Discovery of Root Cause of Triple-Negative Breast Cancer May Lead to New Therapies
TNBC comprises about 15-20 percent of all breast cancer diagnoses; disproportionately affects women of African and Hispanic descent.
Targeted therapies to treat triple negative breast cancer (TNBC), an aggressive, highly-metastatic disease that comprises about 20 percent of breast cancer incidences and which cannot be treated with conventional methods, may soon be realized, say researchers from the Icahn School of Medicine at Mount Sinai. Their study, titled "Disrupting the Interaction of BRD4 with Diacetylated Twist Suppresses Tumorigenesis in Basal-like Breast Cancer," recently published in the journal Cancer Cell, demonstrated that a newly-developed small molecule treatment could disrupt the cellular process that causes tumors and the spread of TNBC, an inflammation-associated cancer.
The research team included scientists from Mount Sinai, the University of Kentucky, M.D. Anderson Cancer Center, and the Sun Yat-sen University Cancer Center and Soochow University in China; it was led by Ming-Ming Zhou, PhD, Professor and Chair of the Department of Structural and Chemical Biology at the Icahn School of Medicine at Mount Sinai.
"In this study, using a mouse model for human breast cancer, we showed that TNBC's characteristics -- rapid tumor growth and metastasis -- is heavily dependent upon and fueled by markedly evaluated transcriptional activation of pro-inflammatory cytokines and chemokines," said Dr. Zhou. "Using a small molecule to target that gene transcriptional machinery, we further uncovered and validated a drug target for potential new treatment of TNBC, which account for more than 170,000 new breast cancers annually and which disproportionately affects women of African and Hispanic descent. While much more research needs to be done, our findings are very promising and give us hope in the overall war against breast cancer."
TNBC comprises all forms of breast cancer that lack the expression of three key cell-surface receptors, i.e. estrogen receptors (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2/neu). Currently, available treatments for breast cancer target only these receptors, and thus are not applicable to TNBC patients. TNBC is highly aggressive, highly metastatic, and much more likely to recur than other subtypes of breast cancer. The current standard of care for TNBC is surgery with adjuvant chemotherapy and radiation therapy, which is toxic to living cells and ineffective once the tumor has spread.
Key facts about TNBC:
• TNBC comprises about 15 to 20 percent of breast cancer incidences
• In 2012, the most recent year for which data is available, about 170,000 new cases of TNBC were reported worldwide
• TNBC disproportionately affects women of African and Hispanic descent
• TNBC occurs more often in younger women and affects women as early as in their 20s
• About 80 percent of breast cancer in people with an inherited BRCA1 mutation – the gene which increases one's risk of developing breast and ovarian cancer – are found to have TNBC
About the Mount Sinai Health System
The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services—from community-based facilities to tertiary and quaternary care.
The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is in the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals."