Researchers have made a major breakthrough in finding out how aggressive cancers originate, raising hope of novel targeted therapies for future breast cancer patients, according to a study published in the peer-reviewed journal Cell Stem Cell. The scientists say this is the first study to show that the most aggressive cancers probably arise from intermediary, or progenitor, cells, which may significantly influence future research into fighting breast cancer.

Dr Matt Smalley, head researcher, from the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research, London, said:

These results represent a major advance in our understanding of breast cancer. It means we can now look very closely at where the disease forms and which genes are involved in that process. This knowledge will greatly improve the chance of finding effective new targeted treatments for breast cancer patients in the future.

Dr. Smalley and team gave laboratory mice the faulty BRCA gene, which is known to cause breast cancer. They then introduced the defective genes into the stem cells of one group of mice, and also into the intermediary cells of another group. The cancers which developed from the stem cells were different from those typically seen by those with the defective BRCA gene (inherited breast cancer).

The researchers were amazed to see that the cancer from the intermediary cells were nearly the same as those in triple negative breast cancer and forms of the disease which run in families. They concluded that these types of breast cancer originate in the intermediary cells.

The two most aggressive forms of breast cancer are precisely triple negative breast cancer and breast cancer caused by the defective BRCA genes, representing about 17% of the 46,000 reported breast cancer cases in the United Kingdom each year.

Triple negative breast cancer, for which there is no current targeted treatment, is more commonly found among young women, and women with African ancestry.

A promising targeted treatment for inherited forms of breast cancer, called PARP inhibitors, is undergoing clinical trials at the moment.

Professor Alan Ashworth, Director of the Breakthrough Breast Cancer Research Centre at the ICR, said:

Understanding the biology of breast cancer is essential for the future development of new ways to treat and prevent the disease. Our research gives a considerable new insight into how the disease forms and grows.

Adult stem cells replace normal functional cells when they die. Adult stem cells are long-lived cells which can divide many times.

Most cells in the body are usually fixed; they can only carry out specific functions, such as producing milk in the breast. Normal functional cells develop from stem cells – this occurs in stages through a series of intermediary (progenitor) cells. Most cells in the body are limited by the number of times they can divide.

Stem cells, unlike normal functioning cells, are long-lived and can divide many times. These two facts have led scientists to believe that they are the origins of several types of cancer. Many experts also believe that they may play a role in cancer treatment resistance.

Breast cancer is a tumor that has developed from the breast cells; the tumor has become malignant. A malignant tumor can spread outside the breast area, to other parts of the body – it has the potential to invade surrounding tissue. When cancer spreads beyond its point of origin, we call it “metastasis”.

A female breast consists of lobules – milk-producing glands. The breast is also full of ducts – milk passages that connect the lobules to the nipple. There is also fatty and connective tissue surrounding the ducts and lobules – this is called stroma.

The most common breast cancers start in the cells around the ducts. Others can start in the cells that line the lobules. More rarely, breast cancers can start in other parts of the breast. The human body has two ways of moving fluid about. One is through the blood stream, which carries plasma, red and white blood cells and platelets. Lymphatic vessels carry tissue fluid, waste products and infection fighting cells (immune system cells). Immune system cells are located in the lymph nodes – the nodes are shaped like a bean.

It is common for cancer cells to grow in the lymph nodes. They get there via the lymphatic vessels.

The lymphatic system of the breasts connect to the lymph nodes in three areas: Under the arm (axillary lymph node), in the chest (internal mammary node) and by the collarbone (supra or infraclavicular node).

Doctors guess that if cancer cells are in the lymphatic system, they are most likely to be in the bloodstream and will spread to other organs in the body. It is very hard to test for breast cancer cells in the bloodstream.

If breast cancer cells have got to the nodes under the arm (axillary), it will most likely swell. Whether or not it has swollen there, will decide what type of treatment a patient should have. If cancer cells are found in more lymph nodes, then the likelihood of it turning up in different parts of the body is greater. However, there is no hard and fast rule here. Women have had swellings in many nodes and did not develop metastases, while some women with no swellings in their nodes did.

“BRCA1 Basal-like Breast Cancers Originate from Luminal Epithelial Progenitors and Not from Basal Stem Cells”
Gemma Molyneux, Felipe C. Geyer, Fiona-Ann Magnay, Afshan McCarthy, Howard Kendrick, Rachael Natrajan, Alan MacKay, Anita Grigoriadis, Andrew Tutt, Alan Ashworth, Jorge S. Reis-Filho, Matthew J. Smalley
Cell Stem Cell, Volume 7, Issue 3, 403-417, 3 September 2010

Written by Christian Nordqvist