report of BCRF symposium 2006

Knowing your enemy is an important strategy in winning any battle. The breast cancer fight is no different. An elite set of cells called breast cancer stem cells are beginning to yield their biological secrets - secrets that may lead to cures.

At BCRF's 2006 Symposium, the Foundation's scientific director Larry Norton, MD, introduced a panel of BCRF-supported scientists who lead efforts to define and understand breast cancer stem cells.

"When I use the term 'breast cancer stem cell' I mean the cell that is driving the tumor, and has gained the capacity for self-renewal through mutations that led to the cancer. These are the cells that must be eliminated if we wish to cure more women with breast cancer," said one of the panelists, Michael Clarke, MD, a scientist based at Stanford University. Clarke, along with four other top researchers including Joan Brugge, PhD, of Harvard Medical School; Jenny Chang, MD, of Baylor College of Medicine; Marc Lippman, MD, of the University of Michigan, and Geoffrey Wahl, PhD, of The Salk Institute of Medicine, helped clarify the differences between the beneficial stem cells present in the body from conception through adulthood, and the tumor-driving, self-renewing cells that are more stealthy than the majority of cells that make up breast cancer tumors.

Though scientists and physicians-many funded by The Breast Cancer Research Foundation-have made great progress in the past 20 years turning breast cancer into a survivable disease, some cancers remain intractable. Recurrence is still a threat for many survivors. The crux of the problem may be breast cancer stem cells, their existence and role in cancer and what must be done to get them to stop fueling breast cancer.

As Jenny Chang pointed out, the breast cancer field may need conventional therapies plus new ones that attack breast cancer stem cells in order to achieve a cure. Breast cancer stem cells have demonstrated their ability to resist established therapies. Chang recently initiated a clinical trial in Houston that tests the drug lapatinib as a therapy for small residual cancers in women treated for locally advanced breast cancer, with encouraging results. Lapatinib or other drugs may be able to subdue breast cancer stem cells beyond the scope of conventional chemotherapies.

Dr. Norton emphasized the fact that while breast cancer stem cells pose a problem in curing the disease, a possible benefit is that they may be the same across all or many breast cancers. Therefore, studying their basic characteristics, as Joan Brugge and Michael Clarke do, brings a potentially large payoff.

Clarke described his efforts in learning the differences between normal stem cells in the breast and the breast cancer stem cells that form via genetic mutations and aberrations in cell division. He described how the ductal system in the breast is regulated by stem cells. Clarke's foundational studies not only verify the existence of cancer stem cells, but also shed light on their hidden weaknesses--weaknesses that could be exploited by drugs designed to specifically target them.

Brugge's research focuses on understanding how oncogenes, the originating genes that drive cancer growth, control their cellular environment by avoiding death processes that eliminate abnormally proliferating cells. Her studies are critically important and expand the value of basic findings that Clarke and others are bringing to the field. Brugge has discovered that some breast cancer cells not only avoid a natural cell-clearing process called apoptosis, or programmed death, they also escape a secondary cell-clearing process called autophagy. Autophagy is triggered by metabolic deficiencies in cells that are not growing in their normal place in the architecture of the breast's duct-like glands. Scientists will be better able to target breast cancer stem cells by understanding more about how they avoid cell death.

Geoffrey Wahl takes a slightly different approach to breast cancer stem cells. A cell biologist interested in basic mechanisms of molecular biology, Wahl traces what happens from the time that breast stem cells are first established-in an embryonic stage-all the way to adult mammary tissue. Mapping out the normal breast tissue cells including stem cells from embryo to adulthood will provide a crucial natural history to the development of breast cancer stem cells and help reveal when and under what conditions the harmful cells arise.

Questions from the morning Symposium's large audience, composed predominantly of non-scientists who support breast cancer research at the Foundation's annual Awards Luncheon, spanned important topics. Among those questions were several about a type of breast cancer seen in growing numbers of women under and around age 30. Called "triple negative" breast cancer, the name means only that this is a disease that does not correspond to any one of the three known hormone receptors: ER (estrogen receptor), PR (progesterone receptor) and HER2 (human epidermal growth factor receptor).

Panelist Marc Lippman studies the role of hormones in breast cancer, specifically homing in on genes that correlate with ER-associated disease. "We still don't know exactly how hormones work in breast cancer," he says. With a better understanding of the genetics behind ER-positive disease, Lippman is helping identify which patients will respond to the various endocrine therapies (also known as hormone therapies) developed in the past 10 years. Lippman's research is important because it may also help to unravel why women with non-hormone receptor cancers, like triple-negative, have poorer outcomes than those with any of the known hormone-positive diseases.

Jill Rose Award Presented to Dr. Larry Norton for New Web Portal
In a gesture typical of Dr. Larry Norton's community-minded spirit, he accepted the Jill Rose Award on behalf of the entire Medical Advisory Board and donated the cash prize associated with the Award to the Foundation for the establishment of a new, dedicated website only accessible to BCRF grantees. The site, to be launched later in the year, provides a permanent networking mechanism for BCRF researchers. The project adds an exciting new layer to the opportunities for shared data and research collaborations already built in to the Foundation's annual events.

Norton described its value: "The research field can be compared to building an automobile--one person specializes in tires, another in brakes, another in steering--but unless those specialists get together and talk and compare what they know, they're never going to build a working automobile. We are going to create an electronic environment that will connect BCRF grantees in ways that will advance the whole field, that will build bridges and create more opportunities for finding cures."