Abstract
BackgroundWomen with Li‐Fraumeni syndrome (LFS) have elevated breast cancer (BC) risk. Optimal BC treatment strategies in this population are yet unknown.MethodsBC subtypes and treatment were retrospectively investigated between December 2016 and January 2019 in a multicentre study. BC risks were evaluated according to the type of surgery.ResultsThirty‐five women of our study population (35/44; 79.5%) had developed 36 breast lesions at first diagnosis at a mean age of 34 years. Those breast lesions comprised 32 invasive BCs (89%), three ductal carcinoma in situ alone (8%) and one malignant phyllodes tumour (3%). BCs were mainly high‐grade (18/32), of no special type (NST; 31/32), HER2‐enriched (11/32) or luminal‐B‐(like)‐type (10/32). Affected women (n = 35) received breast‐conserving surgery (BCS, n = 17) or a mastectomy (ME, n = 18) including seven women with simultaneous contralateral prophylactic mastectomy (CPM) at first diagnosis. Nineteen women suffered 20 breast or locoregional axillary lesions at second diagnosis with mean age of 36. Median time between first and second diagnosis was 57 months; median time to contra‐ and ipsilateral recurrence depended on surgical strategies (BCS: 46 vs. unilateral ME: 93 vs. bilateral ME > 140 months). Women with a primary treatment of solitaire therapeutic ME suffered from contralateral BC earlier compared to those with therapeutic ME and CPM (median: 93 vs. >140 months).ConclusionAggressive BC subtypes occur among women with LFS. Surgical treatment, i.e. ME and CPM, may prolong time to a second BC diagnosis. Conclusion on long‐term survival benefit is pending. Individual competing tumour risks and long‐term outcomes need to be taken into consideration.
Highlights
Li-Fraumeni syndrome (LFS, MIM 151623) is a rare and highly penetrant cancer predisposition syndrome characterised by a broad cancer spectrum and caused by pathogenic/likely pathogenic (P/LP) germline variants in the TP53 tumour suppressor gene.1–4 Since TP53 is included on gene panels offered to women with suspected hereditary breast and ovarian cancer (HBOC), P/LP TP53 variant carriers are increasingly identified among women not meeting current LFS testing criteria.1–3,5 Given the fact that not all patients with LFS are being diagnosed the precise number is unknown
Based on published population prevalence estimates of TP53 germline variants, we estimate that the number within Germany is around 15000.6 P/LP in TP53 are detected in up to 7.7% of women with breast cancer (BC) younger than 31 and in
In case of BC, we considered contralateral prophylactic mastectomy (CPM) in case of first BC and secondary PM according to the patients choice due to the genetic test result or a second BC diagnosis
Summary
Li-Fraumeni syndrome (LFS, MIM 151623) is a rare and highly penetrant cancer predisposition syndrome characterised by a broad cancer spectrum and caused by pathogenic/likely pathogenic (P/LP) germline variants in the TP53 tumour suppressor gene.1–4 Since TP53 is included on gene panels offered to women with suspected hereditary breast and ovarian cancer (HBOC), P/LP TP53 variant carriers are increasingly identified among women not meeting current LFS testing criteria.1–3,5 Given the fact that not all patients with LFS are being diagnosed the precise number is unknown. Based on published population prevalence estimates of TP53 germline variants, we estimate that the number within Germany is around 15000.6 P/LP in TP53 are detected in up to 7.7% of women with breast cancer (BC) younger than 31 and in 50% by age of 70, typically diagnosed in women under the age of 31 and often occurs as synchronous bilateral or metachronous contralateral BC and comes with a general cancer risk of up to 100%.2,5,10,11,15–19 In case of a BC diagnosis under the age of 35, annual rates of contralateral BC are almost twice as high among women with LFS compared to female carriers of a P/LP variant in BRCA1 or BRCA2 (7.0% vs 3.6% or 2.6%).[17] Based on these BC risks and considering the risk for other LFS-a ssociated cancers such as sarcomas, adrenocortical carcinoma, brain tumours or leukaemia, international experts recommend a comprehensive cancer surveillance programme including annual whole body and breast magnetic resonance imaging (MRI).[20,21] In cancer-free women with LFS, bilateral prophylactic mastectomy (BPM) can be considered.
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