News

A Medical Vantage Point


It is our intention to provide a number of perspectives on the topic of breast cancer. Our ongoing partnership with the Cancer Research Center, State University of New York at Albany has provided a channel for sharing information pertinent to the frontiers of cancer research. To follow is an article written by Dr. Martin Tenniswood, Director, Cancer Research Center, Department of Biomedical Sciences, School of Public Health, State University of New York at Albany, Rensselaer NY. Those of you who attended our first Women’s Health Conference, December 2011 will recall Dr. Tenniswood as our keynote speaker.


Cancers develop because DNA (the genetic material) in individual cells accumulates mutations. These mutations can be caused by chemicals in our environment (often called carcinogens) or simply due to rare mistakes by the enzymes that copy the DNA during cell division. Nearly all cells in the body have enzymes that are responsible for making sure that the damage to the DNA caused by mutations is repaired. These DNA repair enzymes usually find and repair mutations before the DNA is copied when the cell divides. When the cells divide before the mutation is repaired, the mistake is copied into the DNA of the daughter cells, and can no longer be protected. 

Mutations that provide a growth advantage or survival advantage to the cell lead to the formation of a tumor. Some mutations cause the cells to grow faster than the normal, some of the mutations block the cells ability to die.  The first cells that accumulate DNA damage are often referred to as cancer stem cells (CSC) or tumor initiating cells (TIC). Ideally we want to find ways of preventing these cells from dividing so that the tumor does not develop. This area of research is referred to as chemoprevention.

 

The type of breast cancer and the subsequent treatment depends on the cellular origin of the cancer. The normal breast contains several different cell types: smooth muscle cells, basal epithelial cells and luminal epithelial cells. As is shown in the cartoon on the left, these cells are organized as ducts in the mammary gland. The major function of the luminal epithelial cells is to make the essential proteins and sugars in breast milk that are secreted into the duct. The smooth muscle cells and the basal cells also have very important support roles in making sure the luminal cells can perform this function during lactation. Mutations in any one of these cell types can lead to tumor formation, although most mutations occur in luminal epithelial cells and basal epithelial cells. The distinctions between luminal breast cancers and basal breast cancers are important because luminal breast cancer and basal breast cancers respond to different treatments. In general 60-70% of breast cancers are luminal type.  Most breast cancers initiated in the mammary ducts and in their early stages are called ductal carcinoma in situ (DCIS). As the tumors grow and become more aggressive they are classified as Invasive Ductal Carcinomas (IDC).

Based on histology (the way the tumors look under the microscope) breast cancers can be subdivided in many different types. However the histological characteristics alone are not sufficient to determine whether a particular type of tumor will respond to a particular treatment. Molecular techniques which examine the all the different proteins in the tumor (or all the different messenger RNAs in the cell that are used to make the proteins) can help to determine the best treatment for individual tumors. Some of the most important proteins in the different types of tumor are referred to as “marker proteins”.  The best known of these marker proteins is the estrogen receptor (ER), which is expressed in around 80% of luminal type breast cancers. Tumors that contain the estrogen receptor (ER+ breast cancers) are usually sensitive to anti-estrogen treatment, so drugs such as tamoxifen have been used with success. Aromatase inhibitors that prevent the tumor from making estradiol also prevent the tumors from growing. Tumors that contain the estrogen receptor usually also make the progesterone receptor, and are call progesterone receptor positive (PR+) tumors, and are usually very responsive to anti-estrogen and/or aromatase therapy.

Basal-like breast cancers usually do not have estrogen receptors, but a number of them make a protein that is called HER2/neu, or Heregulin. This marker protein is the target for the drug called Herceptin which blocks the growth of about 30% of basal-type breast cancers.

There are a number of tumors that do not make the estrogen receptor, the progesterone receptor or HER2/neu, and are referred to as triple negative breast cancer (TNBC). Development of treatments for TNBC is now a major research focus since there are fewer treatment options for TNBC than for ER positive or HER2/neu positive breast cancers.