Breast Metachronous Carcinoma and Sarcoma in a Young Patient Leading to the Diagnosis of Li-Fraumeni Syndrome

Abstract

Breast cancer is the most frequently diagnosed malignancy and the leading cause of death in women [1]. A small portion of cases occur in young patients with 6.6% of all cases diagnosed below the age of 40 years, 2.6% below the age of 35 years and 0.65% below the age of 30 years [2]. Genetic and familial cancer syndromes are more prevalent in young patients compared to older counterparts. BRCA1 and BRCA2 mutations account for about 10% of all breast cancer cases in young women. Nevertheless, very early onset breast cancer might be the initial presentation of Li-Fraumeni syndrome (LFS). LFS is also known as sarcoma, breast, leukemia and adrenal gland (SBLA) cancer syndrome and is caused by the germline mutation of the TP53 gene, responsible for a wide spectrum of early-onset malignancies [3]. Its transmission is autosomal dominant with a prevalence of around 1/100000 in the general population and 1% of all breast cancers. Half of affected women will develop a cancer by the age 30 and the penetrance of the germline TP53 mutation reaches 100%. Breast cancer is the most common adult malignancy among patients with LFS [4]. Throughout this case report, we aim to illustrate clinical history and special considerations once the diagnosis of Li-Fraumeni syndrome is made. Case Description A 25-year-old primipara patient presented in May 2015 with a high grade invasive ductal carcinoma of the left breast (cT-2N1aM0). The hormonal receptors were positive, HER2/neu was amplified, and Ki-67 was expressed in 30% of tumor cells. She underwent anthracycline-based neoadjuvant chemotherapy with Trastuzumab and subsequently breast-conserving surgery with complete axillary lymph node dissection (ypT1bN0). The patient received adjuvant breast and axillary irradiation (64Gy), postoperative Trastuzumab and hormonal therapy by Tamoxifen and LHRH agonist. The patient's mother was diagnosed with breast cancer at age 44. Genetic testing for BRCA1 & 2 mutation was negative (Figure 1).