Winning the War Against Breast Cancer: One Battle at a Time
By Michael Seringer
Breast cancer is not one disease, but many.
“Today we understand that breast cancer is definitely not one disease, but breast cancer is not three or four diseases, either,” said Virginia G. Kaklamani, MD, DSc, well-known physician-scientist and chair of Breast Cancer Research at the Mays Cancer Center, home to UT Health San Antonio MD Anderson Cancer Center. “It’s probably 10 to 12 different diseases, and by looking at the gene makeup of these specific breast cancers we are able to use targeted therapies that individualize treatment.”
Many drugs are discarded that may help one type of breast cancer, but not the majority. Defining the weaknesses of each type of breast cancer and then targeting those specific weaknesses is crucial to finding new treatments for this cancer. Investigators at UT Health San Antonio are finding that these newly discovered weaknesses specific to distinct forms of breast cancer can be targeted using repurposed drugs. These are drugs that are used for other diseases but have either never been tested in breast cancer or been tested and rejected, because the majority of breast cancer types did not respond.
For example, Dr. Kaklamani and Kimi Kong, PhD, associate professor of medicine, have found that drugs currently used to prevent rejection of transplanted organs can target inherited breast cancer, which represents only about 5 percent of all breast cancer. They have started a clinical trial testing this new therapy in this type of breast cancer.
David Gius, MD, PhD, assistant dean for research, has found another. “Women with a breast cancer type termed luminal B that have failed therapy have no hope,” he said. “However, these cancers require superoxide dismutase, which can be targeted by a drug used to treat other diseases.”
Such therapies targeted to the distinct forms of breast cancer are the future of breast cancer treatment, Dr. Kaklamani believes. Each of these forms of breast cancer arose from distinct mechanisms, so it seems obvious that they would need distinct therapies. Yet this concept is a recent development, although it has its roots in the breast cancer research team at UT Health San Antonio.
Individualizing Breast Cancer Treatment
This concept that distinct types of breast cancer require distinct therapies was built on work pioneered by William L. McGuire, MD, and many others who helped target cancer treatment to the individual patient. New targeting discoveries will provide clinicians with even more customized treatment plans and improved outcomes. Researchers with the Joe R. and Teresa Lozano Long School of Medicine are interested in the genetic evolution of tumors. They plan on matching interventions to the tumor’s change in order to improve treatment options. This research is just one example of personalized medicine designed to better target treatment.
A headline in The New York Times once heralded UT Health San Antonio’s work in measuring progesterone receptors as a “clue to breast cancer odds.” In reality, Dr. McGuire, pioneering breast cancer researcher and the first chief of oncology at UT Health San Antonio, was on to something much more radical. Dr. McGuire’s research took significant steps in targeting hormonal therapies to individual patients who expressed the estrogen and progesterone receptors—an idea that would come to define breast cancer treatment, improving the odds for everyone. This was the first example of individualizing therapy for each patient.
Dr. McGuire’s energy and attention to quality clinical trial design allowed him to quickly confirm the consequential role estrogen receptors play in predicting outcomes, a landmark research discovery made by Elwood Jensen, PhD. Dr. McGuire quickly recruited a cohort of more than 100 breast cancer patients in San Antonio. His research ultimately proved Dr. Jensen’s basic science, improved breast cancer treatment and distinguished UT Health San Antonio as a leading center in breast cancer research.
San Antonio—Synonymous with Breast Cancer Research
In 1978, Dr. McGuire and Charles Coltman Jr., MD, medical director of the Cancer Therapy & Research Center (now UT Health’s Mays Cancer Center), organized a small group of oncologists for a one-day meeting at a local hotel. Propelled by Dr. Coltman’s and Dr. McGuire’s determined leadership, this gathering of physicians was the first meeting of what is now the largest, most significant breast cancer symposium in the world, the San Antonio Breast Cancer Symposium.
The opportunity to be involved with the San Antonio Breast Cancer Symposium was one of the reasons Dr. Kaklamani decided to come to UT Health San Antonio from Northwestern University.
“It is the largest breast cancer symposium in the world. We have over 8,000 attendees coming from all over, every year,” said Dr. Kaklamani, professor of medicine in the Division of Hematology/Oncology at UT Health San Antonio. “All of the new research in breast cancer comes through this symposium.”
Decades after its founding, the symposium continues to bring together basic and clinical research, with the goal of accelerating both. Dr. McGuire foresaw the benefit of getting researchers in both the clinic and the lab to understand what each group was doing. It was translational research in practice before the term became popular. The symposium’s spirit of collegiality and collaboration was an extension of the culture being built at UT Health San Antonio.
Patrick Sung, DPhil, world-acclaimed biochemist and associate dean for research for the Long School of Medicine at UT Health San Antonio, believes the institution has a long trajectory of future growth because of its cooperative culture. Dr. Sung received the prestigious National Cancer Institute Outstanding Investigator Award and Recruitment of Established Investigators Award from the Cancer Prevention and Research Institute of Texas in 2019 and fosters a collaborative ethic in his lab.
“Culture is key,” said Dr. Sung, the Robert A. Welch Distinguished Chair in Chemistry and co-leader of Cancer Development and Progression at the Mays Cancer Center. “For a place to rise and be productive, it must be collegial and collaborative. Now, my best collaborators are in the same building.”
The culture at UT Health San Antonio is a selling point when recruiting researchers and patients, said Dr. Gius, associate director for translational research at the Mays Cancer Center, and a recipient of the Recruitment of Established Investigators Award from the Cancer Prevention and Research Institute of Texas.
“UT Health San Antonio has a long history of being a cooperative and collaborative institution where investigators really do want to work together,” he said. “That makes it fun.”
Dr. McGuire’s rule to never create obstacles between basic and clinical research is still followed at UT Health San Antonio and helps to foster a close working relationship between the lab and the clinic. Collaboration accelerates discovery, resulting in the ability of breast cancer patients to access more sophisticated, targeted therapeutic options more quickly.
The Next Ten Years
Dr. Sung believes the next decade will yield major discoveries in cancer research. His lab focuses on DNA repair mechanisms, a better understanding of which may yield more effective treatments. His lab hopes to identify new targets and develop precise genomic therapies.
“Research into the repair of these DNA double-strand breaks will give us a better understanding of how to manipulate the pathway for therapeutic gains,” Dr. Sung said. “This could be applicable across tumors and would help with drug resistance by shutting down the tumor’s ability to repair itself.”
“As you look at the next ten years what we are going to be seeing is a lot more targeted approaches based on the genomic makeup of the tumor and that genomic makeup actually changes over time,” Dr. Kaklamani said. “Instead of just looking at one time point, we are going to be looking at different time points and adjusting our treatments over time to fit how the cancer is evolving.”
Dr. Kaklamani believes there is much work to be done in the early detection and prevention of breast cancer. She said community efforts must engage underserved patients and health care providers must promote breast cancer screenings to the broader community. Early detection reduces health care inequalities, she noted.
“Around 60 percent of our patients are Hispanic, and about 60 percent of this population is underserved, and this comes with its own challenges. We know from many, many studies that patients that have a low socioeconomic status have worse outcomes,” Dr. Kaklamani said.
Along with reaching out to underserved communities to address inequalities in breast cancer treatment, UT Health San Antonio is promoting prevention through early detection. Educating women on preventing breast cancer is key to reducing health inequality and saving lives.
An effective prevention plan starts with identifying individuals who have a high risk for breast cancer, Dr. Kaklamani said. Once they know their breast cancer risk, patients can make more informed decisions regarding preventative therapies.
Investments made in UT Health San Antonio’s cancer genetics program help identify women at high risk. Genetic counselors then educate patients and provide personalized prevention strategies. This program reduces costs by preventing much more expensive treatment options required when breast cancer is detected later, Dr. Kaklamani said.
This approach is improving patients’ odds of surviving breast cancer. It is just one of many efforts at UT Health San Antonio that brings together basic science and clinical research to propel discovery—a fitting legacy to Dr. William L. McGuire.