Radiotherapy in patients with breast cancer and Li-Fraumeni syndrome — a narrative review
Abstract
Li-Fraumeni syndrome (LFS) is a rare disorder that increases the risk of many cancers, including breast cancer (BC), leukemia, soft-tissue sarcomas, central nervous system tumors, and adrenocortical carcinomas. Several previous clinical observations have shown that families with LFS are at higher risk of secondary radiotherapy-induced malignancies. This review article summarizes the available information about secondary malignancies in LFS patients who were treated with radiation therapy. A total of two electronic databases (PubMed and Web of Science) were searched using key words that included ‘Li- Fraumeni Syndrome’, ‘breast cancer’, and ‘radiotherapy’ from their inception to February 2022. Studies reporting radiosensitivity, cancer, and radiotherapy-induced secondary neoplasms were summarized. The majority of the data that were found concerned radiotherapy in patients with BC with LFS, including radiotherapy-induced malignancy. According to recommendations, radiotherapy should be used with caution and adapted to minimize the risk of secondary malignant neoplasms. The potential risk of loco-regional recurrence without radiotherapy or the long-term risk of radiation-induced malignancies must be taken into account when considering adjuvant radiotherapy for LFS and BC patients.
Keywords: breast cancerLi-Fraumeni syndromeradiotherapyradiation-induced malignancies
References
- Li FP, Fraumeni JF, Mulvihill JJ, et al. A cancer family syndrome in twenty-four kindreds. Cance Res. 1988; 48: 5358–5362.
- Viskochil D, Buchberg AM, Xu G, et al. Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus. Cell. 1990; 62(1): 187–192.
- Kumamoto T, Yamazaki F, Nakano Y, et al. Medical guidelines for Li-Fraumeni syndrome 2019, version 1.1. Int J Clin Oncol. 2021; 26(12): 2161–2178.
- Aubrey BJ, Strasser A, Kelly GL. Tumor-Suppressor Functions of the TP53 Pathway. Cold Spring Harb Perspect Med. 2016; 6(5).
- Monti P, Menichini P, Speciale A, et al. Heterogeneity of Mutations and P53 Protein Residual Function in Cancer: Does It Matter? Front Oncol. 2020; 10: 593383.
- Lee JM, Abrahamson JL, Kandel R, et al. Susceptibility to radiation-carcinogenesis and accumulation of chromosomal breakage in p53 deficient mice. Oncogene. 1994; 9(12): 3731–3736.
- Schneider K, Zelley K, Nichols KE, et al. Li–Fraumeni syndrome. In: Pagon RA, Adam MP, Bird TD, et al. ed. GeneReviews. University of Washington, Seattle 1993.
- Chompret A, Brugières L, Ronsin M, et al. P53 germline mutations in childhood cancers and cancer risk for carrier individuals. Br J Cancer. 2000; 82(12): 1932–1937.
- McCuaig JM, Armel SR, Novokmet A, et al. Routine TP53 testing for breast cancer under age 30: ready for prime time? Fam Cancer. 2012; 11(4): 607–613.
- Tinat J, Bougeard G, Baert-Desurmont S, et al. 2009 version of the Chompret criteria for Li Fraumeni syndrome. J Clin Oncol. 2009; 27(26): e108–9; author reply e110.
- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Genetic/Familial High-Risk Assessment: Breast and Ovarian. NCCN Guidelines Version 1.2023 Li-Fraumeni Syndrome Management.
- Guha T, Malkin D. Inherited Mutations and the Li-Fraumeni Syndrome. Cold Spring Harb Perspect Med. 2017; 7(4).
- Mai PL, Best AF, Peters JA, et al. Risks of first and subsequent cancers among TP53 mutation carriers in the National Cancer Institute Li-Fraumeni syndrome cohort. Cancer. 2016; 122(23): 3673–3681.
- Page M, McKenzie J, Bossuyt P, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021: n71.
- Schon K, Tischkowitz M. Clinical implications of germline mutations in breast cancer: TP53. Breast Cancer Res Treat. 2018; 167(2): 417–423.
- Cirauqui B, Morán T, Estival A, et al. Breast Cancer Patient with Li-Fraumeni Syndrome: A Case Report Highlighting the Importance of Multidisciplinary Management. Case Rep Oncol. 2020; 13(1): 130–138.
- Hisada M, Garber JE, Fung CY, et al. Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst. 1998; 90(8): 606–611.
- Masciari S, Dillon DA, Rath M, et al. Breast cancer phenotype in women with TP53 germline mutations: a Li-Fraumeni syndrome consortium effort. Breast Cancer Res Treat. 2012; 133(3): 1125–1130.
- Melhem-Bertrandt A, Bojadzieva J, Ready KJ, et al. Early onset HER2-positive breast cancer is associated with germline TP53 mutations. Cancer. 2012; 118(4): 908–913.
- Li X, Chen X, Wen L, et al. Impact of TP53 mutations in breast cancer: Clinicopathological features and prognosisImpact of TP53 mutations in breast CA. Thorac Cancer. 2020; 11(7): 1861–1868.
- Zhou F, Zhang Y, Xu X, et al. Establishment and characterization of three stable Basal/HER2-positive breast cancer cell lines derived from Chinese breast carcinoma with identical missense mutations in the DNA-binding domain of TP53. Cancer Cell Int. 2018; 18: 118.
- Liu H, Murphy CJ, Karreth FA, et al. Identifying and Targeting Sporadic Oncogenic Genetic Aberrations in Mouse Models of Triple-Negative Breast Cancer. Cancer Discov. 2018; 8(3): 354–369.
- Lindahl T, Landberg G, Ahlgren J, et al. Overexpression of cyclin E protein is associated with specific mutation types in the p53 gene and poor survival in human breast cancer. Carcinogenesis. 2004; 25(3): 375–380.
- Feeley LP, Mulligan AM, Pinnaduwage D, et al. Distinguishing luminal breast cancer subtypes by Ki67, progesterone receptor or TP53 status provides prognostic information. Mod Pathol. 2014; 27(4): 554–561.
- Wilson JRF, Bateman AC, Hanson H, et al. A novel HER2-positive breast cancer phenotype arising from germline TP53 mutations. J Med Genet. 2010; 47(11): 771–774.
- Morton LM, Onel K, Curtis RE, et al. The rising incidence of second cancers: patterns of occurrence and identification of risk factors for children and adults. Am Soc Clin Oncol Educ Book. 2014: e57–e67.
- Mullenders L, Atkinson M, Paretzke H, et al. Assessing cancer risks of low-dose radiation. Nat Rev Cancer. 2009; 9(8): 596–604.
- Dracham CB, Shankar A, Madan R. Radiation induced secondary malignancies: a review article. Radiat Oncol J. 2018; 36(2): 85–94.
- Boyle JM, Spreadborough A, Greaves MJ, et al. The relationship between radiation-induced G(1)arrest and chromosome aberrations in Li-Fraumeni fibroblasts with or without germline TP53 mutations. Br J Cancer. 2001; 85(2): 293–296.
- Bougeard G, Renaux-Petel M, Flaman JM, et al. Revisiting Li-Fraumeni Syndrome From TP53 Mutation Carriers. J Clin Oncol. 2015; 33(21): 2345–2352.
- Limacher JM, Frebourg T, Natarajan-Ame S, et al. Two metachronous tumors in the radiotherapy fields of a patient with Li-Fraumeni syndrome. Int J Cancer. 2001; 96(4): 238–242.
- 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(2): 187–192.
- Le AN, Harton J, Desai H, et al. Frequency of radiation-induced malignancies post-adjuvant radiotherapy for breast cancer in patients with Li-Fraumeni syndrome. Breast Cancer Res Treat. 2020; 181(1): 181–188.
- Salmon A, Amikam D, Sodha N, et al. Rapid development of post-radiotherapy sarcoma and breast cancer in a patient with a novel germline 'de-novo' TP53 mutation. Clin Oncol (R Coll Radiol). 2007; 19(7): 490–493.
- Hisada M, Garber JE, Fung CY, et al. Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst. 1998; 90(8): 606–611.
- 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.
- Barbosa OV, Reiriz AB, Boff RA, et al. Angiosarcoma in previously irradiated breast in patient with Li-Fraumeni syndrome. A case report. Sao Paulo Med J. 2015; 133(2): 151–153.
- Nandikolla AG, Venugopal S, Anampa J. Breast cancer in patients with Li-Fraumeni syndrome - a case-series study and review of literature. Breast Cancer (Dove Med Press). 2017; 9: 207–215.
- Henry E, Villalobos V, Million L, et al. Chest wall leiomyosarcoma after breast-conservative therapy for early-stage breast cancer in a young woman with Li-Fraumeni syndrome. J Natl Compr Canc Netw. 2012; 10(8): 939–942.
- Petry V, Bonadio RC, Cagnacci AQ, et al. Radiotherapy-induced malignancies in breast cancer patients with TP53 pathogenic germline variants (Li-Fraumeni syndrome). Fam Cancer. 2020; 19(1): 47–53.
- Kast K, Krause M, Schuler M, et al. Late onset Li-Fraumeni Syndrome with bilateral breast cancer and other malignancies: case report and review of the literature. BMC Cancer. 2012; 12: 217.
- Wong P, Han K. Lack of toxicity in a patient with germline TP53 mutation treated with radiotherapy. Curr Oncol. 2014; 21(2): e349–e353.
- Hendrickson PG, Luo Y, Kohlmann W, et al. Radiation therapy and secondary malignancy in Li-Fraumeni syndrome: A hereditary cancer registry study. Cancer Med. 2020; 9(21): 7954–7963.
- Frebourg T, Bajalica Lagercrantz S, Oliveira C, et al. European Reference Network GENTURIS. Guidelines for the Li-Fraumeni and heritable TP53-related cancer syndromes. Eur J Hum Genet. 2020; 28(10): 1379–1386.
- Chung CS, Yock TI, Nelson K, et al. Incidence of second malignancies among patients treated with proton versus photon radiation. Int J Radiat Oncol Biol Phys. 2013; 87(1): 46–52.
- Paganetti H, Moteabbed M, Athar B, et al. SU-E-T-258: Assessment of Radiation Induced Second Cancer Risks in Proton Therapy and IMRT for Organs inside the Main Radiation Field. Med Phys. 2012; 39(6Part13): 3762–3763.
- Niemantsverdriet M, van Goethem MJ, Bron R, et al. High and low LET radiation differentially induce normal tissue damage signals. Int J Radiat Oncol Biol Phys. 2012; 83(4): 1291–1297.
- Eley JG, Friedrich T, Homann KL, et al. Comparative Risk Predictions of Second Cancers After Carbon-Ion Therapy Versus Proton Therapy. Int J Radiat Oncol Biol Phys. 2016; 95(1): 279–286.
- Thariat J, Chevalier F, Orbach D, et al. Avoidance or adaptation of radiotherapy in patients with cancer with Li-Fraumeni and heritable TP53-related cancer syndromes. Lancet Oncol. 2021; 22(12): e562–e574.
- Iwasaki T, Mizumoto M, Numajiri H, et al. Re-irradiation using proton therapy for radiation-induced secondary cancer with Li-Fraumeni syndrome: A case report and review of literature. J Cancer Res Ther. 2020; 16(6): 1524–1527.
- Paluch-Shimon S, Cardoso F, Partridge AH, et al. ESO-ESMO 4th International Consensus Guidelines for Breast Cancer in Young Women (BCY4). Ann Oncol. 2020; 31(6): 674–696.
- Tung NM, Boughey JC, Pierce LJ, et al. Management of Hereditary Breast Cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline. J Clin Oncol. 2020; 38(18): 2080–2106.
- Trombetta MG, Dragun A, Mayr NA, et al. ASTRO Radiation Therapy Summary of the ASCO-ASTRO-SSO Guideline on Management of Hereditary Breast Cancer. Pract Radiat Oncol. 2020; 10(4): 235–242.