City of Hope has lived up to its name for breast cancer patient Linda Collins. When the Hemet resident visited Duarte’s comprehensive cancer center for a second opinion, she had no idea that she was literally saving — or at least extending — her own life. “The treatment my regular oncologist planned for me would have been totally ineffective and useless,” she says. “It might even have killed me.”
Collins, 57, arrived at City of Hope a little over a year ago with a diagnosis of stage 4 metastatic triple-negative breast cancer and a prognosis of about one year to live. She met with oncologist Yuan Yuan, M.D., Ph.D., who took over her care and then designed a clinical trial for women with triple-negative status, one of the most difficult types of breast cancer to treat. After a year of treatment with Yuan’s innovative combination of drugs, Collins has become what City of Hope calls “the first success story” for women with her type of disease. Instead of feeling like she’s at death’s door, she says she feels good. Her cancer is now almost undetectable.
“I still can’t believe it,” Collins says. “I haven’t quite absorbed it yet. It’s just too wonderful and I feel very humble.” But she’s also realistic. “There is no cure yet for metastatic breast cancer, which is what I have,” she adds. “Dr. Yuan has explained it all to me. She’s amazing.”
In 2011, Collins was diagnosed with an aggressive form of breast cancer and underwent chemotherapy, surgery and radiation. “The chemo was very strong for this type of cancer,” and it was devastating, Collins says. Her hair, eyelashes and nails fell out, she lost 60 pounds and she felt sick much of the time. But the chemo worked. She remained cancer-free for the next five years, after which she had to start with a new oncologist due to a change in her insurance plan.
“He continued to monitor me with mammograms and blood tests, and all tests came back clear,” she recalls. She was just beginning to relax and enjoy her cancer-free status when she detected pain in her lower back. Her oncologist kept saying it had nothing to do with cancer, because all his tests proved she was okay. But the pain persisted — and so did she. “He was about to send me home yet again because my blood tests and mammogram were still clear. But I told him, ‘You say I’m okay, but I don’t feel okay. I need you to do something.’ So he finally ordered a scan.”
The scan showed she had three masses in her chest, which were then biopsied. “It was breast cancer that had metastasized and spread,” Collins says. Her oncologist set her up with a treatment plan that consisted of the same kind of chemotherapy she’d had before. She was terrified to go through that again, but saw no options. Then her niece, a physician’s assistant, urged her to get a second opinion at City of Hope, where, the niece said, all sorts of new targeted therapies were being tried, some of which might not even require chemotherapy.
Once under Yuan’s care at City of Hope, Collins learned that the treatment her prior oncologist had prescribed for her was based on a false assumption: that her metastasized cancer was the same type of cancer she’d originally been treated for, which is called ER positive. If he’d done the needed tests, Collins says, he’d have found that her new cancer was a different type, called triple-negative. It would not have responded at all to the treatment he proposed.
But even had he done all the right tests and treatments, he probably still wouldn’t have been able to do much for her. Triple-negative breast cancer is a less common form of the disease, and there’s been little success treating it, says Yuan. “The prognosis is 12 to 18 months,” she notes.
We asked Yuan how she decided to create Collins’ clinical trial. “Breast cancer is such a common disease and affects so many people’s lives,” Yuan says. “Early stage breast cancer, thanks to all the previous research and medicines, is largely curable and treatable. But every day we face folks who come to us with so-called metastatic or noncurable disease. It has metastasized to elsewhere and creates a limited life span. So that’s where our passion is. We want to bring more novel treatment to help these women and one day cure them, just as nowadays we’re curing lymphoma and leukemia. But so far, we haven’t cured a lot of solid tumors.”
Is metastatic breast cancer considered a solid tumor?
“Yes, it can be melanoma, lung, brain, colon or other kinds of cancer. With metastatic cancer, the cancer is there, but it’s probably microscopic disease that we can’t diagnose” until it shows up as a solid tumor, Yuan says. In Collins’ case, she explains, extensive testing revealed not only the bad news — that her patient was triple-
negative for all three hormone receptors and therefore not a candidate for targeted therapy — but also a smidgen of possible good news: Collins tested positive for
androgen receptors, which are cells that respond to the male hormone.
There is a drug for prostate cancer in men that targets androgen, Yuan explains. That drug had already been tried in studies of triple-negative breast cancer patients like Collins, but with limited success. Yuan wanted to try it again, this time combined with state-of-the-art immunotherapy drugs that boost the patient’s immune system and had recently become available. “I applied to Merck, which got FDA approval for Keytruda in 2016, and we got Merck to sponsor this study which combines an androgen-receptor modulator with new immunotherapy.”
Collins was enrolled in the trial, along with a number of other women with the same cancer profile, but she was the one with what Yuan calls “the most durable result.” Of 15 patients currently in the trial, there have been four or five “responders,” Yuan says, meaning women who have benefited to some degree from the drugs.
Collins’ result has been the longest lasting and is “very positive, but it’s too soon to declare anything,” Yuan says. “We can say she has good cancer control with the current regimen, and she continues treatment.” And bear in mind, Yuan adds, that the regimen Collins is on is appropriate for only 10 percent of triple-negative breast cancer patients — those with androgen receptors. So this trial is for just a small subset of triple-negative cases.
For those who’ve wondered why, after all these decades of research, there’s still no cure for cancer, it becomes clear from talking to Yuan that cancer is not just one disease — it’s many different diseases, each of which has different subsets with characteristics that respond to different therapies.
Collins says she feels good while taking the medication recipe prescribed by Yuan. Unlike chemotherapy, the drugs have had few side effects, she says. She has a port implanted, and goes to City of Hope every three weeks for an infusion of Keytruda; she also takes six androgen-targeting pills each day at home.
Yuan says she currently has six or seven trials focused on metastatic breast cancer, using various immunotherapy drugs in conjunction with targeted therapy drugs. Innovation in treating breast cancer is generally moving away from chemotherapy, toward newer therapies that kill cancer cells specifically and have fewer side effects. Other research doctors at City of Hope are also conducting many such trials in a hunt for cures for numerous kinds of cancer. One of many she mentions is the prominent City of Hope professor and surgery department chairman, Dr. Yuman Fong, who is conducting “the very first human study using an attractive new tool called ‘oncolytic virus,’ also known as the virus that eats cancer.”
For those of us not familiar with medical lingo, we asked Yuan to explain targeted therapy. “There are many drivers that cause the cancer to continue growing. Cancer cells are unique, because they don’t know how to die. Some of the molecules are constantly turned on, or mutated or amplified. They’re constantly active. Targeted therapy is designed specifically to alter those particular cells, whereas chemotherapy is very broad. It kills healthy cells as well as cancer cells.
“Later on, those cancer cells learn how to become resistant to the chemotherapy, and they revive, so that will not be the answer. One of the target therapies we’re now using is immunotherapy, which can be pills or I.V. injections. But it’s not like conventional chemo; it doesn’t cause hair loss, nausea, etc.”
Yuan says the idea behind immunotherapy is that people without cancer have healthy immune systems that can detect cancer cells and kill them before they form a tumor. It’s all very complex to describe, she explains, but a number of immunotherapies are being tested that will help strengthen the immune system and prevent healthy cells from being hijacked by cancer cells. One therapy involves removing tumor cells, re-engineering them and returning them to the patient. “We put them in a petri dish, treat them to change the property of the cells, then infuse them back into the patient so they are able to function.”
Collins, who teaches art and music to elementary school children in Hemet, is the married mother of three grown children who’ve “been very helpful to me throughout my illness. One of my daughters really battled with my health insurance to get approval for me to go to City of Hope, which the insurance at first denied.”
We asked Yuan if patients and their insurance are required to pay for clinical trials, or if the trial host pays. “Nowadays, it’s a kind of hybrid model, because patient costs for a clinical trial are extremely high,” she says. “The most common model is that insurance pays for standard care, for example, doctor’s visits, standard blood draws and standard imaging, such as CTs and bone scans. The study pays for all the stuff that normally wouldn’t be standard care. That includes the study drugs, the study nursing time and all the specific biopsies, special imaging, special blood tests and other items that are required for the study but wouldn’t normally be done for standard care. For example, we collect stool samples for the study because there’s interesting data showing that our gut bacteria actually may determine if we are responding to immunotherapy or not. So we do a lot of types of special studies that patients do not pay for.”
Yuan is married to Kuo-Sheng Ma, Ph.D, a professor of electrical engineering and computer science at Loyola Marymount University. They live in South Pasadena and have two daughters, ages 6 and 9.
Does she think that within her lifetime there will be cures for metastatic breast cancers? Or if not cures, then therapies that will allow women to live relatively normal lives while keeping the cancer under control?
“Absolutely, I think so. There’s lots of hope. If you look back over the past few years, changes are incremental, but they are happening and there’s been lots of recent progress. It’s now a speeding train, and it will get faster and faster, with more new drugs all the time. Of course, if you have a friend who’s sick now and can’t get helped, it is so sad.” She sees that every day, she says, and that’s what the doctors at City of Hope are trying to change.