The Breast Cancer Research Foundation: What We've Accomplished
The Breast Cancer Research Foundation was established by Evelyn H. Lauder in 1993, with the intention of bringing about a cure for breast cancer in our lifetime. Larry Norton, MD, of Memorial Sloan-Kettering Cancer Center, has directed the Foundation's scientific activities since its beginnings. In 2002, BCRF expanded its mission to include prevention as well as cure, reflecting the direction of its research grants aimed at prevention as well as treatment. Since inception, BCRF has increased its annual funding level more than 200 times over, and in 2012-2013 will be supporting 197 dedicated researchers at major medical institutions across the globe--a very long way from the $159,000 to eight researchers awarded in 1994.
BCRF-funded research has helped save lives and significantly improved the quality of care and survivorship for tens of thousands of breast cancer patients in the past decade and a half. The research itself has revealed that "cure" is a mosaic made up of as many approaches to diagnosing, treating, preventing and surviving as there are different types of breast cancer.
The following areas of BCRF research accomplishment have laid the foundation for breast cancer prevention and cure:
Currently, 91 cents of every dollar spent by BCRF is directed towards breast cancer research and awareness programs.
BCRF is the lead organization in funding research on genetic susceptibility in breast cancer. Since 1997, The New York Breast Cancer Study, under the direction of Mary-Claire King, PhD, University of Washington, Seattle, and Joan Marks, MS, Sarah Lawrence College, Bronxville, NY, has been identifying the genes underlying inherited risk of breast cancer among women of Ashkenazi Jewish ancestry. Working in tandem since 2001, the Israeli Breast Cancer Study, under the direction of Ephrat Levy-Lahad, MD, Shaare Zedek Medical Center, Jerusalem, determines breast and ovarian cancer risk in the Ashkenazi population in Israel by identifying BRCA1 and BRCA2 carriers through healthy males. This program is a model for genetic breast cancer prevention screening in general. In addition, BCRF researchers have made the following contributions:
Breast Cancer Stem Cells
- 2002 The finding that breast cancer is a collection of diseases with different patterns of gene activity, which relate directly to determining prognoses and selecting most appropriate treatments. (Charles Perou, PhD, University of North Carolina, Chapel Hill, and many others from BCRF)
- 2006 The collection of more than 1300 human genes related to breast cancer, which is now available to scientists worldwide for studying breast cancer. (Joan Brugge, PhD, and Joshua LaBaer, MD, PhD, Harvard Medical School, Boston)
- 2008 New genetic risk markers for breast cancer discovered and sister study searching for new genetic protective markers for breast cancer is launched (Kenneth Offit, MD, MPH, Memorial Sloan-Kettering Cancer Center, New York)
Reports of the first clinical studies in breast cancer stem cells this year cited the important 2003 discovery of the fundamental properties of the cells that are the very roots of breast cancers--research conducted with BCRF funding (Michael Clarke, MD, Stanford University, Stanford, CA, Jenny Chang, MD, and Kent Osborne, MD, Baylor College of Medicine, Houston, TX) Also in 2008, BCRF researcher Robert Weinberg, PhD, of the Whitehead Institute, Cambridge, MA learned that in the process of metastasis, the cells that make up breast cancer tumors acquire cancer stem cell traits, making them more tenacious. This finding, along with other investigations of the origin of breast cancer stem cells, namely, how tumors seed themselves (Larry Norton, MD, Memorial Sloan-Kettering Cancer Center) and basic molecular research on breast cancer stem cells, makes BCRF a leader in determining the weaknesses of the cells that give rise to breast cancer.
Described by The New York Times as a "breakthrough" treatment for breast cancer, Herceptin's discovery and refinement for various stages and forms of cancer has been an ongoing BCRF endeavor.
Magnetic Resonance Imaging (MRI)
- 2001 NEJM publication describes the value of trastuzumab (marketed as Herceptin), a monoclonal antibody directed against the HER2 receptor that improves outcomes, including survival, for patients with metastatic HER2-positive disease. (Larry Norton, MD, Memorial Sloan-Kettering Cancer Center, co-authored the initial publication)
- 2005 Several large multi-center randomized controlled trials show that adjuvant trastuzumab can decrease the risk of recurrence for patients with HER2-positive early-stage breast cancer by 50 percent. (Edith Perez, PhD, Mayo Clinic, Jacksonville, FL)
- 2007 In the case of inflammatory breast cancer, administering Herceptin before surgery in addition to chemotherapy improves the likelihood of a disease-free survival. (Jose Baselga, MD, Vall d'Hebron University Hospital, Barcelona, Spain)
In 2007, the same year that ASCO and the ACS recommend magnetic resonance imaging (MRI) tests for women considered at high risk for breast cancer and in women with newly diagnosed breast cancer, a specialized MRI test for women with fast-growing breast tumors is developed with BCRF funding (Laura Esserman, MD, MBA, University of California/San Francisco). Tracking the presence of specialized immune system cells always found in the same cellular "neighborhood" where fast-growing tumors occur, BCRF researchers confirmed a new marker for breast cancer screening that may also help doctors better decide which treatments to give patients.
A tumor's blood supply system is one of its most vulnerable points, and a promising new area of cancer research is called anti-angiogenesis treatment. BCRF funded the field's founder, the late Dr. Judah Folkman, MD, of Children's Hospital, Boston from 1998, and helped his and others' laboratories toward the development of multiple drugs that can keep breast cancer cells in a dormant state by inhibiting the growth of blood vessels. (Robert Benezra, PhD, Memorial Sloan-Kettering Cancer Center, New York, Gabriel Hortobagyi, MD, and Mien-Chie Hung, PhD, University of Texas MD Anderson Cancer Center). In 2005, two clinical studies conducted by BCRF researchers showed improved outcomes for breast cancers treated with Avastin, an anti-angiogenesis drug, in conjunction with Taxol. (Kathy Miller, MD, and George Sledge, MD, Indiana University School of Medicine).
In 2006, the development of gene-based approaches to predict which women with breast cancer will benefit most from treatment with tamoxifen or from aromatase inhibitors has improved both the application of aromatase inhibitors and advanced the field of personalized medicine, tailoring treatment to patients' tumors and their individual genetic make up. (Benita Katzenellenbogen, PhD, University of Illinois at Urbana-Champaign, Christos Sotiriou, MD, PhD, Jules Bordet Institute, Brussels, Belgium, and Marc Lippman, MD, University of Miami, FL).
Up to 40 percent of women treated for estrogen receptor-positive (ER+) breast cancer with tamoxifen will progress to incurable disease. In 2007, a genomic test revealed 62 determining genes for ER+ breast cancer and identified two sub-groups of ER+ tumors. (Christos Sotiriou, Institut Jules Bordet). He and his colleagues are improving the selection of patients who will benefit from tamoxifen treatment, and using their new data about different types of ER+ tumors, to develop effective treatments beyond tamoxifen—another improvement in personalized medicine that will save lives. The genomic tests are being translated into commercially viable diagnostic tools for ER+ breast cancers.
Breast Cancer Clinical Trials
BCRF has established a leadership role in breast cancer clinical trials. In 2005, BCRF created the Translational Breast Cancer Research Consortium (TBCRC) (coordinated by Nancy Davidson, MD, and Antonio Wolff, MD, Johns Hopkins University, Baltimore, MD), uniting the efforts of 14 leading breast cancer research centers in the United States. The Consortium's mission is to reduce the burden of breast cancer by using a collaborative and multidisciplinary approach to improve the understanding of breast cancer biology and test new therapeutic strategies. This is a savvy method of extending the value of the field's financial and intellectual resources. After BCRF's founding support, the Komen Foundation and the Avon Foundation joined in and have contributed ongoing support to TBCRC.
- In three years, TBCRC members have completed a study of chemotherapy and a biological agent, cetuximab, for "triple negative" breast cancer, the kind of breast cancer that cannot be treated by current biological agents like endocrine therapy
- Studies examining new combinations of new biological therapies targeting the estrogen receptor and the HER2 proteins have begun.
- Also, work to identify new markers in the blood that might aid in breast cancer management is underway.
Further proof of BCRF's integral support of clinical trials is demonstrated by its grant support of all relevant NCI cooperative groups: the American College of Surgeons Oncology Group, Cancer and Leukemia Group B, the Eastern Cooperative Oncology Group, North Central Cancer Research Group, the Southwest Oncology Group, and the National Surgical Adjuvant Breast and Bowel Project, as well as the oversight group, the Coalition of National Cancer Cooperative Groups.
International Research Funding
In a prescient move, BCRF began a program of international research funding, growing from its first international grant in 2001 to Ephrat Levy-Lahad in Israel, to grants including more than two dozen countries in 2008. While other groups have funded international breast cancer advocacy projects and international research, BCRF was the first private organization to fund scientific research on breast cancer internationally.
- Results include improving standards of care in numerous breast cancer populations in South America, The Middle East and Africa, as well as research breakthroughs in inflammatory breast cancer, breast cancer genetics and the underlying molecular conditions of breast cancer.
- In 2005, The Breast International Group (BIG) in Belgium partnered with The Breast Cancer Intergroup (TCBI). This collaboration--similar to TBCRC, but at an international level--forged new acceleration of clinical trials and translational research drawing from the resources of many countries (Martine Piccart-Gebhart, MD, PhD, TRANSBIG and Jules Bordet Institute, Brussels, Belgium, and Daniel Hayes, MD, University of Michigan, Ann Arbor, MI)
Metabolism, Diet and Physical Activity
Not only have BCRF researchers discovered connections between common nutrients such as vitamin D and disease, they have systematically determined the links between metabolism, diet and physical activity in relation to breast cancer risk, recurrence and survival.
- 1996-2003 BCRF research teams confirm that maintaining a normal body weight can have a profound influence on breast cancer incidence and prognosis, even in genetically pre-disposed women. (Mary-Claire King, PhD, Joan Marks, Pamela Goodwin, MD, University of Toronto/Mount Sinai Hospital, Ontario, Canada, and Stephen Hursting, PhD, MPH, University of Texas at Austin)
- 2006 The discovery that milk consumption increases growth hormone levels, which might explain an association of pre-pubertal dairy intake and breast cancer. (Walter Willett, MD, DrPH, Harvard School of Public Health, Boston).
- 2008 Low levels of Vitamin D are associated with increased risk of breast cancer (Pamela Goodwin, MD).
- 2009 New BCRF studies to determine appropriate levels of vitamin D are beginning, due to the possible risks associated with levels of the nutrient that may be too high.
Science of Survival and Quality of Life
Starting in 2001, the science of survival and quality of life for breast cancer patients is developed with BCRF funding. (Patricia Ganz, MD, University of California, Los Angeles). As more women survive breast cancer, scientific understanding of factors that hinder or enhance survival is crucial. A group of BCRF researchers systematically study exercise, reproductive health and side effects such as lymphedema. Through these studies, they have significantly improved and continue to improve the quality of life for breast cancer survivors. Ganz has also led findings concerning the biological basis for several of the adverse effects of breast cancer treatment: early menopause, fatigue and cognitive problems.
- In a related project begun in 2003, Harold Freeman, MD, of the Ralph Lauren Cancer Center for Cancer Care and Prevention, New York, developed the role of Patient Navigators in the culturally-sensitive coordination of care for women with and at risk for breast cancer.
Different types of cells within the primary tumor, called the tumor microenvironment, can and should be targeted to avoid progression and metastases. In 2007, a progression of breast cancer at the molecular and cellular level known as the epithelial-mesenchymal transition (EMT), a process that allows cancerous cells to invade and metastasize, was identified and described. (Robert Weinberg, Joan Brugge and Charlotte Kuperwasser, PhD, Tufts University School of Medicine, Boston). New therapies designed to impede EMT may avert diseasel progression and metastasis.
Starting in 1998, BCRF researchers have helped reclassify human breast cancers into a greater number of subtypes and in turn established valuable guidelines for treatments according to molecular profiling of tumors. In addition, several BCRF researchers are taking the increased characterization of tumor types and applying their data across populations to determine breast cancer susceptibility. (Charles Perou, Jenny Chang, and Dirk Iglehart, MD, and Andrea Richardson, PhD, Brigham and Women's Hospital/Harvard Medical School, Boston).
In 2003, a novel screening technology was develope--representational oligonucleotide microarray analysis--using biopsied breast tissue that can track the genetic "mistakes" that may lead to cancer with very high accuracy. This ROMA technology is also applied to the differences in the DNA of normal cells, aiding in the search for both tumor differences and individual genetic and metabolic differences that are helping guide breast cancer treatments. (Michael Wigler, PhD, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY).
Breast Cancer Treatment Among The Elderly
Half of all women with breast cancer are 65 or older at diagnosis, and that percentage is known to be rising. Most clinical trials in breast cancer historically exclude women who are considered senior citizens, yet a healthy 65-year-old has a life expectancy of at least another 20 years. Since 1995, BCRF researchers have been studying the needs of elderly breast cancer patients, and documenting the fact that theirs is a unique complex of diseases, and that older patients are less likely to be offered participation in clinical trials than younger patients. The results of one recent study in older women by a BCRF researcher and leader in the area of breast cancer treatment among the elderly show that they are well-served by standard chemotherapy (Hyman Muss, MD, University of Vermont).