Pioneering science at UCLA Health has changed breast cancer treatment worldwide
Long before Dennis Slamon, MD, PhD, was universally recognized for scientific discoveries that changed the trajectory of breast cancer and improved health outcomes for countless people across the globe, he just wanted to look at cancer differently.
“We were very much interested in the idea of translational cancer research,” says Dr. Slamon, director of clinical/translational research and chief of the division of hematology/oncology at UCLA Health. “Taking the knowledge coming out of basic science and applying it, where appropriate, to new approaches to clinical medicine and new therapies.”
When Dr. Slamon first came to UCLA as a fellow in 1979, cancer treatment was determined by the organ it affected, he says. All lung cancers were considered one disease and treated the same way; same with breast cancer or colon cancer.
“We should have realized back then that we were dealing with a diversity of diseases within that organ system, a diversity of cancers,” Dr. Slamon says. “Breast cancer was among the most obvious of those diseases where the outcomes were so varied, with some patients doing well and other patients doing poorly given the same approach to surgery, radiation and some chemotherapy or hormonal therapy.”
Dr. Slamon and his colleagues began searching for molecular-level malfunctions in cancer cells with the intention of developing more targeted treatments. This work not only led to major discoveries that have transformed breast cancer treatment, but influenced how cancer research is done.
In the 1980s, Dr. Slamon found a mutation in the HER2 gene common to a very aggressive form of breast cancer. This research and subsequent clinical trials led by UCLA resulted in the development of a drug called Herceptin, now the standard treatment for HER2-positive breast cancer, which accounts for about 20% of cases.
“Herceptin has altered the natural history of that subtype of disease, turning it from a bad-prognosis type of breast cancer to one that actually has a better prognosis than the other subtypes,” says Sara Hurvitz, MD, medical director of the Jonsson Comprehensive Cancer Center Clinical Research Unit and a colleague of Dr. Slamon.
Searching for molecular malfunctions
That turnaround in prognoses resulting from gene-targeted therapy inspired other oncology researchers to look for similar molecular malfunctions in the diseases they study, leading to a number of new, targeted treatments.
“In all these diseases there’s some diversity — colorectal cancer, lung cancer — and this is likely due to their molecular diversity, there are ‘many roads to Rome.’ There are a lot of ways to convert a normal breast cell or lung cell or colon cell to a cancer cell from that organ,” Dr. Slamon says.
“Whenever possible, therapy should be designed specifically to address what’s broken, as opposed to the non-specific bombs thrown in hoping to kill more bad cells than good,” he said.
Another discovery made by Dr. Slamon and colleagues has changed the trajectory for the most common type of breast cancer. Researchers at UCLA Health developed and led clinical trials for a targeted treatment for estrogen-receptor positive, HER2-negative breast cancer, which accounts for 65% of diagnoses.
The resulting medications, called CDK4/6 inhibitors (Ibrance, Kisquali and Verzenio), have been shown to improve progression-free survival from the disease, and now data is emerging showing this class of drugs extends patients’ lives, Dr. Hurvitz says.
“It’s ended up having the biggest impact in that sub-population of breast cancer since the introduction of hormonal therapy back in the 1970s,” Dr. Slamon says. “Both of those discoveries (Herceptin and CDK4/6 inhibitors) were game changers for the treatment of breast cancer now adopted worldwide. And those came from UCLA.”
Decades of advancement in research and treatment
UCLA Health has been a hub for breast cancer advances since the 1980s, with consistent discoveries over the decades, Dr. Hurvitz says. In just the past two years, four new breast cancer treatments tested at UCLA earned approvals from the U.S. Food and Drug Administration and more than 20 clinical trials are ongoing.
The average risk of a woman in the United States developing breast cancer in her lifetime is 13%, or 1 in 8, according to the American Cancer Society. For men, the lifetime risk is 1 in 833. About 281,550 new cases of invasive breast cancer are expected to be diagnosed in 2021. There are more than 3.8 million breast cancer survivors living in the U.S.
Though UCLA Health is a multidisciplinary system with breadth beyond cancer, its advances in research and treatment for people with cancer stands alongside those generated by cancer-specific centers, says Dr. Hurvitz.
“Even though we’re not a stand-alone cancer center, where that’s all we do, we have the ability to test drugs and concepts pre-clinically in the laboratory, design and run clinical trials, take the information as well as tumor tissue obtained from patients enrolled in those trials and test more new theories in the laboratory generated from the results of the trial,” she says. “So there's this cycle of translating discoveries from the lab to the clinic and back from the clinic to the lab.”
These advancements mean the outlook for breast cancer has improved significantly, Dr. Hurvitz says. It used to be that when she told people she was an oncologist, they’d get a “look of gloom on their face, like, ‘I’m so sorry for you.’”
“Because of discoveries and treatments we have now due to clinical research that was done in the last several decades, breast oncology is a much, much happier field in which to be a specialist,” she says. “To be able to dedicate time to research gives me a sense of hope, and deep satisfaction when our research actually translates into meaningful benefits for patients.”
Timeline: Breast cancer advances at UCLA Health
1987: Dr. Dennis Slamon and colleagues identify a link between a mutation in the HER2-positive gene and aggressive breast cancer.
1990: First human clinical trials begin at UCLA with the drug trastuzumab, which targets the HER2-positive gene mutation. Twenty women participate.
1998: The U.S. Food and Drug Administration approves trastuzumab, brand name Herceptin. It is the first approved treatment that attacks cancer at its genetic roots. The drug is now standard treatment for HER2-positive breast cancer.
2005: Dr. Slamon is the first to test a non-anthracycline chemotherapy treatment, previously the standard despite serious potential side effects, for curable breast cancer.
2013: Dr. Slamon and Dr. Richard Finn lead clinical trials of palbociclib, a groundbreaking treatment strategy to arrest tumor growth in people with estrogen receptor-positive advanced breast cancer.
2015: The FDA approves palbociclib as Ibrance, calling it a “breakthrough therapy” for this common form of breast cancer.
2019: Led by Dr. Slamon, UCLA Health researchers find that adding the targeted therapy drug ribociclib to standard hormone therapy significantly improves overall survival in postmenopausal women with advanced hormone receptor-positive/HER2-negative breast cancer, one of the most common forms of the disease.
2020: Based on clinical trials led by Dr. Sara Hurvitz, the FDA approves sacituzumab, commercially known as Trodelvy, to treat triple-negative breast cancer.
2021: The FDA grants “breakthrough therapy” designation to trastuzumab deruxtecan for HER2-postitive metastatic breast cancer based on trials led by Dr. Hurvitz at UCLA.
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