Breast cancer (BrCa) patients with Li-Fraumeni Syndrome (LFS) require customized clinical care, mainly due to elevated lifetime cancer risks that these patients face, as well as the diagnosis of secondary, radio-induced neoplasms. Preclinical data have shown that TP53 deficient cells are at increased risk of malignant transformation in the setting of ionizing radiation. TP53 pathogenic variants are strongly associated with very early onset, frequently HER2-amplified BrCa diagnosis.
In total, thirteen patients fulling clinical criteria for LFS and previously referred to the Molecular Diagnostics Laboratory of NSCR ‘Demokritos’ from 2005 to 2016, carried a pathogenic TP53 variant. Of these, twelve and one had been diagnosed with BrCa as the first and second tumor event, respectively. Eight of these were treated with total mastectomy without postoperative radiotherapy, while five were treated with lumpectomy plus postoperative radiotherapy. A loco-regional relapse was defined as an ipsilateral relapse in either the breast or lymph node bearing areas (axillary, internal mammary, supra-clavicular) or both occurring since the date of the diagnosis. Distant disease was defined as BrCa recurrences that were not in the contralateral breast nor in loco-regional areas. Radio-induced malignancies were defined as malignancies occurring in the radiation area.
Of the five patients who received postoperative radiation, four had a secondary, non-metastatic cancer diagnosis, summarizing a total of six events and more specifically, three were contralateral BrCa, one was a local relapse and two malignancies in other sites, of which one was a radio-induced lung cancer, developed at the site of the radiation area. On the contrary, a single event occurred among patients initially treated with total mastectomy without receiving postoperative radiation.
These data highlight the necessity of TP53 genetic testing, especially in young women diagnosed with BrCa, prior to treatment decision and are in accordance with published clinical observations and favor the avoidance of postoperative radiotherapy in breast cancer patients with LFS.
Hellenic Academy for Oncology.
Has not received any funding.
All authors have declared no conflicts of interest.