Several clinical characteristics may distinguish an inherited form of breast cancer. In general, these include an age of onset which is 10 to 20 years earlier than the average age of onset, bilateral breast cancer, an increased occurrence of a second breast cancer, male breast cancer, the occurrence of additional cancer diagnoses in a single individual or among close relatives, the occurrence of characteristic co-morbiditites which are associated with known genetic syndromes, and the occurrence of multiple affected family members from one lineage, maternal or paternal. In inherited forms of cancer, there is a loss of either the maternal or paternal allele within the egg or sperm from which an individual is conceived, thus every daughter cell thereafter has 'one hit' at this genetic locus.
Sporadic cancers begin with two normal copies of a cancer susceptibility gene.
This process requires more time and generally occurs only once in a single cell. Thus, the distintions of an inherited form of cancer are earlier age of onset, greater chance of a second primary cancer, and cancer developinbg in several tissue types. The distribution of tissues types at risk for cancer development may depend upon the gene involved and the function of its protein product. This model of carcinogenesis may apply for tumor suppressor genes and DNA repair genes. Both genes are extrememly large and complex.