Breast cancer and the immune system

Looking for a link

(November 26, 1998)
By Sharon Gray

What does the body's immune response have to do with breast cancer? There may be a connection that could have implications for the medical treatment of some breast cancer patients.

Dr. Sheila Drover, Medicine, is applying her specialized knowledge of the human immune system to determine just what that connection is.

It all has to do with human leucocyte antigens (HLA), which play a critical role in the regulation of the immune response to bacteria, viruses and tumour cells. There are more than 100 of these antigens, and one or more may be associated with a poor outlook for breast cancer patients.

Dr. Drover has done a lot of work on one particular antigen in this system, known as HLA-DR4. It's linked to many autoimmune diseases, such as rheumatoid arthritis.

Several years ago she came across some research in a Russian journal that associated HLA-DR4 with a poor prognosis in breast cancer patients. That immediately triggered her interest and, with the help of a Medical Research Foundation Grant from the Faculty of Medicine, her laboratory is now carrying out molecular typing of samples from the Manitoba breast tumour bank.
A method to extract and analyse DNA from these archival samples was developed with the help of graduate student Greg Butler, undergraduate medical student Peter Rogers and research assistant Ingrid Pardoe. Mr. Butler is also analysing the association of all different HLA-DR types with breast cancer, tumour size and lymph node status. When the analysis of all samples is completed, the association with the survival of the patient will be included.

"So far we've analysed about 80 of 200 samples," said Dr. Drover. "Although the preliminary data seems to indicate that HLA-DR4 is not associated with a poor prognosis for breast cancer, it does show an association of two other antigens HLA-DR11 and HLA-DQ3."

The difficulty in treating some types of breast cancer is that no one knows what the best treatment is for patients who are lymph node negative. Should they receive aggressive treatment like chemotherapy and radiation, or is it unnecessary? A specific HLA association with prognosis could indicate the appropriate treatment for these patients.

In October, Dr. Drover's project received $52,000 from the Canadian Breast Cancer Foundation. That's enough to keep it going while further funding is sought from Canadian Breast Cancer Research Initiatives.

Dr. Drover's research has wider implications in the field of breast cancer research.

"The literature is full of reports that say if a patient's cancer cells are expressing HLA-DR it's a sign of a good prognosis," she explained. "But that's looking at HLA-DR globally, and actually there are 16 groups with variations within each group. So it's a controversial finding."

Some of that controversy could be solved by analysing the expression of HLA-DR types in cancer cells, and that's what Dr. Drover's lab has begun to do. Graduate student Allison Edgecombe is working on HLA-DR expression in breast cancer cell lines, and her preliminary data shows that there is indeed differential expression of these molecules.

The work that Dr. Drover and her students are doing is pure, fundamental basic science. Very few breast cancer patients will ever hear about human leucocyte antigens, but someday some of them may benefit from the work done in a small immunology laboratory in Newfoundland.