Titles and Affiliations
Professor of Medicine, Division of Oncology
Clinical Director, Breast Cancer Program, Division of Oncology
Research area
Advancing precision medicine for patients with estrogen receptor-positive breast cancer.
Impact
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, which aims to develop a biomarker to identify patients with early-stage ER-positive breast cancer who may forego adjuvant (post-surgery) chemotherapy. ALTERNATE trial participants receive neoadjuvant (pre-surgical) endocrine therapy (fulvestrant or the combination of fulvestrant plus anastrozole). 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.
Progress Thus Far
The trial has reached its accrual goal of 1,473 post-menopausal women with Stage II-III ER-positive breast cancer. 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. Molecular analysis of tumor samples from 863 patients demonstrated the significant impact of molecular subtype on sensitivity to combined endocrine therapy (fulvestrant plus anastrazole) compared to anastrazole alone or to chemotherapy. Preliminary analyses have generated promising biomarkers of endocrine therapy resistance and pathways for further investigation.
What’s next
Dr. Ma will continue to collect tumor tissue and blood from study participants during the follow-up period for ongoing analyses. Her goals for the trial are to develop tests that inform which patients do or do not need chemotherapy and to identify what molecular features of ER-positive breast cancer drive therapy resistance.
Biography
Cynthia X. Ma, MD, PhD is a Professor Medicine in the Division of Oncology and the Clinical Director of the Breast Cancer Program in the Division of Oncology at Washington University School of Medicine. 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 the University of Cincinnati. She completed her residency training at New Hanover Regional Medical Center in Wilmington, North Carolina and her fellowship at the Mayo Clinic in Rochester, Minnesota and has been on the faculty at Washington University since 2005.
Dr. Ma 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.
Dr. Ma 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.
