WIN 2016
Personalising breast cancer therapy
Dr Funda Meric-Bernstam - University of Texas MD Anderson Cancer Center, Houston, USA
Today, or tomorrow actually I guess, we’re talking about personalised cancer therapy and focussing on breast cancer. Although in general I’m a very positive person, the talk focusses on some of the challenges of personalised cancer therapy in breast cancer. We all have a lot of enthusiasm for personalised therapy, there’s quite a bit of buzz and hope, but there’s clearly some hype and unrealistic expectations so I think it’s very important to recognise the challenges so we can address those in our clinical trial designs as well as our day to day clinical practice and in patient interactions.
When we talk about precision medicine we’re talking about multiple facets of this and for breast cancer all of these areas are rapidly evolving. There is, of course, a tremendous amount of momentum already surrounding cancer risk prediction as well as how we can select patients better for preventive strategies. Of course with the advent of next generation sequencing there is a lot of momentum regarding multiplex testing for not single genes but a variety of genes with different risk implications. There’s a lot of momentum in the prognostic area especially for adjuvant therapy. But the area in our own programme we’ve been primarily focussed on is cancer prediction for therapeutic sensitivity.
We’ve had a lot of emphasis both at our own institution, at MD Anderson, as well as in other institutions looking at genomics in this arena, partly because it has been the low-lying fruit. Although I think we’re all recognising that diseases like breast cancer are multifactorial and even those patients that have a genomic driver have multiple genomic alterations and how we can bring that to therapeutic effect has been somewhat challenging. We’ve definitely had some promising hits like alterations like, HER2 are very compelling. In contrast we’re still trying to figure out how we can best leverage other findings like mutations which we recognise are common and have significant prognostic relevance.
One of the approaches that we’ve taken is also to try to explore trying to make decisions in the neoadjuvant therapy setting. The neoadjuvant therapy platform probably has been best developed for breast cancer where the goal in part is to try to cause downsizing, down-staging, of the tumour, looking at are there therapies that we can add or substitute to get higher rates of complete pathological response. In many tumour types there have already been successes where combinations with novel therapies have had a signal of efficacy and in our institutional programme, the MD Anderson Moonshot programme, there has been emphasis in the triple negative breast cancer scenario where we are looking at patients that are resistant to the standard neoadjuvant therapies and then patients are allocated in different treatment algorithms based on both molecular characteristics as well as really capitalising on opportunities for new, emerging therapies. It’s a very exciting programme that’s led by Dr Stacy Moulder in collaboration with Dr Fraser Symmans from Pathology where each treatment arm is led by a different investigator. So that makes a group team science approach and it will give us the opportunity to identify whether new therapeutics will be more effective than the existing therapies in patients where we don’t expect them to have significant response because patients that are more resistant already to the initial treatment regimen are being allocated to these treatments.
We are also using this to learn more about the biology, not only looking at predictors of response but also looking at the residual disease. We’ve had an ongoing programme looking at molecular characterisation of tumours that have not responded to chemotherapy, not just doing observational work but also generating patient derived xenografts. Patient derived xenografts are an emerging area where there’s a lot of excitement because we feel that maybe PDXs developed are a little more reflective of the heterogeneity in tumours that we see in humans. So that’s where by doing molecular characterisation of PDXs we can better look at novel therapeutics to identify more effective regimens.
At what point does treating a patient in an extremely personalised way become impractical vis-à-vis a broader approach?
That’s an excellent question and in a recent paper we published actually we looked at the genomic profile of serious triple negative breast cancer patients and every patient had a unique genomic profile. If you start thinking of it that way, clearly it demonstrates the challenge. But I do believe that clearly to bring treatments to bear we need to look at combinatorial therapies and we need to have safety data for the combinations. So likely for these patient populations there is going to be a handful of key combinations that will be effective, or that’s what we’re all hoping to identify.
Is there anything you would like to add?
I think this is a great time for institutions, both academic as well as commercial, to work together in partnership, of course, with our patients to really enhance clinical trial accrual and to have greater access to the opportunity to do combination therapies.
