Breast cancer (referring to mammary carcinoma, not mammary sarcoma) is histopathologically and almost certainly etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement.
Breast cancer remains the most common malignancy in women worldwide and is the leading cause of cancer-related mortality. More than 1-2 million cases are diagnosed every year, affecting 10-12% of the female population and accounting for 500 000 deaths per year worldwide. Approximately 5-10% are thought to be inherited. The hereditary breast cancer syndrome includes genetic alterations in various susceptibility genes such as p53, PTEN, BRCA1, and BRCA2. Sporadic breast cancers result from a serial stepwise accumulation of acquired and uncorrected mutations in somatic genes, without any germline mutation playing a role. Oncogenes that have been reported to play an early role in sporadic breast cancer are MYC, CCND1 (Cyclin D1) and ERBB2 (HER2/neu). In sporadic breast cancer, mutational inactivation of BRCA1/2 is rare. However, non-mutational functional suppression could result from various mechanisms, such as hypermethylation of the BRCA1 promoter.