Abstract
BackgroundApproximately 5-10% of breast cancers are hereditary. Among hereditary syndromes, Hereditary Breast and Ovarian Cancer Syndrome (HBOC) and Li-Fraumeni Syndrome (LFS) have received the most attention. HBOC is due to mutations in the BRCA1 and BRCA2 genes and is characterized by breast adenocarcinoma and/or epithelial ovarian carcinoma. LFS is associated with germline mutations in TP53; the most frequent cancer types associated with this syndrome are sarcoma, breast cancer, leukemia, brain tumors and adrenocortical carcinomas. Other cancers related to LFS are found at lower frequencies. In Brazil, especially in the southern part of the country, a specific mutation in the TP53 gene, TP53 p.R337H, occurs at a high frequency in childhood adrenocortical tumors. It has been proposed that this mutation increases breast cancer risk in southern Brazilian women.MethodsWe carried out a case-control study to determine the prevalence of the TP53 p.R337H mutation in 28 female cancer patients attended at the Cancer Genetic Counseling Service of the General Hospital of the University of São Paulo Medical School of Ribeirão Preto who fulfilled Hereditary Breast and Ovary Cancer Syndrome genetic test criteria compared to healthy woman (controls). TP53 p.R337H mutation status was determined using the High Resolution Melting (HRM) method, followed by DNA sequencing. Fisher’s test was used to compare the prevalence of TP53 p.R337H in the patient and control groups.ResultsTwo of the breast cancer cases (7.1%) and none of the controls carried the TP53 p.R337H mutation. At the time of the investigation, both cases fulfilled testing criteria for Hereditary Breast and Ovary Cancer Syndrome but not Li-Fraumeni or Li-Fraumeni-like Syndrome, based on genetic testing criteria of NCCN Clinical Practice Guidelines in Oncology (v.1.2010).ConclusionsWe suggest that genetic screening of Brazilian breast cancer patients who fulfill Hereditary Breast and Ovary Cancer Syndrome criteria and have a family history that includes other tumors of the LFS/LFL spectrum be tested for the TP53 p.R337H mutation.
Highlights
Her brother had Central Nervous System cancer at age 58. She did not meet the criteria for Li-Fraumeni Syndrome according to National Comprehensive Cancer Network (NCCN) Guidelines v.1.2010 [21] and v.4.2013 [14], because the tumors related to the Li-Fraumeni Syndrome spectrum, in this case breast and prostate cancer, were diagnosed in third degree relatives (Figure 2)
In the context of Hereditary Breast and Ovarian Cancer Syndrome (HBOC), she fulfilled the criteria of bilateral breast cancer personal history at any age, as two third-degree relatives were diagnosed with breast cancer (Table 2)
Based on our study, we suggest that TP53 p.R337H mutation prevalence in breast cancer patients suspected of HBOC in Ribeirão Preto, São Paulo, Brazil is high (7.1%)
Summary
5-10% of breast cancers are hereditary. Among hereditary syndromes, Hereditary Breast and Ovarian Cancer Syndrome (HBOC) and Li-Fraumeni Syndrome (LFS) have received the most attention. HBOC is due to mutations in the BRCA1 and BRCA2 genes and is characterized by breast adenocarcinoma and/or epithelial ovarian carcinoma. LFS is associated with germline mutations in TP53; the most frequent cancer types associated with this syndrome are sarcoma, breast cancer, leukemia, brain tumors and adrenocortical carcinomas. In Brazil, especially in the southern part of the country, a specific mutation in the TP53 gene, TP53 p.R337H, occurs at a high frequency in childhood adrenocortical tumors. It has been proposed that this mutation increases breast cancer risk in southern Brazilian women. About 5-10% of breast cancers are hereditary, and approximately 30% of young women who develop this type of cancer have a predisposition to disease [3,4,5,6]. The most frequent cancer types include sarcoma, breast cancer, brain tumors, leukemia and adrenocortical carcinomas. The NCCN Clinical Practice Guidelines in Oncology v.4.2013 take into account only classic LFS and Chompret criteria for LFS/LFL genetic testing [14]
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