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2013/2014 Annual Breast Cancer Research Grant Recipients

Dr. Chris Nelson, University of Victoria, Victoria

Project Title

Genome maintenance by FKBP prolyl-isomerases

Project Overview

Damage to DNA happens constantly from both intracellular & environmental factors. Fortunately, several sophisticated DNA repair machines are present to recognize & repair changes to DNA sequence.  When these machines fail, errors in our genes accumulate & this leads to cancer.

The malfunction of two key DNA repair machines, BRCA1 & BRCA2 is causal of hereditary forms of breast cancer. These two proteins are central to many aspects of DNA repair, but how they deal with different forms of damage under distinct conditions is not clear.

This lab is interested in a class enzymes called FKBP proteins because they have found that they work with BRCA proteins to ensure that the genomes escape mutation.  The data shows that, like BRCAs, FKBPs are needed to coordinate cell growth, and to survive at least one form of DNA damage. This project will resolve exactly how FKBPs, BRCA1/2 & a third breast cancer associated growth factor work in a coordinated fashion. This is important because cancers that have lost BRCA function are effectively treated with drugs that target secondary DNA repair processes. In these synergy-based chemotherapy strategies, we can drive cancer to a cellular suicide because BRCA-less cancer cells accumulate a lethal number of mutations before BRCA-containing normal cells. FKBPs are attractive cancer targets for a similar combination therapy, especially as FKBP-inhibitors already are in use. For these reasons, it is important to understand how BRCA proteins cooperate with FKBP proteins in DNA repair.

Dr. John Spinelli, BC Cancer Agency, Vancouver

John Spinelli.jpgProject Title

Occupational and other risk factors in relation to breast cancer subtype

Project Overview

We can treat breast cancer without knowing what causes it, but we cannot stop it.  Factors known to be associated with risk of developing breast cancer, such as shift work, are only markers and their biological connections to cancer remain unknown.  This study will examine the risk associated with shift work, exposure to polycyclic aromatic hydrocarbons, and other reproductive, lifestyle, genetic susceptibility and occupational factors in relation to breast cancer subtype.  Subtypes are based on important biological differences in tumour tissue.  If the risk associated with a given factor varies by biological subtype, two important benefits result:  1) information is gained about the biological link between the risk factor and causation of disease, and 2) better use of existing risk factor information is possible to predict occurrence of potentially more aggressive subtypes, and focus our prevention efforts on those at highest risk.
A recently completed breast cancer case-control study in British Columbia and Ontario has already generated important information on the risk factors for breast cancer including shift work, exposure to polycyclic aromatic hydrocarbons, physical activity and genetic susceptibility. This extension to the study will enable us to more fully characterize these risks by breast cancer subtype.

Dr. Ivan Nabi, University of British Columbia, Vancouver

Ivan Nabi.jpgProject Title

Autocrine motility factor & the Gp78 ubiquitin ligase: Role in cancer progression

Project Overview

Select breast cancers and certain other cancers are more difficult to treat, resulting in devastating diagnoses. Autocrine motility factor (AMF) & its receptor, Gp78, promote tumor cell motility and metastasis, and are linked to malignancy in various cancers. Gp78 is found both at the cell surface, where it internalizes AMF from outside the cell, and also inside the cell, where it targets proteins for degradation. This study hypothesizes that AMF and Gp78 act at the level of these cellular components to promote the survival of tumor cells leading to tumor progression & malignancy.

This study will also determine the relationship between AMF interaction with Gp78 and HER2 (a cell surface receptor), and breast cancer development. It will also develop new therapeutics that might both inhibit AMF regulation of Gp78 & its ability to cleave HER2. The researchers are optimistic these studies will lead to new therapeutics to treat these potentially terminal cancers and thus, provide a more hopeful prognosis for these cancer patients.

Dr. Alan Nichol, BC Cancer Agency, Vancouver

Alan Nichol.jpgProject Title

Provincial changes in adjuvant therapy use & compliance after lumpectomy in elderly women with early stage breast cancer

Project Overview

As the life expectancy of Canadians increases, it is important to determine the optimal treatment for elderly women.  In 2004, a randomized trial found that for certain women, radiotherapy after surgery may be safely avoided if they were regularly on hormonal therapy.  This has changed guidelines regarding radiotherapy for this group of women.  However, this study did not report on significant variables, or if women took the hormonal therapy regularly.
The purpose of this study is to look at elderly women with early stage breast cancer to determine how the use of radiotherapy and hormonal therapy has changed with time and how outcomes have changed.
This project will aid the review of BCCA’s provincial breast cancer guidelines to ensure that the treatment of elderly women in BC is appropriate and supported by its own data.  This study will also complement information from clinical trials, so that oncologists can fully discuss the adjuvant treatment options for this important and growing group of women.

Dr. Christine Wilson, BC Cancer Agency, Vancouver

Christine Wilson.jpgProject Title

Do General Practitioner letters improve screening mammography participation rates?

Project Overview

Screening mammography in BC is below the national target rate. Currently, 43% of women aged 50-69 years who had a normal initial mammogram do not return by 30 months.

A primary care physician letter has been developed using data from focus groups in BC that encourages women to participate in screening mammography again. This letter will be tested to see if it is more effective than the current Screening Mammography Program of BC (SMPBC) reminder letter.

The SMPBC database tracks the length of time from a woman’s last mammogram.  Overdue women have been identified from this database.  Their family physicians have been approached to participate in the study.  The goal is to determine if the screening mammography rate improves when women receive a letter from their primary care physician compared to the SMPBC.  There will also be other analyses to see if there are specific groups of women who are more likely to respond to the primary care physician letter.

The results of the study will benefit the SMPBC, so it can optimally use its resources. The study results will be presented & published to advance scientific knowledge about screening participation.  If this is a positive study, this may change how SMPBC implements its reminder system, and influence how other provinces approach their screening mammography reminder systems.

Dr. Caroline Lohrisch, BC Cancer Agency, Vancouver

Caroline Lohrisch.jpgProject Title

Comparison of trial reported benefits for adjuvant chemotherapy to outcomes in a general population for the same therapy

Project Overview

Creating a future without breast cancer requires not only that relevant research is conducted, but that the results of such research can be applied to the general breast cancer population in a clinically meaningful manner. In discussing the benefits of a particular chemotherapy with newly diagnosed breast cancer patients, Oncologists frequently refer to data from large clinical trials. However, treatments that have demonstrated a compelling advantage in the context of a carefully conducted trial may not offer the same magnitude of benefit in a ‘real-world’ setting.  Whether clinical trial results can accurately be extrapolated to the general population in routine clinical practice has not been well studied.
This research project is being conducted at the BC Cancer Agency and will draw upon data collected by the Breast Cancer Outcomes Unit and data provided by the National Cancer Institute of Canada Clinical Trials Group.  The study will compare breast cancer outcomes for women who received chemotherapy as part of a large clinical trial, with the outcomes experienced by a similar group of women treated at BC Cancer Agency centres who received exactly the same chemotherapy during the same timeframe.
Determining whether the benefits of a particular chemotherapy regimen persist under conditions reflective of usual care will assist Oncologists in choosing the right treatment, for the right woman, for the right disease.