Science is amazing. It used to be a breast-cancer diagnosis was terminal. But advances in treatment led to powerful chemotherapy that can knock out the cancer. This same treatment also deteriorates critical organs. How much to give is the key to balancing survival and quality of life. Unfortunately, it’s unclear whether current guidelines are optimal for obese patients who are at increased risk of harmful side effects from chemotherapy. University of Iowa (UI) College of Pharmacy Associate Professor Mary Schroeder, part of the Health Services Research division of the College’s Pharmacy Practice and Science Department (PPS), hopes she and her team can change that through a four-year, $2.24 million grant she recently was awarded.
Schroeder is principal investigator, alongside Joan Neuner of the Medical College of Wisconsin, for the project, titled “Chemotherapy Dosing in Patients with Obesity: Are Oncologists Optimally Balancing Risks and Benefits to Avoid Overtreatment and Undertreatment?” It is sponsored by the United States (U.S.) Department of Defense’s (DOD) Congressionally Directed Medical Research Program.
One Size Does Not Fit All
According to the American Cancer Society, breast cancer is the most common type of cancer for women in the U.S., accounting for about 30% (1 in 3) of all new female cancers annually. Furthermore, the organization estimates that during 2023, nearly 300,000 new cases of invasive breast cancer will be diagnosed, making it the most common new cancer diagnosis in men or women. Additionally, the Centers for Disease Control and Prevention reports obesity affects nearly 42% of U.S. adults, a condition that increases breast-cancer risk.
“The challenge is that the clinical trials (for chemotherapy) 50 years ago never tested on obese individuals, like we have today, or multiple doses. They only tested one dose on subjects that were the exact same in health and saw that it worked,” Schroeder said.
Current chemotherapy dosing guidelines are by height and weight. So, those with a higher Body Mass Index get a bigger bag of chemo. The total dose is broken down across multiple infusions. As soon as the body can handle the next portion, the patient gets it. But, comorbid factors are unaccounted.
“The problem is if you have cancer, you’re going to get this really powerful chemo to kill the cancer cells. It may also kill you and will almost surely make you very sick. It’s not clear how much to give a person,” Schroeder said. “People with obesity often have organ dysfunction already, such as heart disease and diabetes, and chemo only adds to the destruction of those organs. Doctors may give these patients less than guidelines recommend to prevent life-threatening toxicity. It’s not necessarily a bad decision, but the challenge is that guidelines don’t clearly state when and how much to dose reduce for developed or expected toxicity.”
She added any disruption during treatment, including hospitalizations due to fever, anemia, neutropenia, infection, dehydration, or other conditions can delay the next chemo infusion and make it more likely the patient won’t get the full dose. Obese individuals are at higher risk for such adverse effects.
Data Comparisons
This observational project aims to find answers to disparities in breast-cancer treatment by comparing the use of chemo and its outcomes in current practice for breast-cancer patients with and without obesity.
Schroeder and her colleagues are looking at more than 10 years of electronic health data (EHR) from the Greater Plains Collaborative (GPC), a member of The National Patient-Center Clinical Research Network (PCORnet®). The GPC currently includes 13 medical centers across eight states and is committed to improving health-care delivery through ongoing learning, adoption of evidence-based practices, and active research dissemination. The UI is a GPC founding member site.
Schroeder’s research interests are rooted in cancer and her DOD grant is a lesson in perseverance. In 2017, the GPC put out a call for using accumulated EHR data in a pilot project. Schroeder applied and got it. She then submitted grant applications to the National Institutes of Health in 2019, 2020, and 2022 seeking funding for her chemotherapy and obesity study with no success. Schroeder finally landed the DOD Breakthrough Award in 2023. The government entity is interested because military active-duty women are at a 40% higher risk of breast cancer than the general population.
“The grant is really a validation of the work I’ve been doing for years,” Schroeder said. “I think there’s a real research gap, and potential harm we could be doing to patients if we are not more careful about understanding the optimal amount of chemo, especially for patients with obesity.”
Donald Letendre, dean of the College, noted Schroeder’s persistence is “a wonderful example for others.”
Other UI-affiliated team members include Assistant Professor Cole Chapman, Clinical Assistant Professors Lorin Fisher and Michelle Schmidt, and graduate students Nikita Nikita, and Brahmendra Viyyuri from the College of Pharmacy; College preceptor Dana McDougall of MercyOne Waterloo; Betsy Chrischilles (’79 BSPh, ’81 MS, ’86 PhD), professor and head of the Department of Epidemiology, Pomerantz chair in Public Health, and director - Health Effectiveness Research Center; and Brad McDowell, director of the Holden Comprehensive Cancer Center Population Research Core.
“We are excited to have Dr. Schroeder lead this project,” said Jay Currie, clinical professor and PPS department chair. “The team she has assembled emphasizes the essential role of clinical pharmacists in the management of cancer patients. It has the potential to change practice.”
Ultimately, Schroeder and colleagues hope their research will provide evidence for more nuance in guideline recommendations and prompt future studies examining how other specific diseases also impact chemotherapy dosing.
“We want to improve patient lives by giving them the right amount of chemo to maximize their survival, while also giving them the best quality of life during and after treatment,” she said.