EGFR-mutant lung adenocarcinoma in a patient with Li-Fraumeni syndrome

Abstract Germline mutations of TP53 are responsible for Li–Fraumeni syndrome in its 60–80%. We found a novel germline mutation, TP53: c.997del:p.R333Vfs*12 (NM_000546.6, GRCh, 17:7670713..7670713). The proband is a 40-year-old female, who was suffered from osteosarcoma in her right forearm at her age of 11. She was also suffered from lung adenocarcinoma in her right upper lobe and bone metastasis in her right scapula at her age of 37. She was treated with gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) because of EGFR mutation (L747-S752 del). Her bone metastasis became resistant after 1-year treatment. Bone metastasis had an additional EGFR mutation (T790M). The secondary treatment with osimertinib, an another EGFR-TKI, can successfully control the tumors for over 2 years. This TP53 mutation (R333Vfs*12) was first found in lung adenocarcinomas. The therapeutic effect of osimertinib for this triple mutant lung adenocarcinoma is better than the previous report.

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Lung Adenocarcinoma as Part of the Li-Fraumeni Syndrome Spectrum

JAMA Oncology ◽

10.1001/jamaoncol.2017.1358 ◽

2017 ◽

Vol 3 (12) ◽

pp. 1736 ◽

Cited By ~ 9

Author(s):

Olivier Caron ◽

Thierry Frebourg ◽

Patrick R. Benusiglio ◽

Stéphanie Foulon ◽

Laurence Brugières

Keyword(s):

Lung Adenocarcinoma ◽

Li Fraumeni Syndrome ◽

Li Fraumeni

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EFGR-mutant lung adenocarcinoma and Li-Fraumeni syndrome: Report of two cases and review of the literature

Lung Cancer ◽

10.1016/j.lungcan.2014.11.005 ◽

2015 ◽

Vol 87 (1) ◽

pp. 80-84 ◽

Cited By ~ 9

Author(s):

Charles Ricordel ◽

Marie Labalette-Tiercin ◽

Alexandra Lespagnol ◽

Mallorie Kerjouan ◽

Catherine Dugast ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Review Of The Literature ◽

Li Fraumeni Syndrome ◽

Li Fraumeni ◽

Syndrome Report

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

Case Reports in Oncology ◽

10.1159/000505684 ◽

2020 ◽

Vol 13 (1) ◽

pp. 130-138 ◽

Cited By ~ 2

Author(s):

Beatriz Cirauqui ◽

Teresa Morán ◽

Anna Estival ◽

Vanesa Quiroga ◽

Olatz Etxaniz ◽

...

Keyword(s):

Breast Cancer ◽

Lung Adenocarcinoma ◽

Tp53 Mutation ◽

Systemic Treatment ◽

Pegylated Liposomal Doxorubicin ◽

Bilateral Mastectomy ◽

Primary Tumors ◽

Multiple Tumors ◽

Li Fraumeni Syndrome ◽

Li Fraumeni

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.

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Fourth Primary Malignant Tumor in a Patient with Possible Li-Fraumeni Syndrome: Synchronous Diagnosis of Postirradiation Sarcoma, Cutaneous Relapse of a Previous Soft Tissue Sarcoma, and Lung Adenocarcinoma

Case Reports in Orthopedics ◽

10.1155/2014/597207 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6

Author(s):

Feridun Yumrukçal ◽

Yalin Dirik ◽

Arda Çinar ◽

Levent Eralp

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Lung Adenocarcinoma ◽

Young Patient ◽

Malignant Tumor ◽

Malignant Tumors ◽

Rare Entity ◽

Li Fraumeni Syndrome ◽

Li Fraumeni ◽

Postirradiation Sarcoma

We present a 46-year-old female patient who is diagnosed with synchronous postirradiation sarcoma, cutaneous relapse of a previous soft tissue sarcoma, and lung adenocarcinoma. More than one malignant tumor at the same time with an accompanying relapse of a previous malignant tumor is a rare entity. A relatively young patient diagnosed with adenocarcinoma of the urethra before age 40, which is an unusual tumor for that age, later three more different malignant tumors being diagnosed, two of which are synchronous, causes the suspicion of Li-Fraumeni syndrome.

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Successful treatment of a patient with Li–Fraumeni syndrome and metastatic lung adenocarcinoma harboring synchronous EGFR L858R and ERBB2 extracellular domain S310F mutations with the pan-HER inhibitor afatinib

Cancer Biology & Therapy ◽

10.4161/cbt.29173 ◽

2014 ◽

Vol 15 (8) ◽

pp. 970-974 ◽

Cited By ~ 5

Author(s):

Yuxia Jia ◽

Siraj M Ali ◽

Shumaila Saad ◽

Courtney A Chan ◽

Vincent A Miller ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Successful Treatment ◽

Extracellular Domain ◽

Li Fraumeni Syndrome ◽

Metastatic Lung ◽

Li Fraumeni

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Li-Fraumeni syndrome and adrenal tumours: case report

Endocrine Abstracts ◽

10.1530/endoabs.56.p101 ◽

2018 ◽

Author(s):

Mariana Tome ◽

Jessica Guarino ◽

Marta Iturregui

Keyword(s):

Case Report ◽

Li Fraumeni Syndrome ◽

Adrenal Tumours ◽

Li Fraumeni

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Neuroradiology Manifestations of Li-Fraumeni Syndrome: Epidemiology, Genetics, Imaging Findings, and Management

Neurographics ◽

10.3174/ng.2000003 ◽

2020 ◽

Vol 10 (4) ◽

pp. 228-235

Author(s):

S. Naganawa ◽

T. Donohue ◽

A. Capizzano ◽

Y. Ota ◽

J. Kim ◽

...

Keyword(s):

Cell Cycle ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Soft Tissue Sarcomas ◽

Suppressor Gene ◽

Imaging Findings ◽

Li Fraumeni Syndrome ◽

Increased Risk ◽

Li Fraumeni ◽

Risk Of Cancer

Li-Fraumeni syndrome is a familial cancer predisposition syndrome associated with germline mutation of the tumor suppressor gene 53, which encodes the tumor suppressor p53 protein. Affected patients are predisposed to an increased risk of cancer development, including soft-tissue sarcomas, breast cancer, brain tumors, and adrenocortical carcinoma, among other malignancies. The tumor suppressor gene TP53 plays an important, complex role in regulating the cell cycle, collaborating with transcription factors and other proteins. The disruption of appropriate cell cycle regulation by mutated TP53 is considered to be the cause of tumorigenesis in Li-Fraumeni syndrome. Appropriate surveillance, predominantly by using MR imaging, is used for early malignancy screening in an effort to improve the survival rate among individuals who are affected. Patients with Li-Fraumeni syndrome are also at increased risk for neoplasm development after radiation exposure, and, therefore, avoiding unnecessary radiation in both the diagnostic and therapeutic settings is paramount. Here, we review the epidemiology, genetics, imaging findings, and the current standard surveillance protocol for Li-Fraumeni syndrome from the National Comprehensive Cancer Network as well as potential treatment options.Learning Objective: Describe the cause of second primary malignancy among patients with Li-Fraumeni syndrome.

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