Research

Dr. Tak Mak, Director of the Campbell Family Institute for Breast Cancer Research, comments

Can the battle against breast cancer be won? Dr. Vincent Tuohy and his colleagues seem to think so with their ground breaking study in the June 10 issue of Nature medicine. This Ohio-based research group working out of the Cleveland Clinic has developed a vaccine that has been shown to inhibit breast cancer in mice genetically prone to the disease and thwart the growth of tumours in mice already inflicted with breast cancer. This is all well and good for mice, but can the same be true in humans? Dr. Tak Mak, Director of the Campbell Family Institute for Breast Cancer Research and Professor in the Department of Biomedical Physics at the University of Toronto provides his opinion.

What is the Breast Cancer vaccine?

The breast cancer vaccine targets a specific antigen, α-lactalbiumin, which is a protein only expressed in healthy women during lactation, but has been found at high levels in the majority of human breast cancers.

What are the risks associated with this vaccine?

The problem with developing a vaccine against a protein that is produced by the body naturally is the risk that the body’s immune system will attack its own healthy tissue. This would happen if a woman was vaccinated prior to her first full term pregnancy when lactation occurs. To escape this attack, women would have to be vaccinated when the antigen is not present, so well after her last full term pregnancy. If pregnancy was not an option, vaccination could conceivably occur during child bearing years, since women would not be lactating and therefore not producing the α-lactalbiumin protein.

There is also the presumption that α-lactalbiumin is expressed at high enough levels in human breast cancer for the vaccine to have an effect on tumour growth. If there is not enough α-lactalbiumin expressed in the breast cancer tumour then the vaccine would be ineffective.

If clinical trials are successful at what age would women get the vaccine?

Breast cancer occurs at the highest frequency when a woman has her first full term pregnancy late in life. This is best explained by the Pike hypothesis proposed by Malcolm Pike. Essentially, at menarche, which is a woman’s first menstrual cycle, there is a spike in estrogen. There is also a spike in estrogen during the third trimester of pregnancy. If the first full term pregnancy happens at 20, then the estrogen spike happens earlier in life and there is more time to decrease estrogen sensitivity before menopause where estrogen levels drop. If the first full term pregnancy occurs at 40, breast cells which are highly sensitive to estrogen will be exposed for an additional 20 years. Having low estrogen levels has been correlated with increased risk of breast cancer. To reduce the estrogen effect of breast cancer it is ideal to have a more gradual reduction in estrogen sensitivity, meaning more time between pregnancy and menopause. With this said, to avoid the immune system from attacking the healthy breast, yet still having effective breast cancer prevention properties, the vaccine would be most effective in women who are post child-bearing and premenopausal.

How often would a woman need to be vaccinated?

Vaccines are very unpredictable and the frequency of injection depends very much on the particular vaccine. A big part of antigen vaccination is whether your T-cells (a type of white blood cells that are the core of adaptive immunity) have seen the α-lactalbiumin protein before. Presumably, T-cells would not exist for this protein because it is produced by the healthy body during lactation. Therefore, regular boosting would be required to continually stimulate the immune response against this particular protein pathogen.

If the vaccine has a positive result in mice, can it be expected to have the same result in humans?

I can’t say, but I am actually skeptical because humans are so different from mice. There is the human- mouse difference and then there are the human differences from individual to individual. But this vaccine is definitely a step in the right direction.
A big part of antigen vaccination, which is even a problem for foreign antigens like viruses, is the adjuvant (an immunological agent that is often included in vaccines to enhance the recipient’s immune response). Alum, which is the only adjuvant approved for human vaccinations, is very poor. It is because we only have this one weak adjuvant that we do not have a vaccine for malaria, tuberculosis or HIV. Mice, which usually live in holes and eat bacteria and pathogens day in and day out, are less sensitive than humans, especially those in Western society who are so clean and are exposed to such little bacteria. Therefore, to stimulate the mouse immune system it has to be hit much harder. In this study the Freund’s adjuvant was used, which is at least 10 times stronger that alum. Alum itself would have little to no effect on mice.

Would this vaccine be effective in preventing male breast cancer?

It would depend on whether male breast cancer tumours have the α-lactalbiumin protein. The incidence of male breast cancer is less than 1% and of that 1%, 15% occur because there is a gene disruption in the breast cancer tumour suppressor gene BRCA2. Therefore, males who suffer from breast cancer have the genetic disposition to the disease and may not be helped by the vaccine.

Tags: Behind the Headlines, cancer, Health, Science, Tak Mak