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Eva Grunfeld, a physician scientist with the Ontario Institute for Cancer Research (OICR).

Decades of breast cancer research certainly tell a compelling success story. According to the Canadian Cancer Society, the death rate from the disease has dropped by more than 35 per cent since 1950, the lowest it has ever been. Through advances in screening, diagnosis and treatment, almost 90 per cent of women diagnosed with breast cancer today will be long-term survivors.

Yet the incidence of breast cancer has not changed over the past 60 years; one in nine women is still expected to develop the disease during her lifetime. In 2013, an estimated 23,800 Canadian women will be diagnosed.

"The continued high incidence, coupled with improved survival rates, means hundreds of thousands of women in Canada have had a breast cancer diagnosis at some point in their life," says Sandra Palmaro, co-CEO of the Canadian Breast Cancer Foundation. "The quality-of-life and research challenges associated with these numbers are huge in terms of treatment and post-treatment side-effects, and supporting these women's medical, psycho-social and other needs."

Researchers are continuing their efforts to further reduce mortality from breast cancer – which remains the second-leading cause of cancer-related deaths among Canadian women – but new priorities are emerging.

"Now that we know that the majority of women diagnosed with breast cancer will not die from the disease, we have started to concentrate more on 'survivorship,' rather than just 'survival,'" says Eva Grunfeld, a physician scientist with the Ontario Institute for Cancer Research (OICR).

Improving survivorship is a complex and multi-faceted goal, Grunfeld explains. "One area is follow-up care. We need to better understand the optimal frequency of follow-up visits and improve testing to provide the most appropriate care to cancer survivors. Another key focus is on reducing the negative impacts of the treatments themselves."

Newer chemotherapy treatments, for example, are more effective, but in many cases are also more toxic.

"Initially, to save lives, we took somewhat of a 'cure at any price' approach," says Monika Krzyzanowska, a medical oncologist and the clinical lead for quality care and access at Cancer Care Ontario (CCO). She and Grunfeld have collaborated on a number of research projects related to treatment effects.

"More recently, we've focused on figuring out how to minimize the side-effects or complications of these therapies that are so effective in making the cancer go away, as well as trying to determine what level of treatment different individuals need," Krzyzanowska notes.

One of the  long-term complications that researchers are working on is lymphedema, the sometimes significant and painful swelling in the arm and chest that can occur after the surgical removal of lymph nodes, as well as radiation treatment. Other research focuses on what has been called "chemo fog," the possibility that chemotherapy can impair cognitive functioning among patients in the longer term.

Grunfeld and Krzyzanowska are  currently researching the "acute toxicities" associated with chemotherapy. This work, supported by both the OICR and CCO, includes analysis of Ontario health-care data for women being treated for breast cancer between 2007 and 2009.

"We found that almost one of every two women receiving chemotherapy for breast cancer went to a hospital emergency department at least once during their four to six months of treatment, and a sizable proportion went several times," Krzyzanowska says. "Researchers, policy-makers and providers were equally surprised by this finding."

Common reasons for these visits included problems with fever and low white blood cell counts, which can lead to infection, and other chemo side-effects, such as serious nausea and vomiting.

"The next phase is to test more proactive approaches to helping women manage their symptoms before they need to go to the hospital," says Grunfeld. The interventions that are to be studied include one where cancer-centre nurses phone patients to check on their symptoms and help with management, and a second that involves an online information-sharing tool for patients and physicians.

This research and other projects hold much promise for improving the health and quality of life of Canada's growing numbers of breast cancer survivors. "Another emerging research priority is in the area of prevention," says Palmaro. "It's estimated that one in three breast cancers can be prevented. We need to learn more about how – and share this knowledge with women."

PROGRESS


Research seeks to reduce over-treatment by identifying risk of invasive breast cancer

Expanded screening through mammograms means that invasive breast cancer is being detected at earlier stages and more lives are being saved. Yet the diagnosis of early, non-invasive cancer is also increasing, presenting a challenge for women and their physicians in terms of how aggressively to treat disease that will likely remain benign.

Dr. Eileen Rakovitch, Sunnybrook Health Sciences Centre


Eileen Rakovitch, medical director of the Louise Temerty Breast Cancer Centre in Toronto and a radiation oncologist/scientist at Sunnybrook Health Sciences Centre, clearly understands this challenge. She treats many patients for ductal carcinoma in situ (DCIS), an early form of non-invasive cancer inside a milk duct in the breast.

"Women diagnosed with DCIS have excellent long-term survival rates and, without treatment, most patients would never develop invasive cancer, but 10 to 15 per cent will," explains Rakovitch. "Because we can't identify who's at highest risk, everyone gets treated – many of them unnecessarily.

Treatment usually involves surgery to remove the abnormal tissue while conserving the breast, often followed by radiotherapy. Several clinical trials have shown that women who have surgery and radiation have a lower risk of going on to develop invasive cancer than those who have surgery alone. About one-third of women with DCIS have mastectomies, some because they don't want to deal with anxiety about a possible life-threatening cancer.

Rakovitch wants to see the day when women could be tested for one or more "biomarkers" that would measure their actual level of risk.

"Then we could treat women at highest risk with more aggressive therapies, while avoiding over-treatment and needless side-effects for the majority of women who will never develop invasive cancer," she says.

To this end, Rakovitch is embarking on a research project in partnership with John Bartlett, program director of transformative pathology at the Ontario Institute for Cancer Research.

With support from the Canadian Cancer Society Research Initiative, Rakovitch has compiled a database of 5,500 women in Ontario diagnosed with DCIS between 1994 and 2003. Information on how the patients were treated and whether they later developed invasive cancer will be matched with molecular analysis of their tissue samples.

Dr. John Bartlett, Ontario Institute for Cancer Research


"We've never had access to this level of information on such a large scale," says Bartlett. "The goal is to map the molecular changes in the disease when it first presents, as well as the biology of an invasive recurrence, and to learn how to diagnose who is at risk of recurrence.

"We are looking over the top of the microscope into the eyes of the patient," he says. "It's very distressing for people going through a cancer diagnosis. We have a chance to develop a tool that will provide more certainty for patients and support more targeted treatment approaches."

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