Cancer's Microenvironment

“Nobody ever died of breast cancer cells. Cells don’t kill you. Cells are only a problem if they form tumors,” explained Larry Norton, Deputy Physician-in-Chief for Breast Cancer Programs at Memorial Sloan Kettering, during a CancerSmart talk in March. And, he added, these cells are “only a problem if they form masses in organs and start to destroy the function of those organs.”

The real danger, Dr. Norton and the other panelists said, is found in the cancer cell’s microenvironment — conditions in the cell’s immediate surroundings that may allow it to survive, grow, and form tumors. “We like to think of cancer cells as criminals, but most criminals can’t commit a crime without some help,” said clinician-scientist Elizabeth Comen.

Studying the Breast Cancer Crime Scene (and Finding New Criminals)

Recently, scientists have begun to employ sophisticated genetic and molecular pathology techniques to scrutinize the tumor microenvironment and identify the proteins, genes, and other substances that assist cancer cells in their growth and spread.

With this approach, researchers are identifying new and different types or subtypes of breast cancer, allowing for improved or more-precise therapies. For example, breast tumors that depend on a steady supply of hormones such as estrogen and progesterone, which drive growth through hormone receptors, can be prevented or treated with various hormone-blocking drugs. Other tumors that may be stimulated by an excess of a receptor called HER2 can be treated with drugs that block this and related receptors.

But what about the cancers that lack all three of these important receptors? Doctors have had to rely on conventional chemotherapy to treat these “triple-negative” breast cancers, but the hunt is on for new targets that drive their growth so that additional treatments can be developed.

Accessories to the Crime

The causes of breast cancer can vary. Most breast cancers are spontaneous and related to aging, although some are caused by inherited mutations, such as in the BRCA1 and BRCA2genes. (Women with a strong family history of breast or ovarian cancer can talk to their doctor and to a genetic counselor to assess their risk and select the best method of preventing or treating breast cancer.)

For many breast cancers, the answer may lie in the tumor microenvironment. According toClifford Hudis, Chief of the Breast Cancer Medicine Service, energy imbalance (more calories, less exercise) is increasingly recognized as a risk for some breast cancers.

Inflammation is a key element of the microenvironment. Investigators recently learned that obesity — long associated with postmenopausal breast cancer and other malignancies — is a frequent cause of local, low-grade inflammation of fatty deposits, including in the breast itself. As fat cells die, they are removed by cells called macrophages that secrete inflammatory chemicals that prompt the body to produce estrogen. This may promote tumor growth, said Dr. Hudis, but it also offers an opportunity for treatment as well as prevention.

Bringing in the Police

Recent additions to the treatment arsenal are drugs that can increase the activity of the immune system and unleash it on cancer cells. The development of new breast cancer therapies may depend on our ability to enhance parts of the immune system that may be useful in fighting cancer cells, Dr. Hudis explained.

One promising approach is a new therapy called ipilimumab, currently approved for use in patients with melanoma. By blocking a substance called CTLA-4, the drug prompts the immune system to unleash a flood of powerful T cells capable of destroying cancer cells.

Doctors at Memorial Sloan Kettering are also studying the effectiveness of ipilimumab after cryoablation, a technique that involves freezing tumor tissue in order to stimulate the immune system.

Finally, in collaboration with Memorial Sloan Kettering scientists, Dr. Comen is evaluating an approach in which doctors may one day be able to remove a patient’s neutrophils (a type of white blood cell), increase their cancer-fighting capacity with growth factors, and later reintroduce them into the patient.

Watch the discussion, or explore further information on breast cancer.

http://www.mskcc.org/blog/breast-crime-scene-experts-discuss-where-we-are-today-and-where-we-re-headed