Associate Professor, Medicine
Division of Oncology
Section of Medical Oncology
Washington University School of Medicine
St. Louis, Missouri
Seeking to advance precision medicine for patients with estrogen receptor-positive breast cancers.
A phase III trial is ongoing to test a predictive assay to select patients who can safely forego chemotherapy after surgery.
These efforts could lead to personized treatments, sparing many women the toxicities of chemotherapy, and new targeted therapies to reduce the use of chemotherapy.
Although the majority of estrogen receptor-positive (ER+) breast cancers are treatable with anti-estrogen (endocrine) treatment and chemotherapy, up to 20 percent of patients will recur with metastatic disease. On the other hand, many patients can be cured with endocrine treatment alone and can be spared the toxicities of chemotherapy.
A major task is to develop biomarkers that identify those breast cancers most likely to respond to anti-estrogen therapies vs. those that are resistant.
BCRF has provided critical support for National Cancer Institute-sponsored Cooperative Group neoadjuvant trials in women with ER+ breast cancers. In addition to providing critically important information to guide the development of individualized treatment strategies and targeted therapies for this patient population, these studies also generate a rich source of tumor material to investigate why some tumors are resistant to treatment.
One such trial is the ALTERNATE trial, led by Dr. Cynthia Ma and BCRF co-investigator, Dr. Matthew Ellis under the auspices of the Alliance for Clinical Trials in Oncology, one of the NCI cooperative groups. The overarching objective of this Phase III neoadjuvant treatment trial is to validate a test called modified Preoperative Endocrine Prognostic Index (PEPI) in predicting endocrine therapy sensitivity and to develop a mutation-based classification of ER+ breast cancer that will inform new approaches to reduce the recurrence rate.
As of May 2017, the study has enrolled 789 patients, over 700 of whom received study test results that helped to individualize their treatments. DNA and RNA were extracted from samples from 490 patients, and sequencing analysis is in progress for the first 253 patients.
In the coming year, the trial investigators will continue to enroll patients towards a target enrollment of 1455 patients, and process the samples for biomarker and genomic studies. This research has the promise to change the clinical management of ER+ breast cancer and lead to more personalized treatments.
Dr. Cynthia Ma obtained her MD from Beijing Medical University in China and subsequently PhD in Developmental Biology from the University of Cincinnati. She completed her Internal Medicine residency from New Hanover Regional Medical Center at North Carolina followed by the Hematology/Medical Oncology fellowship at Mayo Clinic, Rochester, Minnesota. In 2005, she was recruited as a breast oncologist at Washington University School of Medicine (WUSM). She is currently an Associate Professor of Medicine and a research member of Siteman Cancer Center. In August 2014, Dr. Ma was appointed as the Clinical Director of the Breast Cancer Program at WUSM. Dr. Ma’s research includes preclinical and clinical trial development of molecularly targeted cancer therapeutics for the treatment of resistant breast cancer. She is the principal investigator for several biomarker directed clinical trials of biological agents including UCN-01, temsirolimus, MK2206, BKM120, IMC-A12, and palbociclib in breast cancer.