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Timothy Whelan/Irene Andrulis
McMaster University, Hamilton, ON
Discovery and use of Clinically Relevant Molecular
Changes in Breast Cancer
Over the past decade, researchers have made major steps toward
understanding what happens on the molecular level when a cell becomes
cancerous. Despite these advances,
however, there have been few changes in breast cancer treatment. The goal of
these investigators is to speed up the discovery of new molecular changes and
the application of these discoveries to the treatment of women with breast
cancer. This group of scientists will
study the importance of genetic changes in breast cancer and will translate
these results more directly into patient care. They will begin by focussing on a gene called HER-2, which is
known to play a role in breast cancer, and will then identify other important
molecules and how they can be used to benefit breast cancer patients.
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Core Component Funding
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Component Research Projects
William Muller and Morag Park
McMaster University, Hamilton, ON
When
breast cancer is fatal, it is usually because it has spread to other parts of
the body. Although several genes
appear to be involved in this process, how they cause breast cancers to
spread is still not well understood.
Drs. Muller and Park are studying two genes called HER-2 and Met to
find out whether they stimulate the spread of breast cancer cells to other
body parts. They will do this by
measuring the activity of these genes in laboratory-grown breast cells,
breast cancer cells from patients, and genetically altered mice. Their results may lead to new approaches
to the treatment of breast cancer that has spread.
Vincent Gigučre
Royal Victoria Hospital, Montreal, PQ
Estrogen, which is known
to play a role in breast cancer development, acts on cells by attaching to a
molecule called the estrogen receptor.
This molecule is involved in the growth, division and specialization
of normal breast cells. Dr. Giguere's team is studying the interaction
between the HER-2 gene and the estrogen receptor. They will create genetically altered mice in order to determine
how estrogen receptors work in both normal and cancerous breast cells. Their
results will increase our knowledge of the interactions between hormones and
other molecules in breast cells, which may suggest new strategies for breast
cancer prevention and treatment.
James Woodgett
Ontario Cancer Institute, Toronto, ON
Breast cancer begins,
grows and develops when various genes are altered within the cells. Although these genes interact and affect
one another, most research has focussed on the effects of a single gene at a time.
Dr. Woodgett's team is using screening chips printed with thousands of genes
to more efficiently and effectively identify those genes that are altered in
breast cancers and how they interact and influence each other. They will then use genetically altered
mice and data from breast cancer patients to confirm the roles of these genes
in breast cancer development. They
hope that by identifying the early genetic changes that occur in breast
cancer, they will discover ways to block these changes and stop breast
cancers from developing.
Frances O'Malley
Mount Sinai Hospital, Toronto, ON
A new drug called Herceptin is useful for the
treatment of women whose breast cancer cells contain alterations in the HER-2
gene. However, the current technique used to determine which women have these
genetic changes appears to be somewhat inaccurate, since it also identifies
as positive some women who do not have these changes and will probably not
benefit from Herceptin treatment. Dr.
O'Malley's team is testing a new method to identify patients who are positive
for HER-2 changes. They plan to
determine whether this new test is more accurate in identifying women whose
tumours have these alterations in the HER 2 gene, and whether it will better
predict which patients will respond to Herceptin. Such a test would allow Herceptin to be more effectively used
in breast cancer patients.
Kathleen Pritchard
Toronto-Sunnybrook Regional Cancer Centre, Toronto, ON
Predictive factors are
traits of a cancer that predict how the affected patient will respond to a
certain treatment. It has been
suggested that the activity level of the HER-2 gene in breast cancer cells is
a predictive factor: women with overactive HER-2 genes may not respond to
certain therapies. Dr. Pritchard's team is testing the theory that
overactivity of the HER-2 gene predicts a lack of response to one hormone
drug, but not to either of two others.
They will measure the gene's activity level in tissues from more than
900 women participating in trials of three different hormonal agents,
tamoxifen, arimidex and faslodex, and will correlate this with the trial
results. If the theory is proven
correct, the activity level of HER-2 could be used to help doctors better choose
individual hormone therapy for each breast cancer patient.
Timothy Whelan
McMaster University, Hamilton, ON
A new drug called Herceptin has been studied in a
number of trials involving women with breast cancer that has spread outside
the breast. It appears that this drug
is effective in women whose cancer cells contain changes in the HER-2 gene.
However, it is not known how useful the drug will be in practice. Dr.
Whelan's team plans to examine the results when Herceptin is introduced in
Ontario, British Columbia and Quebec, three provinces with different ways of
delivering cancer care. They will
collect data about the patients receiving Herceptin, as well as other breast
cancer patients, and conduct focus groups and surveys to learn patient and doctor
opinions. Their results will show what
kinds of factors affect how often a new drug is used and whether all
appropriate patients have access to it.
This will allow more effective use of other anticancer drugs in the
future.
Michael Pollak
Lady Davis Institute, Montreal, PQ
Insulin-Like Growth Factors and Breast
Cancer: A Canadian Research Network
Many useful ways to prevent and treat breast cancer involve
hormones. This multidisciplinary
group of researchers is studying a family of hormones called insulin-like
growth factors, which help to control cell division in both breast cancer
cells and normal breast cells. High
levels of these hormones also appear to be associated with an increased risk
of breast cancer. The group will do
various kinds of lab studies and patient studies in order to better
understand how insulin-like growth factors work, how they are related to
breast cancer, and how their activity might be altered. Their results may suggest new ways to
treat or prevent breast cancer.
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Core Component Funding
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Component Research Projects
Jacques Brisson
CHA-Pavillon St-Sacrement, Quebec, PQ
An insulin-like growth factor called IGF-1, and
the protein that carries it in the bloodstream (called IGFBP-3), affect the
growth of breast cells. In addition, levels of these molecules are known to
be related to the risk of breast cancer.
The presence of dense areas of tissue in a woman's breasts is also
associated with a higher risk of breast cancer. Dr. Brisson's group is trying
to determine whether levels of IGF-1 and IGFBP-3 are directly related to the
presence of dense breast tissue.
Their results will show whether or not these molecules play a role in
the development of breast cancer and will help to clarify whether the
presence of dense tissue could be used to show how well cancer prevention
strategies are working.
Cheri Deal
Hôpital Sainte-Justine, Montreal, PQ
An insulin-like growth factor called IGF-2 is
produced by breast cancer cells and appears to be involved in the growth and
development of these cancers. However, the level of IGF-2 in the blood does
not seem to correlate with the risk of breast cancer. Dr. Deal believes that
this might be because the amount of IGF-2 in the blood doesn't accurately
reflect the amount produced by breast cancer cells. Her team now plans to
test this theory. They will also determine which cells in normal breast
tissues and breast cancers are responsible for making IGF-2, and whether
IGF-2 activity levels are related to a cancer's stage of development. In
addition, they intend to find out how a certain change in the IGF-2 gene
occurs and whether it occurs more often in women with cancer. Their results
may lead to the development of tests for women at high risk of developing
breast cancer.
Joanne Emerman
University of British Columbia, Vancouver, BC
Breast cancer is often studied in cells called
human breast epithelial (HBE) cells, since these are the cells that give rise
to this cancer. However, cancer cells grown from HBE cells in the laboratory
are not exactly the same as the cancer cells found in patients. Dr. Emerman's
team has developed a way to grow HBE cells that are more like patient cells.
They now plan to study the interactions between HBE cells and two
insulin-like growth factors (IGFs) believed to be involved in breast cancer development.
They will determine the role of IGFs in normal HBE cells and how IGF activity
relates to breast cell growth. Their results will provide important
information about differences between normal breast cells and cancerous
cells.
Jorge Filmus
Sunnybrook & Womens College Health Sciences Centre, Toronto, ON
Insulin-like growth factors (IGFs)
stimulate the growth of breast cancer. A molecule called glypican-3 is known
to block the activity of IGFs and therefore could possibly stop breast
cancers from growing. Dr. Filmus has discovered that this molecule is less
active than usual in breast cancer cells. He now plans to further investigate
glypican-3 and its effects. If he can prove that glypican-3 stops breast
cancer growth, it may lead to the development of new breast cancer
treatments.
Steven Narod
University of Toronto, Toronto, ON
The amount of IGF-1 in a woman's blood is
related to her risk of developing breast cancer. IGF-1 levels vary widely
among women, but all the reasons for this variation are not known. Dr.
Narod's team will measure IGF-1 levels in 1,000 healthy women and try to
correlate these levels with various lifestyle factors (including diet,
smoking and hormone use) and alterations in any of eight genes. The team also
plans to determine the effects of dense breast tissue (a known breast cancer
risk) and IGF-1 levels in 300 women who have genetic changes that increase
their risk of breast cancer. Their results will help doctors to better
counsel women at high risk of breast cancer, and may suggest ways to prevent
breast cancer from developing.
Michael Pollak
Lady Davis Institute, Montreal, PQ
The levels of the various insulin-like growth
factors (IGFs) in a woman's blood appear to be related to her risk of
developing breast cancer. Dr. Pollak is measuring these levels in blood
samples from numerous women who are participating in breast cancer prevention
or treatment trials. He will then determine how IGF levels correlate with
both the risk of breast cancer and the likelihood of survival if it develops.
His results will increase our knowledge of the roles that IGFs play in breast
cancer, which may lead to new ways to prevent or treat this disease.
Peter Watson
University of Manitoba, Winnipeg, MB
Breast cancer develops when genes in breast cells
are altered. Some of the genes that may be altered are those that determine
how breast cells communicate. Changes in these genes are known to affect the
growth of advanced cancers, but it now appears that they might also affect
the early development of breast cancers. Insulin-like growth factors (IGFs)
appear to be involved in cell communication, and IGF-1 is associated with an
increased risk of breast cancer. Dr. Watson's team plans to determine whether
the effects of IGF-1 are changed or increased in the breast cells of women
with a high risk of developing breast cancer. Their results will increase our
understanding of IGF-1's role in breast cancer development and may lead to
better ways to predict which women are most at risk for this disease.
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Full Award
Core Award
2000-2001:
$273,728
2001-2002:
$261,342
2002-2003:
$368,601
2000-2001:
$139,583
2001-2002:
$145,405
2002-2003:
$192,939
2000-2001:
$132,424
2001-2002:
$132,424
2002-2003:
$132,424
2000-2001:
$222,972
2001-2002:
$222,972
2002-2003:
$271,098
2000-2001:
$112,847
2001-2002:
$112,847
2002-2003:
$120,847
2000-2001:
$135,786
2001-2002:
$117,913
2000-2001:
$196,791
2001-2002:
$193,121
2002-2003:
$193,121
Full Award
Core Award
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