It has been a long journey, but a potential treatment for triple-negative breast cancer is working its way toward clinical trials much faster thanks to donors such as Ginny L. Clements, Dr. Joyce Schroeder’s laser-focused cheerleader.
by Anna C. Christensen and Gaius J. Augustus
In 1956, Ginny L. Clements was a 15-year-old pom-pom girl, and the word “cancer” wasn’t on her radar screen. So when she found a lump in her breast, she initially let it go.
“Who knows anything about cancer at 15? At 15, all you think about is your studies and boys,” she says with a laugh.
Nevertheless, she finally became concerned enough to approach her mother, who was a registered nurse.
“She went into action,” Ms. Clements recalls. “I visited a couple of doctors, who told my mother that I had breast cancer and needed immediate surgery. At that time, they not only took my breast but my breast muscle too. It was quite a shock, at 15, to wake up and have no breast and be so scared.”
The surgery turned her world upside down.
“As a young teenager, it was very traumatic to me, to say the least, because everyone knew my family and me,” Ms. Clements says. “We lived in the small farming community of Fowler, population 1,869, which is 10 miles south of Fresno in the San Joaquin Valley of California.”
She spent her junior year recovering, worrying about what the future might hold. By senior year, she was back on the field as a cheerleader. Soon after graduation and college, she launched her adulthood in San Francisco to discover what the future had in store for her.
A promising candidate
When Ms. Clements was diagnosed, breast cancers were treated surgically with radical mastectomy. Fortunately, medical science has made enormous progress in the ensuing decades, producing chemotherapies, targeted drugs and less invasive surgical procedures.
This progress is the result of work being done in laboratories across the world, where researchers churn out drug candidates for further investigation. Most of them never make it to clinical trials. A battery of testing is required to make sure an experimental drug will not be toxic to patients and can be mass produced, but equally important is understanding how the drug might work.
The job of basic scientists such as Joyce Schroeder, PhD, director of the UA Cancer Center Metastatic Breast Cancer Initiative and head of the Department of Molecular and Cellular Biology, is to dig into biological processes and figure out what makes cancer cells different from normal cells. Dr. Schroeder is leveraging that knowledge to develop a targeted drug that someday may help patients in the clinic.
“We need to understand what is driving cancer and what processes are specific to cancer,” Dr. Schroeder says. “If we don’t understand that, there is no way we can develop a useful therapy.”
Her hard work has paid off in the discovery of a compound that she hopes will make it through clinical trials, called SAH-EJ1, or EJ1 for short, which is being developed to treat triple-negative breast cancer. There are therapies that target the three known receptors present in most breast cancers. However, triple-negative breast cancer is notoriously difficult to treat because it lacks these three receptors. Finding a way to target it would be a huge boon for breast cancer patients.
An effective treatment needs to be specific to cancer cells so that normal cells will mostly be left alone. EJ1 targets a receptor called epidermal growth factor, which is highly expressed in triple-negative breast cancer — driving the growth of these breast cancers and making it an intriguing target for a drug. Not all cancer “drivers” can be targeted by a drug, but so far, blocking the function of epidermal growth factor receptor using EJ1 has shown promise.
Dr. Schroeder’s experiments have shown that EJ1 holds strong potential for treating triple-negative breast cancer, but is especially promising in treating inflammatory breast cancer, a rare form of the disease that can progress over the course of weeks or months.
“There’s no targeted treatment for inflammatory breast cancer,” Dr. Schroeder explains. “It’s a particularly aggressive subset of the disease.”
Experiments pitting EJ1 against inflammatory breast cancer provide early evidence that the drug could be effective in clearing both the cancer and the associated inflammation.
“It effectively treats inflammatory breast cancer in animal models,” says Dr. Schroeder. “Now, we’re trying to take it to human clinical trials.”
EJ1’s potential to treat some of the most challenging types of breast cancer is exciting, but moving it from the laboratory to the clinic is a long and expensive process. Before EJ1 can move into clinical trials, funding agencies must be convinced it is ready. Further tests include learning more about the drug’s toxicity profile as well as making sure it can be mass produced to meet market demand.
“Every single one of these steps requires a lot of money — and a lot of people willing to back you,” says Dr. Schroeder.
An invested philanthropist
Ms. Clements’ life in San Francisco unfolded in ways she never could have imagined back when she was 15 years old and recovering from a shocking surgery. It was there that she met a neighbor, Bill Clements, whom she married three months later. They soon moved to Phoenix, where their children were born, and in 1974 they moved to Tucson, where they grew their family business, Golden Eagle Distributors.
In 1972, she lost her best friend, Claudia, to breast cancer. She still gets tears in her eyes when she remembers her. Years later, in 1995, lung cancer claimed her husband’s life. She took over the family business, which prospered under her leadership, seeing record sales and expansion. When she retired in 2003 from the day-to-day business operations, she wondered how she could stay active and give back to her community. Memories of her experience as a teenager came back to her.
“I decided, on my 50th anniversary of being a breast cancer survivor, to establish a legacy to fund breast cancer research,” she recalls. “I wanted to honor and fight for those who weren’t as lucky as I have been, and for those who are survivors of this horrible cancer.”
Meanwhile, Dr. Schroeder was busy at work in her lab, hoping that one of her drug candidates would someday make it into the clinic. The studies necessary to get FDA approval for an early clinical trial can take a long time if funding is unavailable or limited. Private donors can expedite this research, making the road to clinical trials shorter.
“We were having difficulty getting government grants for drug development,” Dr. Schroeder recalls. “This is when people like Ginny L. Clements stepped in and made a huge impact — the science didn’t have to stop.”
Dr. Schroeder remembers receiving a call one day, more than a decade ago, notifying her that a prospective donor was in the building. “Ginny wants to talk to anybody who’s doing breast cancer research,” Dr. Schroeder was told. “She’s coming down to talk to you in 20 minutes.” The meeting changed the course of Dr. Schroeder’s work.
“Unlike most donors, she interviews her scientists,” says Dr. Schroeder. “She showed up in the lab, walked through, and we talked about what we’re doing and where we wanted to take our research. She started putting her money into our lab. She’s been absolutely phenomenal.”
“I don’t want to give money and not know where it’s going. That’s not my style,” says Ms. Clements of her collaborative approach. “I’m so happy that I have the means to do this. I’m very blessed.”
Dr. Schroeder was immediately impressed by Ms. Clements, whose dedication to finding a cure has never wavered.
“She is 100 percent laser-focused on curing breast cancer,” Dr. Schroeder says.
That focus took decades to develop. Between the time of her diagnosis in 1956 and the formation of the Ginny L. Clements Breast Cancer Research Fund at the University of Arizona Cancer Center in 2006, Ms. Clements never discussed her early battle with breast cancer publicly. She credits the burgeoning awareness movement surrounding breast cancer with shifting her outlook.
“I made a decision to openly change how I felt about my experience with breast cancer,” she recalls. “Before it was a pretty hush-hush subject. I felt that I needed to speak out and be more transparent.”
Ms. Clements also makes it clear why breast cancer research is a priority for her.
“I’m doing this for those who have lost their lives — especially for Claudia,” Ms. Clements says of her philanthropy. “When people die who are close to you, you really want to fight.”
Though she put her pom-poms down decades ago, Ms. Clements still knows how to energize a crowd, and along with other donors is a source of inspiration for Dr. Schroeder.
“They’re like a cheerleading section,” Dr. Schroeder says of the philanthropists who make her research possible. “A lot of times you’re working hard and having a variety of roadblocks. Staying optimistic can be difficult during those times, but my donors always email me, call me, send a letter saying, ‘We were thinking about you. Thank you for all that you’re doing to cure this disease.’”
Ms. Clements is hopeful that Dr. Schroeder’s research will be successful.
“I think Joyce has been on the right road,” says Ms. Clements. “But at times, we have been struck with disappointing reports, which has brought tears to my eyes, wondering if we are ever going to make it happen. Research is fickle. Sometimes you hit it out of the ballpark, and sometimes you don’t. I sincerely think EJ1 is so promising, and I feel I will see the fruits of my labor and Joyce’s labor down the way.”
An exciting journey
After years of success as a laboratory scientist, Dr. Schroeder now looks forward to moving her targeted therapy from the lab to the clinic, but first she needs to complete FDA applications and more rigorous testing.
“There was a lot about the clinical trials process that I didn’t know about,” says Dr. Schroeder. “The largest difference between a clinical trial and basic research is that it’s going to happen in a human being.”
Taking her research from the laboratory into a human body is an undertaking that Dr. Schroeder regards with great respect.
“Moving from the lab to patients raises a lot of concerns, because you would never want to harm a patient,” says Dr. Schroeder. “You’re already going through your data to make sure it’s as accurate as possible, but when you have that additional emotional concern, it really makes you sit back and re-evaluate everything.”
All the effort is well worth it, as EJ1 is inspiring optimism and progress is being made to advance to a phase I clinical trial.
“I have the utmost faith that I am making a difference, and with Joyce’s continued research, together, we will eradicate breast cancer in women and men in our lifetime,” Ms. Clements says.
It has already been a long journey, but a potential treatment for triple-negative breast cancer is working its way toward clinical trials much faster thanks to donors such as Ms. Clements, Dr. Schroeder’s laser-focused cheerleader.
Photo 1: Ginny L. Clements and Joyce Schroeder, PhD (photo: Kris Hanning)
Photo 2: The Schroeder Lab is powered in part by students, including undergrads Alexa Nguyen (left) and Vito Marino. (photo: Kris Hanning)
Photo 3: Ginny L. Clements (left) and Joyce Schroeder, PhD (photo: Kris Hanning)