Judy E. Garber, MD, MPH

2009-2010 BCRF Project:
(made possible by generous funding from Coach)

Dr. Garber continues to work in hereditary breast cancer and triple negative disease. Her laboratory's first neoadjuvant trial of platinum for women with triple negative breast cancer gave rise to a second trial that has completed accrual. Based on their results, they have begun the Phase I trial combining platinum and a promising new agent, a PARP inhibitor, that has shown exciting early results in women with BRCA1 and BRCA2 mutations and advanced ovarian and breast cancers. Once the doses are established, they will submit for IRB review a multi-center trial that they developed and lead comparing platinum to platinum plus the new PARP inhibitors, a class of drugs. Because of the success of the Parp Inhibitor in women with BRCA1/2 mutations and recurrent breast and ovarian cancers, the researchers are going to be allowed to expand their trial to make the drug more widely available to women awaiting the development of definitive trials. They are conducting this trial with a number of other BCRF investigators (Drs. Baselga, Carey, Tung/Schnitt, Richardson, Iglehart, Livingston, and Domchek).

They also continue to study the breast tumors from women in the platinum trials to search for new targets for therapy, and new markers with which to predict response to current treatments. They have been studying familial lobular breast cancer, and fortunately, have shown that only a small proportion - 2% approximately, have lobular breast cancer linked to mutations in the CDH1 gene. This is good news, and has implications for management. Their specimens again come from BCRF collaborators (Offit, Domchek, Brown, Ford, Olopade). The researchers are in the midst of their collection and analysis of progesterone receptor in the normal breast tissue of women with BRCA1 mutations as a target for preventive therapies. They are also actively collecting fixed and frozen tissue samples from women undergoing prophylactic mastectomies for their BRCA1 or BRCA2-associated breast cancer risk for their most recent study of ALDH1 stem cells as potential markers of breast cancer evolution in mutation carriers. Dr. Garbe''s laboratory collaborator, Dr. Silver, continues to investigate the role of BRCA1 in both DNA repair and differentiation

Triple negative breast cancers (TNBC) have been recognized as presenting particular challenges for breast cancer treatment. Validated molecular targets for therapeutic interventions are lacking for these tumors. Further, several lines of evidence suggest that not all TNBC are alike, but rather that there are likely to be several subtypes defined by histologic and/or molecular features. If they are different at the molecular level, the subtypes of TNBC may require different treatments as well. The Garber group has been studying the subset of TNBC that respond to the platinum agents, which work in part by cross-linking DNA and causing particular kinds of DNA damage that some tumor cells cannot repair, so they are effectively killed. Platinums may have more than one therapeutic effect, however, so it seems important to try to tell whether tumors that are sensitive to platinums are the same tumors that are sensitive to drugs used more often in breast cancer treatment, anthracyclines and taxanes, or are different. If they are the same tumors, then there is little advantage to continuing to work with platinum. If they are different, then there is important tumor biology that could form the basis for an assay that could ultimately guide therapy at breast cancer diagnosis, perhaps not only to platinums, when appropriate, but possibly to the new PARP inhibitor agents as well, since they also work through a DNA repair vulnerability. Since it is unlikely that the scientists would do a study comparing platinums to anthracyclines/taxanes directly at this time, this kind of inquiry from established datasets may be a more rapid way to advance the field.

Mid-Year Progress Report:
Dr. Garber and her team continue to work in hereditary breast cancer and triple negative disease. Their first neoadjuvant trial of platinum for women with triple negative breast cancer gave rise to a second trial that has completed accrual. Based on their exciting results, they have nearly completed the Phase I trial combining platinum and the Astra Zeneca PARP inhibitor, which will provide the safe dose of the PARP inhibitor for use in combination with cisplatinum in the randomized multi-center neoadjuvant trial that will begin, they hope, in spring, 2010. Because of the success of the Parp Inhibitor in women with BRCA1/2 mutations and recurrent breast and ovarian cancers, they are going to be allowed to expand the trial to make the drug more widely available to women awaiting the development of definitive trials. They are conducting this trial with a number of other BCRF investigators (Drs. Baselga, Carey, Tung/Schnitt, Richardson, Iglehart, Livingston and Szallasi).

They also continue to study the breast tumors from women in the platinum trials to search for new targets for therapy, and new markers with which to predict response to current treatments. They have been studying familial lobular breast cancer, and fortunately, have shown that only a small proportion - 2% approximately, have lobular breast cancer linked to mutations in the CDH1 gene. This is good news, and has implications for management. Their specimens again come from BCRF collaborators (Offit, Domchek, Brown, Ford, and Olopade). They continue to study progesterone receptor in the normal breast tissue of women with BRCA1 mutations as a target for preventive therapies. They are also actively collecting fixed and frozen tissue samples from women undergoing prophylactic mastectomies for their BRCA1 or BRCA2-associated breast cancer risk for their most recent study of ALDH1 stem cells as potential markers of breast cancer evolution in mutation carriers.

For Dr. Garber's most recent project, she and her team are evaluating a new tool, Molecular Inversion Profiling (MIP) as a potential measure of DNA damage in fixed tissue. With investigators at the Ohio Status University, they are assembling a collection of fixed tissue from women with triple negative breast cancers who were treated with neoadjuvant chemotherapy with established regimens, and will compare their MIP profiles to their tissues from women treated with platinum, to see whether the MIP will be a predictor of response to platinum only, or to chemotherapy in general, which would have important implications for future care.

Bio:
Dr. Garber is Director of the Cancer Risk and Prevention Program at the Gillette Center for Women's Cancers at Dana-Farber Cancer Institute. She is also an attending physician at Dana-Farber's Breast Evaluation Center, an associate physician at Brigham and Women's Hospital and an associate professor of Medicine at the Harvard Medical School. Dr. Garber's research is focused on genetic susceptibility to breast, ovarian and other cancers, and the development of novel medical strategies to prevent cancer. She uses the tools of cancer epidemiology and biostatistics, genetics and molecular biology to identify women at high risk for breast cancer.

Dr. Garber has been at Dana-Farber Cancer Institute since 1988 when she joined the faculty after completing a fellowship in Medical Oncology at DFCI and fellowships in Cancer Epidemiology and Biostatistics at the National Cancer Institute and DFCI.

A graduate of the University of Virginia, Dr. Garber earned her medical degree and her master's degree in public health from Yale University School of Medicine and completed her internship and residency at Brigham and Women's Hospital and the Brockton-West Roxbury Veteran's Administration Medical Center. In 2010, Dr. Garber was elected President-elect of the American Association of Cancer Research.