Dr. Rama Khokha, a Senior Scientist at Princess Margaret Cancer Centre, will lead molecular breast cancer prevention research in a project funded by Breast Cancer Canada. (Photo: UHN)

Breast Cancer Canada has announced $3 million in funding to support molecular breast cancer prevention research at the Princess Margaret Cancer Centre.

The announcement, made on June 3 during the American Society of Clinical Oncology (ASCO)'s Annual Meeting, is three-year funding focused on defining targeted prevention strategies in breast cancer, starting with women at high risk.

The work will be led by Dr. Rama Khokha, Senior Scientist at the Princess Margaret.

"With increased screening efforts over the last few decades, breast cancer is being caught at earlier stages," Dr. Khokha says. "High-risk individuals, often young women with a family history and genetic predisposition, can be identified before symptoms show up.

"However, there are very few preventative options that we can offer these young women – and these options are often very drastic and invasive, such as mastectomy. There is an unmet need to develop more precise prevention strategies that are catered to the varying degrees of breast cancer risk.

"This funding and our momentum will allow us to exploit windows of opportunity to intervene early."

Dr. Khokha's team studies abnormal stem cells that drive breast cancer development. The growth trajectory of these precursor cells has gone awry and they induce molecular and structural changes in the breast.

Dr. Khokha's program searches for the root cause of these changes in order to develop molecularly targeted therapies. In the past few years, she has spearheaded efforts in cancer prevention at multiple levels.

At the Princess Margaret, she has united basic and clinical research teams with the shared goal of precision molecular prevention.

Nationally, Dr. Khokha received funding from the Terry Fox Research Institute and CIHR/ICR to support an interdisciplinary program on early interception of breast cancer; and has engaged the parliamentary health caucus leadership at Research Canada's "Cancer Gone" session.

Internationally, she led the Princess Margaret in becoming the first Canadian member of the Northwestern Cancer Prevention Consortium (NCPC) in the United States, which conducts clinical trials in prevention.

In recognition of Dr. Khokha's outstanding work and research focus, Breast Cancer Canada granted $3 million to support her team's preventative breast cancer research.

"The best way to stop breast cancer is to stop it from occurring, and today Breast Cancer Canada is making an investment in prevention," says Kimberly Carson, CEO of Breast Cancer Canada. "Breast cancer research has made remarkable progress, but we still have work to do."

Dr. Rama Khokha, front, second from right, and her research group at the Princess Margaret Cancer Centre. (Photo: UHN)

With the new funding, Dr. Khokha and her lab can increase their capacity to continue building on and leveraging resources they have already developed. She categorizes her team's research effort into three pillars: discover, dissect and target.

To discover and understand the heterogeneity in breast cancer and provide insights into precision care, her team analyzes high-risk breast tissue from consented patients undergoing risk-reducing surgeries at the Princess Margaret.  

The funding will help expand the size and diversity of the breast tissues they can collect and analyze. This includes the creation of a unique High-risk Breast Cancer Registry (Hi-CaRe) with clinical follow-up data on more than 3,000 patients at UHN in collaboration with the cancer centre's high-risk breast screening program.

Once the study samples are in place, the team will thoroughly study the breast tissues at the molecular level through multimodal analysis and mapping. This deep molecular analysis includes methylation analysis, proteomics, metabolomics, and in profiling matched liquid biopsy samples. This will allow the team to dissect the distinctions between high-risk groups.

Lastly, utilizing an established pipeline from their cell and molecular analyses, they identify potential targets and drugs for preventing breast cancer. The team uses two approaches for this purpose: a "Discovery to Interception" pipeline and a "Cancer Precursor Detection" pipeline.

In Discovery to Interception, the team sets up a drug screening process where potential molecules go through various assays to assess their effectiveness. The Cancer Precursor Detection pipeline focuses on the non-invasive detection of early onset of breast cancer through liquid biopsies.

"I'm elated and excited that Breast Cancer Canada believes in our program," Dr. Khokha says. "This funding will make it easier and faster for us to make progress."

Dr. Khokha's team also collaborates with Shelley Westergard, nurse navigator and clinical coordinator of the high-risk breast screening program at the Princess Margaret, Dr. Hal Berman, a clinical pathologist at Toronto General Hospital, and Dr. Thomas Kislinger, Senior Scientist at the cancer centre.

"Mrs. Westergard was pivotal in setting the foundation for the cancer registry, and this program would not be possible without Dr. Berman who has guided breast tissue collection and Dr. Kislinger's clinical proteomics program," says Dr. Khokha.

"We are excited and grateful to Breast Canada Cancer for this funding," says Dr. Brad Wouters, Executive Vice President, Science and Research at UHN. "Dr. Khokha is a tremendous scientist and leads a very talented team.

"This grant will help her lab to advance our understanding of breast cancer and gain insight into new strategies for disease prevention."​​

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