Mount Sinai Researchers Discover How Early-Stage Breast Cancer Can Become a Silent Killer in Some Patients
Study finds potential diagnostic biomarkers for patients who could be at risk
Mount Sinai researchers have discovered a previously unknown mechanism in which not-yet-malignant cells from early breast cancer tumors travel to other organs and, eventually, “turn on” and become metastatic breast cancer.
The researchers, who reported in Cancer Research in April, also showed the ability of the transcription factor NR2F1, a protein that controls a gene’s outward expression, to block the pre-malignant cells from ever disseminating, which could be a crucial diagnostic tool to predict relapse.
“The current challenge for the management of treatment of early-stage breast cancer patients (for instance, patients who have non-invasive lesions such as ductal carcinoma in situ), is that even though local invasive recurrences are reduced after surgery or surgery with radiation, the risk of dying from breast cancer remains the same,” said the study’s lead author Maria Soledad Sosa, PhD, Assistant Professor of Pharmacological Sciences, and Oncological Sciences, at The Tisch Cancer Institute at Mount Sinai. “This suggests that before detection and removal of the invasive tumor mass, some pre-malignant cells disseminated and lodged at other sites, waiting for later reactivation. The identification of an ‘early dissemination signature’ in the breast tissue that could identify patients at risk of developing later relapses, who are therefore candidates for systemic therapy, is crucial to reduce mortality in these patients.”
A small but significant percentage of women with early-stage breast cancer never progress into an invasive breast tumor, which is the expected course of metastatic breast cancer. Instead, they die after their pre-malignant lesion reoccurs only in other organs, essentially becoming an unexpected, silent killer. Until this study, the mechanism by which pre-malignant cancer cells acquire mobile and invasive features that allow dissemination and colonization in other organs was not clearly understood.
Researchers used animal models and pre-malignant breast cancer cells from patients, 3D cultures, and high-resolution microscopy to investigate how these pre-malignant cells disseminate. The authors found that the pre-malignant cells downregulated the levels of NR2F1, which helped prompt dissemination along with the upregulation of PRRX1, a master regulator of invasive phenotype.
The authors were able to find pre-malignant cells that simultaneously expressed low levels of NR2F1 and high levels of PRRX1 in patients’ ductal carcinoma in situ tissues, making them a specific pre-malignant subpopulation with potential to disseminate. The clinical significance of this inverse ratio between NR2F1 and PRRX1 needs to be determined within a larger number of human samples and with follow-up studies on overall survival and metastasis-free survival.
Funding for this research included a Susan G. Komen Breast Cancer Foundation Career Catalyst Research Grant and a Breast Cancer Alliance Young Investigator Grant.
About the Mount Sinai Health System
Mount Sinai Health System is one of the nation’s leading integrated academic health systems and one of the largest in the New York metropolitan area. Its comprehensive system includes seven hospitals, more than 400 outpatient practices, over 600 research and clinical laboratories, the Icahn School of Medicine at Mount Sinai, the Graduate School of Biomedical Sciences, and the Mount Sinai Phillips School of Nursing. Together, the Health System comprises approximately 48,000 employees, more than 9,000 physicians, and 8,600 nurses.
As a leading learning health system, Mount Sinai combines clinical expertise with scientific discovery to improve patient care while training the next generation of health care and biomedical leaders. The Health System provides care across every stage of life, from prenatal care through geriatrics, while advancing personalized medicine through artificial intelligence, data science, and biomedical research.
Mount Sinai is consistently recognized among the nation’s leading academic health systems for patient care, research, and education. The Mount Sinai Hospital is ranked No. 1 in New York by Newsweek and No. 5 on the magazine’s World’s Best Hospitals list. The Icahn School of Medicine at Mount Sinai ranks No. 11 among U.S. medical schools and No. 1 among freestanding medical schools for National Institutes of Health funding, reflecting the strength of its scientific enterprise and leadership in biomedical research.
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