Washington University School of Medicine
St. Louis, Missouri
Professor of Medicine, Division of Oncology
Section of Medical Oncology
Advancing the use of precision medicine for patients with estrogen receptor-positive breast cancer.
Estrogen receptor (ER)-positive breast cancer typically responds well to endocrine therapy. However, up to 20 percent of patients will experience a recurrence. Dr. Ma is conducting a clinical trial called ALTERNATE (NCT01953588), which aims to develop a biomarker that can predict the long-term outcome of patients with ER-positive breast cancer receiving neoadjuvant (pre-surgical) endocrine therapy (fulvestrant or the combination of fulvestrant plus anastrozole) to identify those who may forego adjuvant (post-surgery) chemotherapy. The study is following patients for ten years after surgery or until the patient experiences a recurrence. Results from the study could spare many from the toxicities of chemotherapy and lead to more personalized treatments.
The trial has enrolled 1,473 post-menopausal women with Stage II-III ER-positive breast cancer and all patients have completed surgery and entered the adjuvant phase. Dr. Ma is performing ongoing molecular analyses of participant blood and tumor samples to identify resistance mechanisms and novel drug targets. She and her team have validated a hormone receptor-based biomarker model called PEPI that predicts response to endocrine therapy in postmenopausal women with ER-positive, HER2-negative, locally advanced breast cancer. They have discovered from molecular analysis of tumor samples that the combined endocrine therapy (fulvestrant plus anastrazole) was more effective in suppressing tumor cell growth than either drug alone for luminal B, but not luminal A breast cancers. In addition, they found that non-luminal breast cancers were often resistant to neoadjuvant endocrine therapy but more sensitive to chemotherapy.
Dr. Ma will continue to obtain and perform analyses on tumor biopsy and blood samples from study participants during the follow-up period. Her team will test blood samples for biomarkers at year five post-surgery and at serial time points up to ten years for high-risk patients and at recurrence to identify biomarkers that will be able to predict risk for late recurrence in this patient population.
Cynthia X. Ma, MD, PhD 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 the 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 several 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.
Since the trial activation in December 2013, BCRF has provided critical support for research sample acquisition, processing, and analysis.
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