report of BCRF symposium 2008

The headline for this year's BCRF public symposium and luncheon on October 29, "Not all cancer cells are alike" can be taken in two ways. In the scientific sense, breast cancer is being parsed into more and more subcategories, in some cases revealing hidden abilities of cancers that can lead to recurrence. In another sense, the odds for surviving breast cancer have improved dramatically in the past fifteen years. The chances for survival are better for breast cancer than for other common cancers such as lung or ovarian cancer. Part of this improvement can be attributed to the dedication and success of the outstanding researchers funded by The Breast Cancer Research Foundation.

"Every year, it gets better," said Evelyn Lauder, Founder and Chairman of BCRF, following a standing ovation at the beginning of the luncheon. "Can you believe that 166 scientists will receive grants of nearly $35 million this year?" Myra Biblowit, President of BCRF, cited some of the most significant accomplishments made by BCRF-funded researchers over the organization's fifteen-year history. Among these are a public atlas of all the known genes associated with breast cancer, refinement of treatments based on a woman's individual genetics, the creation of an entirely new "science of survival," and an understanding of which dietary factors count most heavily toward developing breast cancer. Biblowit also described three key ingredients that have made BCRF's philanthropy so successful for fifteen years--"the caliber of the scientists invited to submit proposals, the freedom to pursue research that they feel will lead directly to cures and better prevention, and the belief in world-wide collaboration because the stakes are too high to do otherwise."

The public symposium preceding the luncheon provided a glimpse at how this elegant model for accomplishment works. A panel of six BCRF experts gathered to discuss an important and emerging aspect of breast cancer. While it is widely understood that breast cancer is a collection of diseases, more recently scientists have identified a new class of cells within tumors that challenges our understanding of breast cancer. A specialized sub-population of cells--a small minority of the total number of tumor cells--have the distinct ability to initiate new tumors. While the consensus on what to call these cells and how to explain their existence is still evolving, many scientists refer to the tumor-initiating cells as cancer stem cells. Moderated by the BCRF's Scientific Director, Larry Norton, MD, of Memorial Sloan-Kettering Cancer Center, presenters Joan S. Brugge, PhD, of Harvard Medical School, Michael F. Clarke, MD, of Stanford University, Charlotte Kuperwasser, PhD, of Tufts University School of Medicine, Hope S. Rugo, MD, of the University of California at San Francisco and Robert A. Weinberg, PhD, of the Whitehead Institute, elaborated on what we know about tumor-initiating cells.

Weinberg led the presentations, explaining to the packed conference room at the Waldorf=Astoria that adult stem cells--normal cells that exist throughout our bodiesâ€"assist in the body's self-renewal process by initiating new tissues as old cells die off. He went on to explain that the same is true for tumors; a small minority of cells represents the heart of a tumor's ability to thrive. What's more, this relatively recent knowledge explains why a small proportion of tumor cells may be resistant to the treatments aimed at their fast-growing sister cells. Cancer stem cells may be the source of a tumor's recurrence after breast cancer has by all indications been eradicated from the body.

Kuperwasser, who trained under Weinberg and is an expert in normal breast development and breast cancer biology, added to the description of tumor-initiating cells. She cited research that suggests that stem cells can break away from the primary tumor, circulate to other areas of the body and find a protective niche where they can reside indefinitely. Kuperwasser and others are learning more about the conditions that keep tumor-initiating cells dormant versus active. This may help explain why breast cancer can recur over a long horizon, as much as 10-20 years after treatment.

Next, Michael Clarke, a researcher who led the discovery of breast cancer stem cells in 2003, explained that breast cancer-initiating cells live by a different set of rules than other cancer cells. He and several other BCRF researchers study the mechanisms that set cancer stem cells apart. Learning what makes them tick may help scientists develop treatments targeted to these cancer cells, too.

Hope Rugo, a clinician-researcher, discussed the possibilities of patient-related factors that aid tumor-initiating cells, and how an understanding of those factors could be part of future treatments.

Joan Brugge described her pioneering research in creating three-dimensional biological structures resembling the glands of the breast. These structures permit Brugge and her colleagues to learn new ways to block the abnormal behavior of cells, including cancer cells and cancer stem cells.

The panelists--representing an outstanding range of laboratory, translational and clinically-grounded research on a vexing aspect of breast cancer--demonstrated how the creation of new knowledge leading to new ways to anticipate and treat the disease comes about through careful consideration and collaboration.

As is true every year, symposium attendees filling the conference hall had informed questions on a range of topics including cancer stem cells, prevention and nutrition, targeted therapies and the duration of treatments. Norton reminded participants when they queried panelists and their colleagues about nutritional supplements that "cancer cells are your cells--they are not foreign and they live off of the same things your normal cells live off of." A revealing discussion about the current standards for vitamin D and folic acid supplementation took place. "We do know for sure that consistent exercise and minimum weight gain are important prevention measures that everyone can try to achieve," said BCRF grantee Marc Lippman of the University of Miami.

The 2009 Jill Rose Award went to Robert Weinberg. Larry Norton introduced Weinberg as "one of my scientific heroes even before he became Discover magazine's Man of the Year in 1982." Weinberg, who modestly told luncheon attendees that he feels lucky to go to work every day in an environment where his "curiosity-driven research" is appreciated and supported, has made numerous discoveries that anchor cancer research throughout the world. In 1982, he discovered the first human cancer-causing gene, the ras oncogene. His laboratory also discovered a second type of cancer-causing gene, called a tumor suppressor gene. It normally brakes rapid cell growth and is lost from many cancer cells. More recently, his group has found that primary cancers can stimulate the growth of metastases by sending signals to the bone marrow. He believes that this may offer an opportunity to combat metastases by interrupting these blood-borne signals. He expressed gratitude to BCRF for essential financial support which enabled his laboratory to begin a new focus on breast cancer five years ago.

The annual scientific retreat on October 28 followed a new format that emerged from suggestions from the entire group. Instead of gathering all grantees to share and discuss ideas related to one theme presented by a small group of speakers, as it has done in past years, this year's format was designed with more of a "think tank" atmosphere in mind. All researchers actively participated in six simultaneous sessions that had earlier been proposed and agreed upon by consensus: Biomarkers; Cancer Stem Cells and Cancer/Stroma Interactions; Therapeutic Targets/Targeted Therapeutics; Inherited Susceptibility Genes; Molecular Classification, Prognostication and Prediction; and Prevention and Survivorship. When he welcomed the entire group at the outset, Larry Norton encouraged the researchers to use the sub-groups the way jazz musicians would use a jam session--to open up creativity and improvisational thinking. That advice proved to be effective. During the summary hour for which the entire group reconvened, session moderators summarized their discussions, all of which had come up with new collaborative projects or ideas to advance breast cancer research from those topical perspectives.