In the last few decades, marked advancement and progress were made in our understanding of molecular basis of breast cancer. Most investigators believe in a "two hit theory" for the causation of breast cancer in those women who have inherited a genetic defect. This means that although these women are born with a specific a genetic abnormality with high risk of breast cancer development, additional insults induced by the environment may be essential to cause the process of breast cancer development.

In early 1990s, researchers have discovered mutations for the gene that is responsible for p53 protein, (located on the chromosome 17) to be responsible for causing a syndrome called Li-Fraumeni syndrome. Li-Fraumeni syndrome is responsible for increased breast cancer risk, sarcomas and other tumor types. In 1997, genetic mutations in the PTEN gene, which is located on the 10th chromosome, have been shown to be linked to Cowden's syndrome. Cowden's syndrome is related to higher risk of developing breast cancer, and characteristic skin lesions. Cowden's syndrome is correlated with elevated risk of breast malignancy and skin lesions. Recently it has been shown that mutations involving STK11/LKB1 gene, which is located on the 19th chromosome, is linked to Peutz-Jeghers syndrome. This syndrome is associated with breast cancer, gastro-intestinal system cancers and hamartomas. Mutations in MLH1 and MLH2 are linked to Muir-Torre syndrome, which has been shown to be associated with elevated risk of breast cancer, genitourinary system and gastro-intestinal system tumors.

A major breakthrough in unraveling of the mysteries of breast cancer genetics was achieved with the identification of BRCA1 and BRCA2 also known as breast cancer associated gene 1 and 2. Identification and analysis of these two breast cancer associated genes had very significant impact on our understanding of breast cancer genetics.

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