The presence of a family history of breast cancer is a significant risk factor for the development of breast cancer. Although about 20–25 % of all breast cancer patients will have a family history of breast cancer, only 5–19 % of all breast cancer patients are likely to inherit an autosomal dominant high-penetrant gene for breast cancer.

BRCA1, BRCA2, T p53, and PTEN genes are some of the high-penetrant autosomal dominant inherited genes that are associated with breast cancer.

BRCA1 and 2 are tumor suppressor genes. They are involved with DNA repair of double-strand breaks by homologous recombination, transcriptional regulation, chromatin remodeling, and protein ubiquitination. The lifetime risk of developing breast or ovarian cancer in the mutation carriers varied from 35 to 85 % by 70 years of age.

BRCA 1 gene is a tumor suppressor gene located on chromosome 17q11. BRCA1-related breast cancers are high-grade, invasive cancers and are usually triple negative. Medullary and atypical medullary cancers are frequently associated and they exhibit histologic features like pushing margins, prominent lymphocytic response, syncytial growth pattern, and increased mitotic count.

BRCA 2 gene is a tumor suppressor gene located on chromosome 13q12. Germ line mutation in this gene confers a high risk for both male and female breast cancer, ovarian cancer, pancreatic cancer, and prostate cancer. BRCA2-associated breast cancers do not show any specific histopathologic subtype and are usually invasive cancers not otherwise specified. They tend to be ER and PR positive. The prognosis is similar to sporadic breast cancer.

Lifraumeni syndrome is a rare high-penetrant autosomal dominant germ line mutation of TP53 gene. It is located on chromosome 17p13.1 and it encodes for p53 protein. P53 is called the “guardian of the genome” as it is involved in cell cycle control and apoptosis. Patients with Li Fraumeni syndrome are susceptible for early onset breast cancer, soft tissue cancers, osteosarcomas, brain tumors, leukemias, etc. the incidence of breast cancer is about 50 % by the age of 40 years.

Cowden’s syndrome is caused by germ line mutation in the PTEN gene. It is tumor suppressor gene found on chromosome 10q23.3. This gene is associated with multiple pathways in the cell cycle. Cowden’s syndrome is associated with a high incidence of hamartomas in many organs and the lifetime risk of developing breast cancer is about 25–30 %. They are also susceptible for uterine and nonmedullary thyroid cancers and benign breast diseases like fibroadenomas.