Pathophysiology

Breast cancer is either invasive or noninvasive (often referred to as in situ).  There are two types of noninvasive breast cancers: ductal carcinoma in situ (DCIS) and lobular carcinoma in situ  (LCIS).  These two types of noninvasive breast cancers do not invade the basement membrane of the breast (see Fig. 1, Anatomy of the Breast).  As their names suggest ductal carcinoma in situ cancer cells are found in the lining of the duct whereas lobular carcinoma in situ cancer cells are found in the lobules (see Anatomy section for a detailed description of the ductals and lobules of the breast).

Breast cancer, like other cancers, occurs because of an interaction between the environment and a defective gene. Normal cells divide as many times as needed and stop. They attach to other cells and stay in place in tissues. Cells become cancerous when mutations destroy their ability to stop dividing, to attach to other cells and to stay where they belong. When cells divide, their DNA is normally copied with many mistakes.

 

Error-correcting proteins fix those mistakes. The mutations known to cause cancer, such as p53, BRCA1 and BRCA2, occur in the error-correcting mechanisms. These mutations are either inherited or acquired after birth. Presumably, they allow the other mutations, which allow uncontrolled division, lack of attachment, and metastasis to distant organs. Normal cells will commit cell suicide (apoptosis) when they are no longer needed. Until then, they are protected from cell suicide by several protein clusters and pathways.

One of the protective pathways is the PI3K/AKT pathway; another is the RAS/MEK/ERK pathway. Sometimes the genes along these protective pathways are mutated in a way that turns them permanently "on", rendering the cell incapable of committing suicide when it is no longer needed. This is one of the steps that causes cancer in combination with other mutations. Normally, the PTEN protein turns off the PI3K/AKT pathway when the cell is ready for cell suicide.

In some breast cancers, the gene for the PTEN protein is mutated, so the PI3K/AKT pathway is stuck in the "on" position, and the cancer cell does not commit suicide.

There are the two types of noninvasive  breast cancer described above and there are also two types of invasive breast cancer: infiltrating ductal carcinoma and infiltrating lobular carcinoma.  

As their names suggest, infiltrating ductal carcinoma penetrates the wall of the duct and travels to areas outside of it whereas infiltrating lobular carcinoma spreads through the wall of the lobule and also travels to areas outside of it.  Infiltrating ductal carcinoma is the most common type of breast cancer, accounting for between 70%-80% of the cases of breast cancer. 

Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure.

Failure of immune surveillance, the removal of malignant cells throughout one's life by the immune system.

Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells can facilitate malignant cell growth.In breast adipose tissue, overexpression of leptin leads to increased cell proliferation and cancer.

Breast cancer, like other forms of cancer, is the outcome of multiple environmental and hereditary factors. Some of these factors include:

1. Lesions to DNA such as genetic mutations. Mutations that can lead to breast cancer have been experimentally linked to estrogen exposure.
2. Failure of immune surveillance, a theory in which the immune system removes malignant cells throughout one's life.
3. Abnormal growth factor signaling in the interaction between stromal cells and epithelial cells can facilitate malignant cell growth.
4. Inherited defects in DNA repair genes, such as ''BRCA1'', ''BRCA2'' and ''TP53''. People in less-developed countries report lower incidence rates than in developed countries.