Kathy D. Miller, MD

2012-2013 BCRF Project:
(made possible by generous support from ANN INC.)

1) (made possible with generous support from ANN INC.)
Patients frequently report "fatigue" as a consequence of breast cancer therapy but the true impact of various cancer treatments on a patient's daily activities (the amount of energy they use) and their physical fitness (power generation) has not been measured. Working with an exercise physiologist, Dr. Miller and her team will launch a new study using state-of-the-art technology to measure the impact of various treatments, including surgery and radiation, anti-estrogen drugs, and chemotherapy, during the first year after diagnosis. They will evaluate both the impact of acute treatment and the degree of spontaneous recovery. In addition, Dr. Miller's study will explore the relationship of these energy parameters to changes in insulin resistance, body mass index, body composition, and patient-reported physical activity, fatigue, and overall quality of life.

While a recommendation for exercise is easy to make, healthcare providers have little (if any) experience in assessing a patient's baseline energy expenditure or exercise capacity. Energy expenditures that are moderate for one group (the physically fit subset) may present risk or potential harm to another. Interventions will therefore need to take into account each patient's baseline energy expenditure and power generation, as well as the expected impact of her treatment plan. Only by understanding the impact of therapy can scientists develop tailored and individual interventions to improve the health of breast cancer survivors.

Mid-year Progress: Working with an exercise physiologist, Dr. Miller's team continues to develop their pilot study assessing the impact of various treatments including surgery and radiation, anti-estrogen drugs, and chemotherapy during the first year after diagnosis and to evaluate both the impact of acute treatment and the degree of spontaneous recovery. Their study also explores the relationship of these energy parameters to changes in insulin resistance, body mass index (a measure of obesity), body composition, and patient reported physical activity, fatigue, and overall quality of life. The investigators also continue to develop an effective intervention that takes into account each patient's baseline energy expenditure and power generation, as well as the expected impact of her treatment plan.

2) On behalf of Coalition of Cancer Cooperative Groups
Co-Investigators: Robert L. Comis, MD, Coalition of Cancer Cooperative Groups, Philadelphia, PA and Joseph A. Sparano, MD , Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY

In a separate project, Dr. Miller will be participating in a study by the Coalition of Cancer Cooperative Groups. National Cancer Institute (NCI) statistics as of January 2009 reveal that there were over 2.7 million women alive in the United States, who have a history of cancer of breast cancer. Approximately 30% of these women already have, or will eventually develop recurrence and incurable metastatic disease. Late relapse, which is defined as occurring five or more years after an initial diagnosis of operable breast cancer, accounts for up to one-half of all breast cancer recurrences. It is difficult for researchers to study tumor and host-associated factors driving late recurrence because of the lack of adequate biospecimens (i.e. primary and metastatic tumor specimens, blood specimens, and germline DNA) linked to clinical data with sufficiently long follow-up. Further complicating this issue, late recurrence may be driven by dynamic rather than static host factors that may wax or wane with time and thus require serial biospecimen collection at diagnosis, before recurrence, and at recurrence, rather than the usual paradigm of collecting biospecimens only at diagnosis.

Although late relapse has been recognized as a major clinical problem, accounting for up to one-half of all relapses in estrogen receptor positive (ER+) disease, it also may occur unpredictably in other breast cancer subtypes. For example, when evaluating patterns of recurrence in 4,950 eligible patients enrolled in the E1199 trial who received adjuvant chemotherapy (plus endocrine therapy if ER+), the annual hazard rate (HR) of recurrence within the first five years of diagnosis was about three-fold higher for patients with triple negative breast cancer (TNBC), and two-fold higher for HER2 positive (HER2+) breast cancer (before the use of adjuvant trastuzumab or Herceptin®), compared with ER+ and/or progesterone positive, HER2-negative disease, but was higher for ER+/PR+ disease compared with other subtypes beyond five years, In addition, recurrence risk persisted over time for all subtypes after five years. Moreover, host factors such as body mass index (BMI) at diagnosis may contribute to late relapse, especially in ER+/PR+ disease. Two prior reports have found a similar association between obesity and recurrence specifically in ER-positive disease, but this study indicates that obesity is specifically associated with late recurrence.

There are no clinical or pathologic features predictive of late relapse; gene expression assays predict earlier recurrences. Although extended adjuvant therapy with an aromatase inhibitor given for up to five years after two to five year course of tamoxifen therapy has been shown to reduce the risk of recurrence in ER-positive disease, the absolute benefits are low, resulting in many patients receiving unnecessary therapy. The overall aims of this multi-institutional, multi-year trial, therefore, are to: (1) create a plasma/serum biorepository for evaluating determinants of late relapse; (2) create a biorepository of metastatic tumor samples in patients who have had a late relapse; (3) determine body mass index (BMI) and co-morbidity burden in patients with operable breast cancer 5 or more years after diagnosis, and (4) determine whether there is a relationship between late relapse and BMI at diagnosis and at 5 years after diagnosis, and whether BMI-associated inflammatory and/or metabolic biomarkers are associated with early and late recurrence.

Mid-year Progress: The Coalition of Cancer Cooperative Groups reports that the establishment of a Late Relapse Biorepository is proceeding as scheduled. Presently, the protocols for the TAILORx and E5103 studies, which form the basis for this endeavor, have been modified to allow patients participating in the original studies to enroll in this new research study if eligibility requirements are met. Recruitment efforts will commence in March 2013, immediately following February activation of the amended protocols. All processes and procedures are in place.

Bio:
Dr. Kathy Miller is Associate Professor and Sheila D. Ward Scholar at the Indiana University School of Medicine, Division of Hematology/Oncology. She is an active member of the American Society of Clinical Oncology, the Eastern Cooperative Oncology Group and the Hoosier Oncology Group.

She received her bachelor of science degree in biology magna cum laude from the University of Miami, Coral Gables, Florida, and her medical degree from Johns Hopkins School of Medicine in Baltimore, Maryland. She completed her internship as well as her residency at Johns Hopkins School of Medicine followed by a Hematology/Oncology fellowship at Indiana University.

Her research interests focus on the role of angiogenesis in breast cancer. This interests spans departmental boundaries and has taken several forms: laboratory evaluation of the modalities that measure tumor-associated vasculature, and clinical trials of anti-angiogenic agents.