Titles and Affiliations
Assistant Professor of Hematology and Oncology
Department of Medicine
American Association for Cancer Research
Research Area
Developing a blood-based test to predict treatment resistance in estrogen receptor-positive metastatic breast cancer, with a focus on the understudied lobular subtype.
Impact
Estrogen receptor (ER)-positive metastatic breast cancer (MBC) affects an estimated 120,000 women in the U.S. Of these patients, only about 30% survive five years after diagnosis, largely because the disease eventually becomes resistant to estrogen-blocking endocrine therapy, the standard treatment. Invasive lobular carcinoma (ILC), a subtype making up about 15% of breast cancer cases, is treated identically to the more common ductal subtype despite behaving quite differently—it tends to recur later, spread to different organs, and lead to shorter survival once it progresses. Dr. Sharifi’s team has utilized a liquid biopsy approach to track estrogen activity and treatment-resistance mutations successfully collecting tumor cells from over 80% of blood samples in a pilot study. They observed a correlation between estrogen activity within the circulating tumor cells with better patient outcomes, and that estrogen activity was notably lower in tumor cells from lobular cancer than from ductal cancer, a finding that may help explain why lobular cancer carries a worse prognosis.
What’s Next
Building on these findings, Dr. Sharifi will use her AACR/BCRF research award to study 100 patients with ER-positive MBC, split evenly between lobular and ductal cancer, as they begin endocrine therapy, to determine whether blood-based measures of estrogen activity can predict how well lobular cancer patients respond to treatment, and to identify the genetic and molecular differences driving resistance in lobular versus ductal disease. If successful, this blood-based test could identify patients likely to resist endocrine therapy early enough to offer them more effective alternative treatments, while also revealing new molecular targets for drug development in lobular breast cancer specifically.
Biography
Marina Sharifi, MD, PhD completed her training in cancer biology at the University of Chicago followed by internal medicine residency, medical oncology fellowship and post-doctoral research in the University of Wisconsin Physician Scientist Training program. In 2022, she joined the University of Wisconsin, Madison faculty as an Assistant Professor in the Department of Medicine, Division of Hematology, Oncology and Palliative Care. Her clinical focus is in medical oncology, and her lab leverages translational multiomic approaches to identify molecular drivers of targeted therapy response and resistance in patients with breast and prostate cancer.
