are considered:
- An absolute contraindication of radiotherapy:
- Except in those with a significantly high risk of locoregional recurrence
- Mastectomy is the recommended therapeutic surgical option
- An absolute contraindication of radiotherapy:
- The radiotherapy-induced toxicity spectrum in patients with breast cancer carrying ATM pathogenic variants is controversial:
- Seven studies identified in a systematic review addressed radiotherapy after breast-conserving surgery among women with breast cancer who harbor ATM pathogenic variants:
- Meyer et al found no significant differences in local relapse-free survival in a cohort of 138 patients with early stage breast cancer treated with breast-conserving surgery, followed by radiotherapy, of whom 20 were found to carry either an ATM truncating or missense variant:
- They concluded that the results do not support the hypothesis that patients with breast cancer carrying a sequence variant in the ATM gene differentially benefit from postoperative radiotherapy
- Meyer et al found no significant differences in local relapse-free survival in a cohort of 138 patients with early stage breast cancer treated with breast-conserving surgery, followed by radiotherapy, of whom 20 were found to carry either an ATM truncating or missense variant:
- Seven studies identified in a systematic review addressed radiotherapy after breast-conserving surgery among women with breast cancer who harbor ATM pathogenic variants:
- According to the ASCO-ASTRO-SSO Consensus recommendations for carriers of BRCA 1/2 and other germline pathogenic variants,:
- Women with breast cancer may safely be offered radiotherapy when clinically indicated
- Data on toxicity rates comparing carriers of ATM pathogenic variants and noncarriers:
- Do not favor avoiding radiotherapy:
- Potential absolute risks do not appear to be significant:
- However, more research is needed
- Potential absolute risks do not appear to be significant:
- Do not favor avoiding radiotherapy:
- A discussion with ATM carriers interested in breast-conserving therapy is encouraged
- There is no evidence of increased toxicity or contralateral breast cancer events from radiation exposure in BRCA 1/2, CHEK2, CDH1 carriers
- References:
- Trombetta MG, Dragun A, Mayr NA, Pierce LJ. ASTRO Radiation Therapy Summary of the ASCO-ASTRO-SSO Guideline on Management of Hereditary Breast Cancer. Pract Radiat Oncol. 2020;10:235-242.
- Lazzari G, Buono G, Zannino B, Silvano G. Breast cancer adjuvant radiotherapy in BRCA1/2, TP53, ATM genes mutations: Are there solved issues? Breast Cancer (Dove Med Press). 2021;13:299-310.
- Ferrarini A, Auteri-Kaczmarek A, Pica A, et al. Early occurrence of lung adenocarcinoma and breast cancer after radiotherapy of a chest wall sarcoma in a patient with a de novo germline mutation in TP53. Fam Cancer. 2011;10:187-192.
- Heymann S, Delaloge S, Rahal A, et al. Radio-induced malignancies after breast cancer postoperative radiotherapy in patients with Li- Fraumeni syndrome. Radiat Oncol. 2010;5:104.
- Meyer A, John E, Dörk T, Sohn C, Karstens JH, Bremer M. Breast cancer in female carriers of ATM gene alterations: outcome of adjuvant radiotherapy. Radiother Oncol. 2004;72: 319-323.
Rodrigo Arrangoiz MS, MD, FACS, FSSO 