The 2012 CTRC-AACR San Antonio Breast Cancer Symposium, 4-8 December

Results of the TACT2 and BEATRICE breast cancer trials

Professor David Cameron – Edinburgh University, UK

Earlier on today I presented the results from the UK TACT2 trial which is an adjuvant breast cancer study we conducted in the UK. We enrolled just under 4,400 patients from 129 hospitals. It’s another example of being able to run a large trial across the whole of the UK, not just the academic hospitals. The hypothesis we were testing was that you may be able to deliver a more effective anti-cancer treatment for early breast cancer by giving part of your chemotherapy more quickly, what’s called accelerated. Traditionally we give chemotherapy every three weeks because we have to wait for the patients’ bone marrow, their blood count, to recover before we give the next dose of chemotherapy. One can give growth factors which mean that the blood count recovers more quickly and studies have been done with these growth factors showing that you can therefore give chemotherapy at a shorter interval, namely two weeks.

So we designed the trial to test that hypothesis with one particular drug called epirubicin. The disappointing thing about our trial was that we failed to confirm this hypothesis. We found, in fact, there was really no additional benefit in terms of preventing breast cancer recurrence for giving the chemotherapy at shorter intervals. What was interesting, however, was that we had expected around 20% of patients to have had a recurrence of their breast cancer by the fifth year of follow-up, in fact the figure was nearer 15%. So there is good news for patients in our study, there are fewer women recurring from breast cancer but we haven’t come up with a trick to reduce that number even further by giving chemotherapy at shorter intervals.

What happens next?

Not all women get the same chemotherapy, some women get a different chemotherapy. But from our point of view I don’t think we can see ways of further reducing the breast cancer recurrences by simply shortening the interval for chemotherapy delivery. It’s possible there might be a small group where it works but across the board we don’t see evidence for that. We’re going to need to look for further improvements through one of two routes. One route is to find newer agents that work more specifically against the biology of the cancer and obviously with drugs like Herceptin we’ve seen one of the avenues for this being a very successful approach but that only works in a subset of patients. I think the other direction where we may see improvement is by better targeting the drugs we do have to precisely the right patient population. Traditionally with chemotherapy you do not give a woman or a man with breast cancer just one chemotherapy drug; we give a cocktail of between two and four different drugs. If we could work out exactly which cancer really needed which drug you might be able to get further improvements with the same drugs by personalising or stratifying which person gets which particular drug.

Tomorrow afternoon I’m presenting the results of the BEATRICE trial. This is a trial that has been sponsored by Roche and run in almost forty countries around the world looking to see whether we can improve the outcomes for women with what’s called triple negative breast cancer. This is a subgroup of breast cancers which have only really been clearly described in the last five or eight years and we don’t have a specific targeted drug for them in the sense that we have Herceptin and some of the newer agents for women with HER2 positive breast cancer. So in a sense the women with triple negative breast cancer, the only option they have for drug treatment is chemotherapy and there is an association of a poorer outcome for women with this disease. There is evidence that these cancers may have increased angiogenesis, that is making new blood vessels to supply the cancers with oxygen and nutrients, and there is a drug which targets this called bevacizumab.

So the idea of this trial was to recruit women from around the world with triple negative breast cancer, give them conventional surgery, radiotherapy and chemotherapy and half of the women were randomised to get, in addition to all that, a year of treatment with the drug of bevacizumab. We report the results tomorrow morning but unfortunately we’ve not confirmed our hypothesis. We do not see a statistically significant improvement in the outcome of the women who got the bevacizumab as compared to those who don’t. I think we shouldn’t completely dismiss this possibility, there is some parallel biomarker data being presented tomorrow evening at a poster which suggests that there might be a subgroup where this drug could have an effect but it’s really only hypothesis generating.

However, I think there’s another important conclusion from our study. As I said a couple of minutes ago, triple negative breast cancer, if you look it up on the web, has a bad association. The messages that women bring into clinic are, “I’ve got a terrible cancer.” Actually our outcomes are a lot better than we had expected. Part of that reflects the patient population in that we had a majority of women with node negative triple negative breast cancer but nevertheless I will report tomorrow morning some of the best outcomes ever seen for triple negative breast cancer. And actually, therefore, for women who get this diagnosis they don’t need to be as scared as perhaps they would be if they went onto the web today and saw the current literature as to their predicted outcomes.

We have some way to go; we still need to find a way of targeting the specific and more aggressive biology of these cancers but it’s not quite such a bleak picture as we might have thought from the data of this randomised trial. It is a lot more work; the more we sub-classify breast cancer into different subtypes and try and work out precisely which treatment works for which breast cancer subtype. It’s been quite difficult over the years to do large trials in all early breast cancer patients; we’re getting better at that, we’ve now got to take that skill set and apply it to the question of smaller subgroups and for that I’m convinced we need to do international collaboration as we showed in the BEATRICE trial. Not everybody was convinced we could recruit 2,500 early triple negative breast cancer patients in a worldwide study; we did that in just over two years. I think therefore that if we end up with subgroups of breast cancers even down to 5-8% of all breast cancers we can, through international collaboration, run the studies. When it gets very challenging is if we were down to 1-2% of all breast cancer subtypes, then I think we really would have to think again carefully how we best do research in that area. But I think we’re getting better at collaborating internationally and that’s important for women.