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Nadine M. Tung, MD
Director, Cancer Risk and Prevention Program
Beth Israel Deaconess Medical Center
Associate Professor of Medicine
Harvard Medical School
- Seeking biomarkers to guide treatment decisions in triple negative and BRCA-driven breast cancers.
- A clinical trial is ongoing to compare a platinum-based therapy to standard chemotherapy in patients with a mutation in the BRCA genes.
- This trial will help to determine which patients are most likely to benefit from a common drug, called cisplatin, and advance effective therapies in these aggressive breast cancers.
Mutations in the BRCA genes–drivers in hereditary breast cancer–affect the cell’s ability to repair DNA damages. While this defect leads to breast (and other forms of) cancers, it also makes BRCA-mutated cells vulnerable to treatments that cause DNA damage. Cisplatin is a commonly used chemotherapy drug that causes a type of DNA damage that BRCA-deficient cells cannot repair. Drs. Tung and Schnitt are leading a clinical trial to compare cisplatin to standard chemotherapy in women with early stage breast cancer and mutations in the BRCA genes.
Full Research Summary
Triple negative breast cancer (TNBC) comprises approximately 15 percent of all breast cancer and is the most common breast cancer type caused by mutations in the BRCA genes. The clinical management of TNBC and other BRCA-related breast cancers is challenging due to the often aggressive behavior and lack of targeted therapies.
Cisplatin causes a type of DNA damage that cannot be repaired by cells that are defective in DNA repair, leading to tumor cell death. Many TNBCs and all BRCA-driven breast cancers share this defect, making cisplatin a promising therapy for these cancers. While not typically used to treat breast cancer, cisplatin has demonstrated promising results in clinical trials with breast cancer patients that are BRCA mutation carriers.
The INFORM trial (NCT01670500) is a randomized clinical trial designed to compare the relative effectiveness of cisplatin and standard chemotherapy in women with early-stage breast cancer who have inherited BRCA mutations. The trial is being conducted at the Dana-Farber Harvard Cancer Center, as well as eight sites outside of Boston, including three through the Translational Breast Cancer Research Consortium (TBCRC).
The investigators are in the process of collecting research biopsies and blood samples that will be used to determine which patients respond better to each therapy. One hundred six patients out of a target accrual of 170 are enrolled.
Nadine Tung, MD is the Director of the Cancer Genetics and Prevention Program at Beth Israel Deaconess Medical Center (BIDMC) which she established in 1997 to evaluate patients and families with hereditary cancer syndromes. She is also a breast medical oncologist and a member of the Dana-Farber Harvard Cancer Center as well as an Associate Professor at Harvard Medical School. She graduated from Princeton University in 1980 and Harvard Medical School in 1984.
Dr. Tung's research focuses on hereditary causes of breast cancer as well as effective strategies for breast cancer prevention and treatment. Much of her research has focused on women with BRCA1 and BRCA2 mutations, studying the genetic and environmental factors that influence cancer development as well as the biology and prognosis of the breast cancers they develop. Through BCRF, she is overseeing a multi-center, national trial evaluating whether cisplatin is superior to standard chemotherapy for women with BRCA1/2 mutations and newly diagnosed breast cancer. Her research also focuses on identifying other inherited gene mutations that predispose to breast cancer. Other areas of Dr. Tung’s research include evaluating the prognosis and optimal treatment of triple negative breast cancer. Dr. Tung serves on the Editorial Board of the Journal of Clinical Oncology as well as the American Society of Clinical Oncology’s Cancer Prevention Committee and Cancer Genetics Subcommittee.