The treatment of breast cancer has improved rapidly over the past two decades but it has also become more complex. Major research breakthroughs have given scientists a new understanding of the many factors that can cause breast cancer to develop and grow. This has also offered potential new ways to treat it.
Researchers now know that every patient’s cancer has a different genetic makeup. This complexity often makes finding the correct treatment more challenging. One approach is to customize or “personalize” treatment for each patient. This provides the patient with a treatment more likely to succeed and avoids giving treatments that might not work. It also has the benefit of sparing patients the side effects of those treatments. An example of a personalized treatment is the use of Trastuzumab (trade name Herceptin®), a drug used to treat HER2-positive breast cancer. HER2 is a protein that sits on the surface of the breast cancer cell and makes tumour cells grow faster. Twenty-five per cent of breast cancer patients have an increased amount of HER2 in their cancer. If these patients test positive for an increase of HER2, they are offered Herceptin. It works by attaching to the HER2 protein, halting the formation of new tumour cells and diminishing the amount of HER2 on the cells.
Herceptin is the focus of Dr. Raymond Reilly’s groundbreaking breast cancer imaging research. Dr. Reilly, a Professor and Associate Dean of Research at the University of Toronto’s Leslie Dan Faculty of Pharmacy, was looking for a way to measure the effects of Herceptin. “This project started with the idea that we wanted to develop imaging tools that could predict whether breast cancer patients who tested positive for HER2 would respond to treatment with Herceptin,” says Reilly.
“The drug is expensive, costing between $40- 50,000 per year to treat one patient. It also has some side effects and is effective in only one of two breast cancer patients,” Reilly says. “The current test for HER2, which is used to select patients who might benefit from the drug, doesn’t always predict which patients might respond to the drug.”
In a study funded by the Ontario Institute for Cancer Research (OICR) through its Smarter Imaging Program, Dr. Kristin McLarty, then a PhD student under Dr. Reilly’s guidance, found a way of using imaging with radiolabeled pertuzumab (trade name Perjeta®) to detect the effects of Herceptin on breast cancer tumours in animal models. Radiolabeled drugs are visible using certain imaging techniques, allowing doctors to trace their journey through the body and see where they end up. “Pertuzumab similarly attaches to HER2, but to a different region than Herceptin. We thought that if we could make pertuzumab into an imaging agent we could use it to see the effects of Herceptin on HER2 and the tumour.” The study proved it is possible to do so.
A pharmaceutical-quality version of the radiolabeled pertuzumab had to be produced to test its safety and effectiveness in humans. M.Sc. student Karen Lam spearheaded the two-year project as the research for her thesis. “I had to develop the formulation as well as all of the specifications and quality control tests for the product that will now be tested in patients,” says Lam. “We had to be sure that we could meet our strict specifications consistently.”
Dr. Reilly is now collaborating with Dr. Mark Levine, Professor and Chair of the Department of Oncology at McMaster University. Dr. Levine will lead a clinical trial of radiolabeled pertuzumab to test whether the imaging technology can predict whether Herceptin will work in patients. This is being made possible through funding from OICR’s High Impact Clinical Trials (HICT) Program. The three-year clinical trial will be coordinated by the Ontario Clinical Oncology Group at McMaster University. It will take place at the Juravinski Cancer Centre in Hamilton and at Sunnybrook Health Sciences Centre and at the University Health Network’s Princess Margaret Hospital in Toronto.
The trial will study 36 women with HER2-positive breast cancer, each receiving a low dose of radiolabeled pertuzumab. A nuclear medicine camera is used to measure the amount of radiolabeled pertuzumab localizing on the cancer. The injection of pertuzumab and associated imaging will be performed before starting Herceptin and then twice after treatment with Herceptin. The goal is to measure the shrinkage of the tumour to predict whether or not Herceptin has any effect
“We are in the final stages of preparing the documentation and expect it will be submitted to Health Canada for approval within the next few months,” says Reilly. “I believe we’ll be able to move forward with the clinical trial in 2013.”
It is not yet known if radiolabeled pertuzumab will be able to detect the effects of Herceptin in patients. But Drs. Reilly and Levine are optimistic. If successful, patients could have this kind of imaging study done to determine if they will benefit from Herceptin. It would spare them the side effects of unnecessarily undergoing a treatment that won’t be effective.
Reilly adds that none of this would have been possible without OICR. “We certainly wouldn’t be where we are today to embark on this trial without the support of OICR. OICR funded both Kristin McLarty and Karen Lam in their thesis research and is now funding the clinical trial. This was a unique situation in that this research was really conducted by two graduate students. The fact that OICR supports this says something about how the Institute sees the future of research and the training of future scientists.”
The opportunity to move this study to the clinical trial stage has led to collaborations with multiple cancer centres in Ontario. “Although we’re at an early planning stage, I suspect that we’ll be able to interact much more with these clinical centres going forward. It helps us appreciate the kinds of imaging tools that medical oncologists need to be most effective in treating patients,” says Reilly. Levine adds, “OICR has provided the unique opportunity for basic scientists and clinicians to work together. This will help us to bring new imaging technologies to the clinic and beyond.”