Key words

Germ-Line Mutation, Hyperlipidemias, Li-Fraumeni Syndrome


Li-Fraumeni syndrome (LFS;OMIM #151623) is a rare autosomal-dominant, inherited tumor predisposition syndrome associated with an increased risk of a variety of malignancies[1] that caused by heterozygous germline mutations in the TP53 gene and almost one third (15-35%) of cancer survivors with LFS will develop multiple primary cancers over their lifetimes.[2] Breast cancers in TP53 mutation carriers, recently, have more often been reported to be hormone receptor and HER-2 positive by immunohistochemistry, and most invasive ductal carcinomas in LFS are also hormone receptor positive and/or HER-2 positive.[3] Additionally, a study in 1999[4] and the other study in 2006[5] reported that P53 deficiency developed severe hyperlipidemias and atherosclerosis in vivo.

Case report

In December 2010, a 52-year-old woman referred to Clinic of Oncology, Kermanshah University of Medical Sciences, Kermanshah, Iran, with a pain in the left breast. She had no history of other breast complaints or surgeries. Her mother had breast cancer. Her father, brother, two sisters and Mother’s brother died due to hyperlipidemia complications (cardiovascular events). One of her other sisters had anti-phospholipid antibody syndrome (APLAS).Her blood group was AB+ . Pathology report showed that she had breast cancer (medullary carcinoma) and computed tomography (CT) scan showed no evidence of metastasis. Results of immunohistochemistry (IHC) for markers showed: ER, PR and p53 were positive, Her2 was 3 positive and Ki67 in 20% of cells. She did 4 courses of chemotherapy with doxorubicin plus cyclophosphamide (endoxan) and paclitaxel (300mg per day). Due to financial constraints, she couldn’t prepare trastuzumab (herceptin). She was then treated with radiotherapy (5000 CGY) for 25 courses. In October 2013, three years after first cancer diagnosis, her pathology report showed colon cancer (invasive adenocarcinoma). A tumoral lesion in distal part of rectum was evidenced by rectosigmoidoscopy and also CT that was identified a tumor with 10cmof anal verge in rectum. After sphincter sparing surgery, she was treated with six courses of chemotherapy with xeloda (capecitabine) + oxaliplatin. At now (May 2014), she is treating with hormone therapy for breast cancer with25 mg per day of aromasin (exemestane, an aromatase inhibitor).


Breast cancer is the most common tumor in women with LFS, an inherited cancer syndrome.[3]In our report, we describe a 52-year-old, woman patient with two tumors (breast + colon) with no metastasis based on clinical criteria. The markers of case presented herein (ER, PR, p53, Ki67 and HER-2 markers) were positive. In agreement with current study, recent reports [6],[8] suggest that LFS-associated breast cancers is both hormone receptor and HER-2 positive. Also, the other studies[9],[10] showed that breast cancer, in germline TP53 mutation carriers, is commonly HER-2 + (63- 83%).Moreover, results of Abrahams et al.[11]indicate that the ER response can possibly be employed as a prognostic marker to identify carriers in various hereditary cancerprone syndromes (such as Li-Fraumeni Syndrome) at an early age. A number of studies,[1],[3],[12],[13] and our knowledge of other study showd case reports of LiFraumeni Syndrome in patients with breast cancer that the onset age for the first tumor (age of first cancer diagnosis) is between 10 to 52 years but focuses on 20-40 years interval. We pointed out that father, brother, two sisters and Mother’s brother of the case died due to hyperlipidemia complications. It has been previously demonstrated that there are several common molecular pathways of disease pathogenesis in atherosclerosis and cancer [14]. Cell proliferation regulatory pathways including genes involved in the G1 to S checkpoint have been associated with plaque progression (atherosclerosis), stenosis and restenosis after angioplasty as well as in cancer progression[15] so that absence of p53 accelerates atherosclerosis by increasing cell proliferation in vivo.[4] The case presented herein shows an evident association between both hyperlipidemia complications and common diagnosed (breast) cancer and the patient’s family history. Our observations emphasize on previous reports that the role of p53 in atherosclerotic lesion development might be associated with its function in cell replication control.


Although modern treatments, such as those mentioned in this article, may result in improved outcomes for women with LFS-associated breast cancer, future emerging therapeutic strategies such as the new cell cycle and angiogenesis regulators may be simultaneously successful in blocking the development and progression of both LFSassociated cancer and atherosclerosis diseases.