Radio-induced malignancies after breast cancer postoperative radiotherapy in patients with Li-Fraumeni syndrome

Steve Heymann,Suzette Delaloge,Marie-Christine Mathieu,Thierry Frebourg,Corinne Pachet,Céline Bourgier,Olivier Caron,Hugo Marsiglia,Arslane Rahal,Lise Barreau

doi:10.1186/1748-717x-5-104

Steve Heymann, Suzette Delaloge + Show 8 more

Open Access

https://doi.org/10.1186/1748-717x-5-104

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Abstract

BackgroundThere are no specific recommendations for the management of breast cancer patients with germ-line p53 mutations, an exceptional genetic condition, particularly regarding postoperative radiotherapy. Preclinical data suggested that p53 mutations conferred enhanced radiosensitivity in vitro and in vivo and the few clinical observations showed that Li-Fraumeni families were at a higher risk of secondary radio-induced malignancies.MethodsWe reviewed a cohort of patients with germ-line p53 mutations who had been treated for breast cancer as the first tumor event. We assessed their outcome and the incidence of secondary radio-induced malignancies.ResultsAmong 47 documented Li-Fraumeni families treated from 1997 to 2007 at the Institut Gustave Roussy, 8 patients had been diagnosed with breast cancer as the first tumor event. Three patients had undergone conservative breast surgery followed by postoperative radiotherapy and five patients had undergone a mastectomy (3 with postoperative radiotherapy). Thus, 6/8 patients had received postoperative radiotherapy. Median follow-up was 6 years. Median age at the diagnosis of the primary breast cancer was 30 years. The histological characteristics were as follows: intraductal carcinoma in situ (n = 3), invasive ductal carcinoma (n = 4) and a phyllodes tumor (n = 1). Among the 6 patients who had received adjuvant radiotherapy, the following events had occurred: 3 ipsilateral breast recurrences, 3 contralateral breast cancers, 2 radio-induced cancers, and 3 new primaries (1 of which was an in-field thyroid cancer with atypical histology). In contrast, only one event had occurred (a contralateral breast cancer) among patients who had not received radiation therapy.ConclusionsThese observations could argue in favor of bilateral mastectomy and the avoidance of radiotherapy.

Highlights

There are no specific recommendations for the management of breast cancer patients with germline p53 mutations, an exceptional genetic condition, regarding postoperative radiotherapy
Li-Fraumeni syndrome (LFS) is inherited in an autosomal dominant pattern with the frequent occurrence of soft tissue/bone sarcoma, breast cancer, leukemia, brain tumors and other cancers [1,2]
Germ-line TP53 gene mutations are mainly reported in LFS and approximately 250 distinct germ-line TP53 mutations have been described in the literature [4]

Summary

Introduction

There are no specific recommendations for the management of breast cancer patients with germline p53 mutations, an exceptional genetic condition, regarding postoperative radiotherapy. Li-Fraumeni syndrome (LFS) is a rare disorder that considerably increases the risk of developing several types of cancer, in children and young adults. Mutations in the CHEK2 gene have been reported in a few LFS and Li Fraumeni-like syndrome (LFL) families [6,7,8]. Wild-type p53 was identified as the first tumor suppressor gene. It is at the crossroads of the network of signaling pathways involved in the elimination and inhibition of abnormal cell proliferation designed to prevent neoplastic development [9,10]. We attempted to assess the incidence of radio-induced malignancies in a prospective cohort of families with germ-line p53 mutations, focusing on breast cancer occurring as the first malignancy

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Conclusion