What is cancer? Part 3

Cancer is a common problem. One in three of us will get a serious cancer. Although modern research has brought us a long way, cancer remains complex and difficult to understand - even for the experts - and there are still things to find out, which can be exploited.

Cancer is the only cause of death in Australia that is increasing at this point in time. There's active research going on, particularly in Victoria, which is a known centre for cancer research.

The work itself requires a lot of resources and a lot of collaborations; it's not a simple undertaking.

We are seeing in the whole of our population, the benefits of research. The mortality from breast cancer is falling, despite a steady increase in the number of cases that our community is experiencing. So the results are improving as a result of research. We can actually look you in the eye and say, ‘We are doing better'.

There's recently been a comprehensive review of outcomes in Victoria and we are by and large at world's best standards.

When I first started treating breast cancer, the expectation was that near half of the patients I saw would die. Over the last thirty years it's now down to around 20% of patients that present with breast cancer who will die of their disease. That is something that I don't need statistics and figures to understand, that is something that I can tell, in the clinic. It's a very dramatic change and a very important change.

Research now is not something that's just carried out in a laboratory. Here you see in the cartoon that's shown on the left, about cells dividing, is a particular attribute. If you increase the amount of something called HER2, you get more growth. More rapid growth. More invasiveness and more cancer-like behaviour of cells.

That could be all well and fine. It doesn't mean anything. Here in the clinic, if there is too much of this HER2 DNA and protein in cancer cells the patients will do worse. The patients with too much of the HER2 are the magenta line here and the patients with normal amounts in their tumours are in the upper line.

So this laboratory information appears relevant in the clinic. The information has translated from one place into another. If you create mice that have in the cells of their body, too much of this particular gene, too much of this particular protein, they get breast cancer.

The pearus strain of mice does not get breast cancer at all and by the time you reach 200 days more than 50% of the female mice, if you construct them so they have too much of this gene and too much of this protein, develop breast cancer.

So taking it back from a clinic to a laboratory, yes it still seems logical to continue to explore this phenomenon. What's this particular molecule called HER2? It's a signalling molecule. It signals across the membrane so it's one of the ways that messages can get from the outside world, out here, to the inside world here.

And it works because these molecules sit together as pairs, they chat together and sit together as pairs. They receive messages from the outside world and then send messages to the nucleus and make things happen.

You can imagine that if this is the normal distribution of these molecules on the surface of a cell and this is a normal amount of noise coming into a cell, just how much more noise and how much more of a message to grow there would be if you had a thousand-fold more of these molecules on the surface of the cell.

That's literally what happens, it's a bit like me going to your house and putting 999 extra letterboxes there. Harvey Norman would give you a very strong message to go and buy a new plasma TV - that's what happens to these particular cancer cells.

So here is how this signalling works. Receptors are activated on the outside of the cell and then you find the signal moving to the nucleus and the message here is growth, immortality (forgetting how to die) and the ability to move. All of those are the attributes of tumours. Growing faster, surviving longer and travelling to other places.

So the logic, at least from the biology, is this is something important in cancer. It's what we call an oncagene.

This other cartoon here shows you how this HER2 molecule is a very chatty girl. Her hand of friendship is always extended. And when one of her friends is activated with one of these growth factors - a bit perhaps like having a couple of drinks at a party - the two get together and they make a lot of chatter inside the cell. They send a very strong signal for the cell to grow and for the cell to exhibit malignant behaviour.

So we have an elegant construct that says this HER2 molecule is very important in the control of growth. We also know that about 25% of breast cancer cases have too much of this molecule in the cancer itself.

Is there a way ahead? Is there somewhere we can take this observation? The answer has been ‘Yes', and the first study was done adding an antibody that mopped up that receptor on the cell's surface. And you can see, with chemotherapy alone, particularly with this drug called Taxol, only 3% of the patients treated did not have progression of their cancer in one year. Only 3 in a hundred.

With the addition of Herceptin, that went up to 25, fully one quarter of patients did not have progression of their cancer.

This was the first proof that by manipulating this particular molecule, by attacking it or using it as a target, that research could actually now come back to the clinic and change what we do for patients.

Furthermore, and we're talking about metastatic breast cancer which is largely uncurable, the average survival or the median survival was pushed out by about 25% in the group of patients shown in the yellow, who received the Herceptin treatment rather than just chemotherapy.

Twenty five per cent, doesn't sound like a lot. Twenty-five months versus twenty months, does that sound like a lot? I can tell you if you have cancer or someone you love has cancer, that is a tremendous difference. This could be another wedding anniversary, it could be Christmas. It could be a child's birthday or a child graduating from nursing school.

Very important gains, particularly in the context of the twenty years we had not been able to budge these curves with anything that we did.