New approaches to breast cancer treatment aim to say goodbye to chemotherapy

Q & A with Cancer Research Institute of Northern Alberta member John Mackey about leading clinical trials for breast cancer patients around the world.

Laura Vega - 1 November 2018

John Mackey, '90 MD, is working at the frontlines of translational cancer research. A medical oncology professor at the University of Alberta, Director of the Clinical Trials Unit at the Cross Cancer Institute (CCI) in Edmonton and member of the Cancer Research Institute of Northern Alberta (CRINA), Mackey is transforming research findings into health solutions for care―with an emphasis on finding new approaches to the treatment of different types and stages of breast cancer.

Q: Tell us about your work on breast cancer clinical trials.

One of our most successful team efforts has been building a global network of cancer researchers to address the most scientifically interesting clinical trials―those whose design is informed by our understanding of cancer biology.

I've been involved in Translational Research in Oncology (TRIO) since its origin in 1998 at the Cross Cancer Institute and I am one of its directors. TRIO is a not-for-profit organization that started out focused on breast cancer research, and then we found that some of the ideas we found in the laboratory that applied to breast cancer also applied to other cancers. So we had to expand our work because we go where the science drives us, but 85 per cent of the trials have been for breast cancer.

TRIO has now evolved to a cutting-edge organization running 40 studies in 34 countries, more than 350 cancer centres, nearly 40,000 patients on study and offices in Edmonton, Paris and Montevideo.

Q: Why did you decide to pursue cancer research?

I grew up on a farm in northern Alberta and I had a cousin with whom I was very close. She developed a rare form of cancer called hairy cell leukemia. She came to the Cross Cancer Institute and a doctor named Peter Venner treated her on a clinical trial. This was probably 40 years ago, and she's cured, she's alive and well today. I was a high school kid but I always wanted to be a physician, and even back then I thought, 'I'd be pretty cool if I could become a cancer doctor that tested new treatments.'

During medical school, I was inspired by my interactions with my professors, University of Alberta medical oncologists Peter Venner and Andy Belch, and medical researcher Lorne Tyrrell. I learned that we needed to do better for our patients, and understanding the biology of disease and testing new ideas in clinical trials was the only way to make progress, because we are all tired of seeing our patients die.

Q: How are these projects innovating breast cancer research?

We have a far more refined understanding of the biology underpinning cancer, and we finally have the tools to take advantage of the "weak links" in the abnormal biology. This means that the trials we are launching today are both more complex, and more likely to succeed.

We have about 15 breast cancer clinical trials underway right now. For a breast cancer patient coming to the Cross Cancer Institute, there are usually between 10 and 17 trials that are recruiting, which means they're open. We see patients in our practice and, if they're eligible, we try to get them on a trial, and that's why we have 750 patients per year on trials-on a per capita basis, that's the best in Canada.

Cancer research has never been as exciting. There are some really strong cancer researchers at the University of Alberta. We have an umbrella organization for all of them, the Cancer Research Institute of Northern Alberta (CRINA), and there are some really cool things going on here.

Q: How could all of this improve patients' lives?

The goal of virtually every cancer trial is to improve the length and/or quality of someone's life.

I've had the honour to work on trials spanning interventions as different as high dose chemotherapy and bone marrow rescue, physical exercise, nutritional supplementation, cancer vaccines, new gizmos to treat lymphedema (limb swelling after cancer treatment), caloric restriction, ways of improving communication in the clinic, and anti-cancer immune-boosting therapies.

Q: What do you consider to be the greatest progress your team has achieved in breast cancer research and treatment?

Three of our trials have been what we call registration trials. They're very strict, very carefully controlled and conducted trials that allow us to get regulatory approval for a new treatment. These are not small endeavours; often they involve anywhere from 700 to 3,000 patients and involve long-term follow-up, very careful attention to the side effects and close attention to the benefits.

I'm thrilled to say that these three clinical trials have led to Health Canada and Food and Drug Administration (FDA) approval of new breast cancer treatments-docetaxel and trastuzumab for early-stage breast cancer, and palbociclib for advanced breast cancer.

Q: What are the biggest challenges?

The biggest challenge ahead of us is figuring how to work around the ability of complex cancers to evolve resistance to everything we throw at it―ultimately, it is treatment resistance that means we can't cure these cancers. We need approaches that evolve in response to the changing biology of cancer cells under selective pressure.

Q: How do you envision the future of breast cancer diagnosis and treatment?

Cancer screening will be done with a single blood test, in which the DNA released into the blood by "popping" cancer cells is detected by characteristic, common mutations in the hotspots of the genome that drive most cancers. We will identify from the mutation pattern the most likely place that the cancer started, and only then go looking, for example, for a breast cancer with mammography or ultrasound.

Treatment will be individualized for each individual and each cancer.

We probably will always need surgeons to cut out most of the cancer cells, but we will then test the tumour to identify its unique biological signature, harvest our own immune cells and train them to attack our cancer, re-infuse our re-trained immune cells into the blood, where they eliminate any remaining cancer cells with virtually no side effects. These therapies have already been proven and are in early stages, but they might be accessible and cost-effective in the long run. At such a time, chemotherapy and radiotherapy would be obsolete, and they won't be missed.