Michaela Higgins, MD, BCh

2009-2010 BCRF Project
ASCO Cancer Foundation 2009 Young Investigator Award (the Hirschhorn Award, in honor of Susan B. Hirschhorn and in memory of her mother, Ellen S. Hirschhorn)

Hormonal manipulations, such as tamoxifen, have improved breast cancer-related disease free and overall survival. Such approaches are limited to patients with hormone receptor-positive disease (about two-thirds of all breast cancers) and loss of sensitivity to hormonal manipulations is a common problem in breast cancer clinics.

Data from Dr. Higginss laboratory suggest that novel agents such as the histone deacetylase inhibitor (HDACI) vorinostat, can cause re-expression of the estrogen receptor (ER) and can induce tamoxifen sensitivity in breast cancer cells that did not express ER originally. She hypothesizes that this effect, if also apparent in her clinical study with real breast tumors, would widen the range of breast cancer patients that could benefit from treatments like tamoxifen.

She will do a phase II study which will enroll women with newly diagnosed early breast carcinoma. The women will receive vorinostat 400mg and tamoxifen 20mg, each one pill daily, for the 14 days preceding their planned surgery. Using samples taken from the women's original biopsy and a sample taken from their mastectomy or lumpectomy specimen after treatment, Dr. Higgins's team will compare levels of ER and demonstrate whether or not this novel treatment has changed how quickly the tumor cells are growing. The goal is to provide the rationale for the addition of HDACI to tamoxifen to breast cancer patients who have failed prior hormonal manipulations, or to patients with ER-negative tumors, thus potentially restoring hormone sensitivity and broadening treatment options for breast cancer patients.

Mid-Year Progress Report:
The trial design and protocol were further refined over the summer and fall. Merck has agreed to provide vorinostat to patients. The trial passed through the Johns Hopkins Clinical Research Committee in early January 2010. Dr. Higgins hopes to proceed to IRB soon and to open for accrual in the spring of 2010.

Bio:
Dr. Higgins attended medical school at University College Dublin in her native Ireland. She completed her residency in Dublin and trained for two years as a fellow in Medical Oncology in Ireland before applying successfully to the Medical Oncology Fellowship Program at the Johns Hopkins School of Medicine and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.

Early in her oncology training, Dr. Higgins decided to focus on translational breast cancer research. She has been mentored closely by Dr. Vered Stearns and has developed a clinical protocol that seeks to study possible mechanisms of overcoming resistance to commonly used hormonal therapies in breast cancer. This study has the potential to broaden treatment options for breast cancer patients who have either become resistant to hormonal therapies, or have breast cancers that do not express hormone receptors. Her work is supported by the American Society of Clinical Oncology Young Investigator Award.

Dr. Higgins is currently Chief Fellow of the Johns Hopkins Medical Oncology Fellowship Program. As she moves forward as an independent translational breast cancer researcher Dr. Higgins hopes to collaborate with investigators both in the USA and abroad to improve outcomes for breast cancer patients worldwide.