report of BCRF scientific conference 2003

The first involves blocking the development of new blood vessels that feed tumor growth; the second focuses on the genetic profiling of breast tumors as a means of predicting patients' responses to chemotherapy drugs or their risk of cancer recurrence. Both have the potential to dramatically change the way breast cancer is treated.

This year's Conference was underwritten again by a generous gift from BCRF Advisory Board member Muriel Siebert, whose support last year funded the inaugural Scientific Conference--a meeting that was heralded as a great success. The Conference, held in conjunction with the Foundation's annual Luncheon and Symposium, was again hosted by Memorial Sloan-Kettering Cancer Center in Manhattan. The nearly 80 researchers who attended hailed from all reaches of the continental United States and from Great Britain, Israel, and Spain.

"Important advances in breast cancer come from creative thinking," said BCRF Medical Advisory Board Chairman and breast cancer oncologist Larry Norton, MD, who moderated the half-day Conference. "Yet, creative research does not typically receive funding from traditional sources. BCRF is willing to fund creative, innovative science, and that makes all the difference in the fight against breast cancer."

The Conference gives the investigators an opportunity to hear about the latest advances in the field of breast cancer research and enables them to share ideas and develop new collaborations. This year, six research projects-all funded by BCRF grants-were highlighted at the Conference, and investigators leading those projects presented updates of their research to their colleagues. BCRF researchers who attended the half-day Conference joined in the vigorous discussions following each presentation.

In recent years, cancer researchers have focused their efforts on blocking the development of new blood vessels that supply oxygen and nutrients to tumors, called angiogenesis, with the goal of preventing the lethal spread of cancer to other parts of the body. Judah Folkman, MD, of Children's Hospital and Harvard Medical School in Boston, a pioneer in the field of angiogenesis research, is now charting a new course of investigation funded with support from BCRF, he told his colleagues. He is investigating a way to prevent cancer by permanently disabling a "switch" inside tumors that, when turned on, induces tumors to recruit their own supply of blood vessels. One clue to turning off the switch may come from tumors themselves: He has recently found that only some tumor cells have the potential to become angiogenic, rather than all of them, as investigators previously thought. He now hopes to learn why certain cells do not have the capability of initiating angiogenesis.

Robert Benezra, PhD, of Memorial Sloan-Kettering Cancer Center, is also exploring novel ways of inhibiting angiogenesis, with the goal of preventing tumor growth and spread to distant organs. Specifically, his research has focused on two proteins-Id1 and Id3-that exist in blood vessels that nourish tumor growth but not in normal blood vessels. In laboratory models that lack Id, he has found that cancer still occurs, but it develops as cysts, which can be easily treated. These cystic tumors also lack oxygen, which indicates that blocking Id may be one way to prevent angiogenesis. His studies suggest that genes that are turned on by Id may be targets for the development of new angiogenesis inhibitors.

George Sledge, MD, of Indiana University, told his colleagues about new and ongoing clinical trials involving angiogenesis inhibitiors. In particular is a pivotal phase III clinical trial funded by BCRF that is evaluating whether the anti-angiogenesis drug bevacizumab combined with paclitaxel is more effective than paclitaxel alone in treating metastatic breast cancer in 685 women whose tumors have recurred following initial treatment. Other promising anti-angiogenesis inhibitors block a substance known as vascular endothelial growth factor, which is central to establishing a blood supply to tumors. Dr. Sledge noted that researchers are also working to better understand the side effects of these drugs, including hypertension and drug resistance. Another exciting avenue of research featured during the Conference-the use of sophisticated, new technology to profile patterns of gene activity in breast tumor cells-generated intense discussion about its potential to predict whether patients with breast cancer are likely to be cured by particular chemotherapy regimens or whether they are likely to experience cancer recurrence.

Jenny Chang, MD, of the Baylor College of Medicine in Houston, analyzed more than 12,000 genes in breast tumor samples and found that the activity of 92 of them could be used to predict patients' response to treatment with the drugs Taxotere and Herceptin. While her studies need to be validated in large groups of patients, this type of molecular profiling could help doctors select the best chemotherapy for a particular patient. It could also help to reduce patients' exposure to the toxic side effects of therapies in which they are not likely to benefit.

Lajos Pusztai, MD, D Phil, of the M.D. Anderson Cancer Center, also in Houston, told scientists about his work to identify a gene expression profile in breast tumors that is associated with a complete response to preoperative chemotherapy with paclitaxel and a combination of the drugs 5-FU, doxorubicin and cyclophosphamide (also known as FAC). This project was developed through a collaboration with Gabriel Hortobagyi, MD, also of M.D. Anderson Cancer Center. The investigators are now initiating a clinical trial to validate the use of these predictive markers among women with breast cancer. If the trial can establish the value of genetic profiling, the investigators expect to be able to identify patients who will benefit from preoperative chemotherapy with paclitaxel and FAC.

J. Dirk Iglehart, MD, of Brigham and Women's Hospital in Boston, reminded attendees that breast cancer is a diversified disease made of up many different types of tumors. To illustrate his point, he told of his recent discovery of a group of breast cancers that seem vastly different from other, more common breast tumor types. These so-called basal-like tumors are estrogen-insensitive and do not express the HER-2 protein, and they appear to accumulate more genetic damage than other breast tumors. He and his colleagues are now using gene expression profiling to determine whether it is possible to predict whether this genetically unstable type of cancer is susceptible to particular chemotherapy drugs.

"Today's presentations are a reminder of how far breast cancer research has come over the past decade," Dr. Norton told attendees, in recognition of The Foundation's 10th Anniversary. "Translational research-bridging the gap between the laboratory and the clinic-is really at the heart of what we're doing. We have a lot to celebrate."