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Cynthia X. Ma, MD, PhD

Professor of Medicine
Division of Oncology
Section of Medical Oncology
Washington University School of Medicine
St. Louis, Missouri

Current Research

Goal: To advance the use of precision medicine for patients with estrogen receptor (ER)-positive breast cancers.

Impact: Drs. Ma and Ellis are conducting a trial to test a predictive tool that identifies patients with ER-positive breast cancer who are at low risk of recurrence and may safely avoid chemotherapy following surgery. Their work could spare many from the toxicities of chemotherapy and lead to more personalized treatments.

What’s next: The team will continue to collect tumor and blood for molecular studies in patients enrolled in the trial.

Treatment with endocrine (anti-estrogen) therapy is successful in treating most breast cancers, but about 20 percent of women will experience a recurrence of their disease. Unfortunately, there is currently no way of predicting which patients will respond to endocrine therapy and which will not. Drs. Ma and Ellis are conducting a clinical trial to test a predictive index to identify patients who may be spared chemotherapy.

Full Research Summary

Research area: To identify biomarkers that can predict response to anti-estrogen (endocrine) therapies.

Impact: Estrogen receptor (ER)-positive breast cancer typically responds well to surgery and endocrine therapy. However, up to 20 percent of patients will experience a recurrence. It is therefore important to identify biomarkers that can identify those patients whose tumors are most likely to respond to endocrine therapy versus those that most likely will not. Drs. Ma and Ellis are analyzing a large number of patient blood and tumor samples to identify such biomarkers with the goal of developing better risk stratification and treatments.

Current investigation: The research team has completed patient accrual for the ALTERNATE trial. They will use data obtained from ALTERNATE to better understand how resistance to endocrine therapy occurs so better treatments can be developed, to identify patients at low risk of recurrence who do not need chemotherapy after surgery, and to develop a mutation-based classification of ER-positive breast cancer for targeted therapeutic intervention. In addition, they will continue to assess the utility of circulating tumor DNA in predicting late recurrence and endocrine therapy resistance.

What she’s learned so far: Dr. Ma’s analysis of the data from over 1000 patients has provided insight into a marker of the effectiveness of chemotherapy, called Ki67.

What’s next: The team will continue to analyze tumor samples obtained from patients enrolled in ALTERNATE trial, in particular, for Ki67 – a marker of cell proliferation – and estrogen receptor expression. Furthermore, they will continue to conduct molecular analysis on tissue biopsies and blood.

Biography

Dr. Ma is a physician scientist with a research focus in breast cancer biomarker and targeted therapeutics development.  Dr. Ma received her medical degree from Beijing Medical University and earned her PhD in developmental biology from University of Cincinnati. She completed her post-doctoral training at New Hanover Regional Medical Center in Wilmington, North Carolina and her fellowship at the Mayo Clinic in Rochester, Minnesota.  She has been on faculty at Washington University since 2005. She is the Clinical Director of the Breast Cancer Program in the Section of Medical Oncology, Division of Oncology at Washington University. She has designed and conducted a number of mechanism-based early phase trials of novel agents, including UCN-01, BKM120, MK-2206, palbociclib, IMC-A12, temsirolimus, neratinib, among others, in patients with resistant breast cancer.  She led a phase II trial of neratinib for patients with metastatic HER2 mutated breast cancer (MutHER trial) and demonstrated the activity of neratinib in this patient population.  In collaboration with NCI and CTEP, she contributed to the development of several small molecule inhibitors, including MK2206 and temsirolimus, which target the PI3K/AKT/mTOR pathway in overcoming endocrine resistance, in addition to a phase I/II trial that evaluated the potential of cixutumumab, an IGF-1R antibody, in restoring mTOR inhibitor efficacy in metastatic hormone receptor positive breast cancer.  She also led the phase II neoadjuvant trial of MK2206 in combination with anastrozole in patients with newly diagnosed clinical stage II to III estrogen receptor positive breast cancer.  She is the study chair for the ongoing phase III Alliance trial A011106 (ALTERNATE trial) to validate neoadjuvant biomarker endpoint as surrogate markers of long-term outcome and to investigate endocrine resistance mechanisms for estrogen receptor positive breast cancer.  Her laboratory has focused on biomarkers and resistance mechanisms for agents that target cell cycle and PI3K pathway through analysis of clinical specimens and preclinical studies using breast cancer cell lines and patient-derived xenograft models.

BCRF Investigator Since

2012

Area(s) of Focus