Feature Stories
Jorge Salazar
Conquering Breast Cancer
Supercomputers give scientists the resources and tools needed to treat the disease
Breast cancer leads worldwide among cancers in women, claiming nearly 670,000 lives in 2022 according to the World Health Organization.
TACC supercomputers give scientists the computational resources and data analysis tools needed to make new discoveries in understanding and treating the disease. The following examples illustrate where advanced computing is making strides to help conquer breast cancer.
Digital Twins in Oncology
Mathematical modeling is improving predictions of how triple-negative breast cancer (TNBC) tumors will respond to treatment, according to research led by Tom Yankeelov of the Oden Institute for Computational Engineering and Sciences at UT Austin. TNBC is aggressive with fewer treatment options, and is more common in Black women and all women under 40.
“TACC has been there every step of the way as we develop methods for improving the treatment of—and outcomes for—patients battling cancer.”
These cells lack three commonly overexpressed biomarkers in breast cancer: estrogen receptors, progesterone, and the human epidermal growth factor receptor 2 (HER2).
Yankeelov co-authored a 2022 study published in the journal Cancer Research that used MRI data from patients with TNBC to develop models to achieve early predictions of the tumor response of these patients.
“We calibrated our biology-based, mathematical model to make predictions of how tumors grow in space and time,” Yankeelov said. “They are highly accurate when predicting the response of TNBC patients to standard chemotherapy.”
Improved predictions provide physicians with information on whether a particular treatment course is likely to work.
Going forward, Yankeelov’s goal is to use mathematical modeling to identify an optimal intervention strategy.
“We use the mathematical model to build a ‘digital twin’ to try a myriad of treatment schedules to identify the one with the highest probability of success,” he said. “That is where the field is going.”
Yankeelov’s lab used TACC’s supercomputers to develop the digital twin. It was a fast turnaround—the digital twin sent patient data to help a physician with treatment decisions within 24 hours.
“Over the last eight years, TACC has provided extensive computational support for our research efforts via Lonestar5, Lonestar6, and Frontera,” Yankeelov said. “TACC has been there every step of the way as we develop methods for improving the treatment of—and outcomes for— patients battling cancer.”
HER2+ and Combined Therapies
HER2+ breast cancer overexpresses the gene that makes the HER2 protein—it is an aggressive cancer that responds well to treatments such as Trastuzumab (a monoclonal antibody), which is administered in combination with Doxorubicin (a chemotherapy drug). The challenge is optimizing the combination of these two drugs to maximize their efficacy.
Along with Yankeelov, Ernesto Lima co-authored a 2022 study published in Computational Methods in Applied Mechanics and Engineering. It developed a family of models to capture the effects of a combination of Trastuzumab and Doxorubicin on tumor growth to optimize the treatment outcome while minimizing the dosage and side-effects necessary to achieve tumor control.
“We created 10 models and calibrated them using the experimental data,” Lima said. Calibration involves adjusting the proliferation rate, which dictates how fast the tumor volume increases to align the model’s output with the experimental data.
Lima was awarded allocations through The University of Texas System Research Cyberinfrastructure on TACC’s Lonestar6 system to calibrate the models.
When parallelized, these comuputations ran 13 times faster. Parallelization divides large calculations into smaller ones that run simultaneously versus running the calculations one at a time.
“Using our model, we determined the optimal order and timing of drug delivery to maximize treatment efficacy,” Lima said. “One treatment protocol, with the same drug amount as in the experiments, achieved a 45 percent reduction in tumor size compared to the experimental controls.”
“Without TACC, our ability to explore treatment options and solve complex mathematical models driving forward our understanding of tumor biology would be significantly hindered.”
Biopsy Data Gold Mine
UT Austin has gained a gold mine of anonymized breast cancer data and tissue samples of other carcinomas, thanks to a donation from James L. Wittliff and his wife and collaborator, Mitzie, of the University of Louisville School of Medicine.
“This database and biorepository contains among the most highly quantified datasets of breast cancer biomarkers in the world.”
“This database and biorepository contains among the most highly quantified datasets of breast cancer biomarkers in the world, with several of the assays such as those for estrogen and progestin receptor proteins representing gold standard breast cancer tests,” said Wittliff, professor of biochemistry and molecular genetics.
More than 5,000 pristine breast, endometrial, ovarian, colon cancer biopsies, and nuclear pellets containing DNA were collected from patients and curated through a lifetime of research by the Wittliffs. They are now stored at the Dell Medical School at UT Austin. In addition, a treasure trove of comprehensive biomarker and clinical data is being exclusively stored and managed at TACC.
“Our immediate goal is to analyze these data in the context of the NIH’s Cancer Genome Atlas Program,” said Ari Kahn of TACC’s Life Sciences Computing Group.
The irreplaceable biopsies are now preserved for other scientists to use for clinical trials in silico and to develop future companion diagnostic tests.
“Wittliff is energized to expedite the use of the comprehensive data and unique samples to advance cancer diagnosis, treatment approaches, and ways to assess risk of recurrence of carcinomas. He is excited to support UT Austin, his alma mater, with this amazing gift,” Kahn added. “TACC is stewarding the data and plans to make it available to other scientists through a web portal.”
A Challenging Road Ahead
Cancer remains one of the biggest health challenges facing society. TACC offers scientists the computational resources needed to make discoveries that are effective for breast cancer patients. Rising survival rates over the past decade offer a glimmer of hope, thanks to awareness campaigns and increased funding for research.