The past few decades has seen great gains in breast cancer treatment.
As this evolution continues, the limbic spoke to the chair of the Scientific Advisory Committee of the Breast Cancer Trials Group, medical oncologist Associate Professor Prue Francis, about the latest developments in the treatment landscape.
What have been the biggest changes in the breast cancer treatment landscape over the past few decades?
In Australia the incidence of breast cancer continues to climb but the mortality rate is progressively decreasing, thanks to clinical trial research testing of new therapies and then implementation into routine management, in particular hormonal therapies such as tamoxifen and more recently aromatase inhibitors, and HER-2 targeted drugs like trastuzumab. Breast screening has also had an impact. If you look at what’s happened over the last three or four decades it is a good news story, but there is still work to be done. Breast cancer is incredibly common – about one in eight or one in nine Australian women will be diagnosed over their lifespan.
What are the next changes likely to be?
One of our focuses is trying to better tailor treatment to the individual, rather than having a one-size-fits-all strategy where every patient needs surgery, then chemotherapy and radiation and hormone therapy. Some of the future focus in breast cancer research is not just escalation of therapies in those with a higher risk situation, but also to identify lower risk situations that could perhaps have a de-escalation of therapy. We know that all these therapies can cause short term and long-term side effects and we are very conscious that while we are improving survival rates, we don’t want to leave those treated with additional health issues down the track. So, we are trying to work out who has a cancer that’s more likely to come back and might need treatment escalation, and who might have a breast cancer that is likely to have a favourable outcome, and therefore may be suitable for a de-escalation in therapies.
Are we at the point where there is enough evidence to support de-escalation?
Yes, that research trend started in recent years, for example Breast Cancer Trials launched a trial last year to identify a group of women 50 and older with favourable breast cancer – in this situation normally you would perform surgery and give radiation and hormone tablets. We are studying if we can we identify a group in whom we do not need to give radiation after surgery (EXPERT trial). Breast radiation usually takes about three to five weeks to deliver, and that’s a lot of visits to hospital, and some women have to travel long distances. We hope that this de-escalation strategy might be something that could be implemented into practice, but we need to show the safety of that approach in a randomised trial.
What are the challenges in researching the safety and effectiveness of de-escalation?
It is difficult research, novel treatments tend to attract more interest from funders. De-escalation perhaps isn’t exciting in that way, when it’s really about saying we are not trying to improve the cure rate, but to improve quality of lives, and that requires a large sample size and long follow-up to prove it’s safe in the short term and long term.
One trend we have seen in the last decade is more women when they are diagnosed wanting to have both their breasts removed, even when that’s not considered necessary by the treating team. I am not talking here about women with a BRCA gene mutation – the Angelina Jolie effect. It’s hard to know all the factors that are driving this – some of the gains in quality of life from showing we can do smaller surgeries with equivalent survival are being lost in some patients who just want both breasts removed.
Which new drug therapies are showing the most promise in treating breast cancer?
The federal government just funded [on PBS] a new category of agent, CDK4/6 inhibitors (ribociclib), from August 1, to be given in combination with an aromatase inhibitor for the first treatment of women with hormone receptor positive metastatic breast cancer. This is a tablet therapy that can be taken at home. This is an important development, thus far if you combine a CDK4/6 inhibitor with hormone therapy, it has been shown this lengthens the time that cancer can remain controlled, that’s been quite an impressive improvement, but we haven’t yet got the survival data. Another CDK4/6 inhibitor palbociclib is also being tested in the early breast cancer setting in a clinical trial by our Breast Cancer Trials group.
What about immunotherapies?
Roche’s IMpassion130 trial looks like it may prove game changing because this will be the first time in breast cancer in a randomised clinical trial that immunotherapy will be shown to benefit a group of women with triple negative breast cancer (TNBC) in this way.
The phase III multicentre, randomised, double-blind study is evaluating the efficacy and safety of atezolizumab and nab-paclitaxel compared with placebo in combination with nab-paclitaxel in 902 patients with locally advanced or metastatic TNBC who have not received prior drug therapy for metastatic breast cancer.
Metastatic triple negative breast cancer is considered an incurable situation. Roche’s recent press release indicates that the trial has met its primary endpoint which means they have been able to control the cancer for longer with the combination. So that’s going to be very big news when the results are formally presented. There have been some studies looking at immunotherapy in breast cancer, but this will be the first big study in triple negative metastatic breast cancer that is likely to report results.
This opens up the possibility that there may be a small subgroup who might perhaps be able to have longer term disease control. We don’t know if any can be cured, but it raises that possibility for the future. We obviously need to see the data to understand what is the magnitude of benefit, but these results ultimately might bring about a change in the way that triple negative breast cancer is managed in the first-line metastatic situation – it’s a kind of ‘watch this space’.
Professor Francis has received honoraria from AstraZeneca and Novartis for giving overseas lectures.
A/Professor Francis is part of the Breast Cancer Trials Group. The organisation is fundraising through the month of October. To donate or buy a Woman’s Health Diary with the money going towards funding for trials go to the website www.breastcancertrials.org.au