Breast Cancer Patient with Li-Fraumeni Syndrome: A Case Report Highlighting the Importance of Multidisciplinary Management

Abstract

Germline mutations in TP53, a tumor suppressor gene, are involved in the development of Li-Fraumeni syndrome, a rare disorder that predisposes carriers to multiple tumors. TP53 mutations have been associated with resistance to treatment and poor prognosis. A young female with the pathogenic germline TP53 mutation c.844C > T (p.R282W) was diagnosed with two metachronous breast tumors, one HER2-negative and the other HER2-positive. She was later diagnosed with synchronous glioblastoma, epidermal growth factor receptor-mutated lung adenocarcinoma, and HER2-negative breast cancer metastases. The patient was treated with local therapies, including brain surgery and radiotherapy, lung surgery, and a bilateral mastectomy, as well as with targeted systemic treatment. She proved to be highly sensitive to systemic therapy, and 13 years after the initial diagnosis of breast cancer and 6 years after the diagnosis of the two new primary tumors and recurrence of a prior cancer, she is alive with an excellent performance status. This surprising positive evolution may well be partly due to the pronged multidisciplinary approach to managing her disease and her extraordinary response to treatment: the lung adenocarcinoma showed excellent response to erlotinib; the breast cancer responded extremely well to eribulin and pegylated liposomal doxorubicin; and the glioblastoma has remained in response to surgery and radiotherapy. Despite harboring a TP53 mutation and having multiple tumors, this patient has shown an unexpectedly favorable evolution. The coordinated participation of a multidisciplinary team and the patient's own extraordinarily high sensitivity to systemic treatment played a major role in this evolution.

First case of endometrial cancer after yolk sac tumor in a patient with Li-Fraumeni syndrome

“…The specific TP53 variant in this patient is that a cytosine-to-thymine transition leads to a missense arginine-to-tryptophan transition at amino acid 282 (p. R282W) within exon 8. The R282W germline variant has previously been observed in cohorts that tend to develop mixed adenoneuroendocrine carcinoma of the gallbladder and breast cancer [ 17 , 18 ]. The R282W variant has been regarded as a hotspot variant at both germline and somatic levels associated with poorer prognosis as compared to other pathogenic missense variants [ 19 ], this variant is included in the dbSNP database (rs28934574).…”

Li-Fraumeni Syndrome, A Rarity Among Rarities: A Case Report and Review of Literature

“…Li-Fraumeni syndrome (LFS; OMIM #151623) is a rare, aggressive, dominantly inherited cancer predisposition syndrome with high penetrance and wide clinical variability. Affected individuals could suffer from synchronous or metachronous multiple primary tumours at different sites of the body, and several members of the same family could also be affected [ 1 ]. The tumours most frequently associated with LFS are soft tissue sarcomas, breast cancer, brain tumours, osteosarcoma, leukaemia and adrenocortical carcinoma [ 2 ].…”