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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
Goal: To determine which patients with early-stage, BRCA-driven breast respond best to chemotherapy.
Impact: Drs. Tung and Schnitt completed a clinical trial that compares the effectiveness of standard chemotherapy to the chemotherapy drug cisplatin in early-stage breast cancer patients who have inherited mutations in the BRCA1 and BRCA2 genes. Their findings could help identify which patients will benefit from cisplatin, which is typically not used to treat breast cancer.
What’s next: Having completed the trial, Drs. Tung and Schnitt are now analyzing samples from the patients enrolled in the study to look for biomarkers that predict which patients respond best to each therapy.
Normally, BRCA genes produce proteins that help repair DNA damage. But this function is impaired in individuals who have mutations in these genes, which leads to breast and other forms of cancer. However, this makes BRCA-mutated cells vulnerable to treatments that cause DNA damage. Research suggests that the chemotherapy drug cisplatin may be effective in treating patients with BRCA-driven breast cancers because it causes a type of DNA damage that BRCA-deficient cells can’t repair. Drs. Tung and Schnitt aim to determine if biomarkers can predict whether cisplatin or standard chemotherapy would be better to treat BRCA carriers with newly diagnosed breast cancer.
Full Research Summary
Research area: Determining the best treatment options for patients with inherited BRCA mutations and newly diagnosed breast cancer.
Impact: Drs. Tung and Schnitt recently completed a randomized clinical trial that showed that cisplatin and standard chemotherapy agents (i.e. doxorubicin and cyclophosphamide, AC) are both effective in women with early-stage breast cancer with inherited BRCA1/2 mutations. Analyses of specimens collected could uncover valuable markers of treatment response that may inform difficult treatment decisions for breast cancer patients with inherited BRCA1/2 mutations.
Current investigation: Drs. Tung and Schnitt are working with Dr. Judy Garber—and teams from Boston and medical institutions across the country through the Translational Breast Cancer Research Consortium (TBCRC)—to collect and analyze samples from a rare group of breast cancer patients. Blood and tumor specimens from BRCA mutation carriers will be analyzed to identify markers that distinguish those who do better on cisplatin, when compared with standard chemotherapy treatment.
What they’ve learned so far: Drs.Tung and Schnitt have completed a randomized phase II clinical trial called INFORM (NCT01670500) to compare the efficacy of cisplatin and standard chemotherapy agents, doxorubicin and cyclophosphamide (AC), in women with early-stage breast cancer who have inherited BRCA1/2 mutations. The INFORM study showed that:
- Cisplatin is active in treating breast cancer in BRCA mutation carriers
- Patients with TNBC or ER-positive BRCA-associated breast cancer did not respond better to cisplatin than to AC.
- Tumor responses seen are due to DNA damaging chemotherapy in general, and not specifically cisplatin.
What’s next: Drs. Tung and Schnitt will analyze specimens from the INFORM trial to identify molecular markers that distinguish those who do better on cisplatin compared to AC, standard chemotherapy treatment. The team plans to use artificial intelligence to evaluate pre-treatment tumor specimens to explore whether there are indicators of which tumors will respond well to treatment.
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.