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ESMO Breast 2021 | Emerging treatments for breast cancer with brain metastases

Ahmad Awada, MD, PhD, Institute Jules Bordet, Brussels, Belgium, outlines the challenges of treating patients with breast cancer and brain metastases, in particular patients with triple-negative breast cancer (TNBC) and HER2+ breast cancer. Dr Awada comments on the role of tucatinib, a tyrosine kinase inhibitor, gives an overview of the epidemiology of breast cancer with brain metastases, highlighting the use of antibody therapies in the adjuvant setting, and discusses the impact of the blood-brain barrier and the brain microenvironment on brain metastases treatment. This interview took place at the virtual European Society for Medical Oncology (ESMO) Breast Cancer Congress 2021.

Transcript (edited for clarity)

Brain mets is a major problem in breast cancer, in metastatic breast cancer in particular. In triple-negative breast cancer as well in HER2-positive breast cancer. But I can tell you also for patient with luminal disease, hormone receptor-positive, in late evolution of the disease this problem is also a major issue for our patients. So, in general, that’s really a major issue. And we need to have found, providing solution for this problem...

Brain mets is a major problem in breast cancer, in metastatic breast cancer in particular. In triple-negative breast cancer as well in HER2-positive breast cancer. But I can tell you also for patient with luminal disease, hormone receptor-positive, in late evolution of the disease this problem is also a major issue for our patients. So, in general, that’s really a major issue. And we need to have found, providing solution for this problem.

So, the aim of my talk is to speak, let’s say emerging therapies in the management of brain mets from breast cancer. But as you know, probably the advances are mainly seen in HER2-positive breast cancer and much less in other tumor types. So, my presentation will not be really, unfortunately because there are not many advances now in the therapy of brain met outside HER2-positive breast cancer, with recent development of tyrosine kinase inhibitor, in particular the arrival of tucatinib. But fortunately have the breast cancer that are [inaudible] specific, to my knowledge, to the brain, and hormone receptor-positive, there are the very limited data, for example in CDK4/6 inhibitors. So, we are far from finding, let’s say, therapies for brain met, systemic therapy specifically.

Yeah, so my talk will be divided in two part. Of course I will go very quickly on the epidemiology, because even at the epidemiology level we are not confident with the available data about the incidence of this problem, because some of the active drug in breast cancer move to the neoadjuvant or adjuvant setting, and I’m thinking to immunotherapy in triple-negative breast cancer, which are not yet reimbursed but administered in the neoadjuvant setting, T-DM1 in residual disease and HER2 disease, pertuzumab, trastuzumab. So, there are some of the therapy use- T-DM, some of the therapy used in the mets study move to the adjuvant setting, and we don’t know exactly when the patient recur, what will be the recurrence and if the incidence of a brain mets is the same.

So, that’s what I would like to say about epidemiology. So, it’s important to have the clear idea today, because the things could be changed since the move of active drug to the early setting. I think it’s important in addition to when you think about therapy, there are two things here and two problem here in relation to brain met. There are what’s called the blood-brain barrier, okay? There are also the problem of the microenvironment in the brain. And in my opinion, the blood-brain barrier is one issue, but not the whole issue in relation to brain met. Because for years and years, we spoke about this blood-brain barrier which involve the active drug to pass the blood-brain barrier and so on. But consequently, the cancer cell on the brain are not, let’s say, exposed to high concentration of active drug there.

That could be a problem. But in my opinion, cancer cell on the brain, the behavior at the molecular level, at the genomic level is probably also different. Due to the microenvironment which is completely different in the brain compared to the lymph node, compared to the lung, compared to the bone. And so, our understanding of the microenvironment of the brain around the cancer cells there could lead to develop some specific target for systemic therapy of brain met. And so, this is a huge topic of, let’s say basic and mainly translational research.

Third, of course when we have brain met, and before to have brain mets, I think one major question is could we predict who will develop brain met in triple-negative breast cancer or HER2-positive breast cancer? Because we know 50% of these patients will develop brain met, but 50% will not develop brain met. And the question, why we are looking, and we should look to predictive biomarker. It could be clinical; it could be genomic biomarker to try to predict who will develop brain met? If so, we could approach the problem by what’s called primary prevention. So that’s a huge topic, the trial from to be well elucidated.

Now when the brain met will develop, we have the multidisciplinary approach – surgery, radiation, ablation, surgery [inaudible] and more recently at least with HER2-positive breast cancer systemic disease. And so, the disease to some extent is controlled by, around the brain of course, it’s controlled to some extent by this multidisciplinary approach. In my opinion one major question that could be, “Okay, if the patient will develop the first event in the brain, how we can prevent the second event and subsequent event?” What I call secondary prevention approach, and so that is really an interesting topic for clinical research.

So, in summary, at this level, so my presentation, unfortunately I do not have a lot of new drugs to teach on during this educational session. But probably what I will do, and I will do is to ask a lot of the important question in relation to brain met, and propose some, let’s say, kind of solution, at least to understand better the problem and to see how we can improve the outcome of our patient.

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Disclosures

Ahmad Awada, MD, PhD, has participated in an advisory role, has received institutional research grants, or has received speakers fees from Roche, Lilly, Amgen, EISAI, BMS, Pfizer, Novartis, MSD, Genomic Health, Ipsen, AstraZeneca, Bayer, Leo Pharma, Merck and Daiichi.

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