Karla Ballman, PhD

2008-2009 BCRF Project:
Co-investigators: Matthew J. Ellis, MD, PhD, Washington University School of Medicine, St. Louis, MO; Kelly K. Hunt, MD, University of Texas MD Anderson Cancer Center, Houston, TX; and John A. Olson, Jr., MD, PhD, Duke University, Durham, NC

On behalf of the American College of Surgeons Oncology Group
Postmenopausal women with strongly ER-positive stage 2 and 3 breast cancer who are at risk for a mastectomy are candidates for preoperative endocrine therapy to down stage the tumor and improve surgical outcomes. This practice is supported by randomized clinical trials that show an increased chance of breast conservation when aromatase inhibitors were utilized in this indication in comparison with tamoxifen.

In this project, the ACOSOG researchers are using tumor samples from ongoing ACOSOG clinical trial Z1031 to address why estrogen receptor positive breast cancers are not universally responsive to this approach. Specifically, they are asking if large gains in DNA segments in tumor cells called "amplicons" are associated with treatment resistance. This information will not only define which patients are suitable for preoperative endocrine therapy, but will aid in the identification of genes that are responsible for treatment failure.

This may lead to the development of new treatments that increase the effectiveness of endocrine therapy through the application of targeted pharmacological agents. The monthly accrual rate is on target and the trial is estimated to close in summer 2009. The trial continues to provide the availability of pre and post endocrine treatment tissue samples that will allow valuable new insights into the biological basis for the success and failure of endocrine therapy.

Mid-year Progress Report:
The primary objective of the ACOSOG-Z1031 trial is to compare the response rate by clinical examination between three FDA-approved aromatase inhibitors: letrozole, anastrozole and exemestane before surgery in postmenopausal women with clinical stage 2 and 3 ER rich breast cancer.

While clinical response has been used to power most neoadjuvant endocrine therapy trials to date, response by palpation is a problematic primary endpoint that does not provide a very accurate or centrally verifiable assessment of tumor size. Preliminary data from an NCI-funded multicenter Avon/NCI/R01 funded Phase 2 trial of neoadjuvant letrozole led by Dr. Ellis, has shown that image analyses of either digital or digitized mammograms (film mammography scanned by computer), were feasible and robust, providing centrally verifiable and blinded information on the degree of tumor response within the breast.

Since these films are already collected as part of the standard of care, and therefore the data can be made available at minimal cost to the research budget, this proposal supports the validation of digital mammogram response (DMR) measurements, as a novel and robust indicator of tumor response. Patient accrual has now reached over 80% of the target goal with 304 patients enrolled to date at 49 sites and is anticipated to close in September 2009. Specimen acquisition is also going according to plan.

Bio:
Dr. Ballman received her PhD from the Massachusetts Institute of Technology in 1991. Since then, she has been a consultant for the Software Research group at AT&T Bell Labs in Naperville, IL, been a faculty member of the Department of Mathematics and Computer Science at Macalester College in St. Paul, MN and been a faculty member in the Department of Statistics at the University of Auckland in New Zealand. Dr. Ballman joined the Division of Biostatistics at Mayo Clinic in 1999 where she now serves as the Division Chair.

The primary research interests of Dr. Ballman are clinical trial design and analysis and the analysis of high-dimensional data. She is the group statistician and director of the Statistics and Data Center for the American College of Surgeons' Oncology Group (ACOSOG).