Debbie Davis was profoundly unlucky 28 years ago when she was diagnosed with breast cancer as a newlywed. Things got worse six years later when her cancer advanced to Stage 4. Her son was 4 years old.
But she's been incredibly lucky ever since.
As her tumor evaded one drug after another, new treatments kept coming.
Her remaining cancer cells are bombarded with chemotherapy from the pills she pops every day – but she still has all her hair, and she feels fine.
"Ninety-five percent of my life is the same as if I didn't have cancer right now," said Davis, 62, of St. Louis, who dedicates her free time to breast cancer advocacy. "It doesn't really ever go away. They can just stop it from growing."
Davis is an outlier because of her longevity with cancer, but she's getting more company.
As drug treatments improve, more people with breast cancer are living longer with a better quality of life.
"For many subtypes of breast cancer, while we still have a long way to go, we've made really quite dramatic and meaningful improvements," said Dr. Steven Isakoff, director of breast cancer clinical research at Massachusetts General Cancer Center in Boston.
Doctors are moving away from treating patients with high-dose chemotherapy to more targeted approaches, depending on characteristics of their tumors, said Ron Bose, Davis' doctor at Washington University School of Medicine in St. Louis.
Some of the progress, he said, has resulted from a deeper understanding of cancer biology – 50 years of hard scientific work, which began in 1971 with the declaration of the "War on Cancer."
Some of it can be credited to inexpensive genetic sequencing that provided insights into tumors and sped drug development.
And some comes from financial incentives driving drug companies to spend billions of dollars developing therapies, said Dr. Debasish Tripathy, chairman of the department of Breast Medical Oncology at the University of Texas MD Anderson Cancer Center in Houston.
"Our growing understanding of the fundamental nature of cancer, what drives it, what causes it – all of those things have come together," Tripathy said.
In the past few years – even in the past month – advances have come in all three major subtypes of breast cancer, Tripathy and others said.
New treatments enable people with early stage disease to avoid a recurrence and those with advanced cancer to stop counting their future in months.
"The challenge we have ahead of us is to best combine all of the methods that we have available," Isakoff said.
Here are the most significant recent developments by tumor type, according to a handful of breast cancer researchers who spoke with USA TODAY in advance of Breast Cancer Awareness Month, which starts Friday.
A protein called HER2 sits on the surface of many cells, telling them to grow more quickly and resist dying. In normal times, HER2 helps cells survive stress, said Dr. Ian Krop, a breast cancer specialist at the Dana-Farber Cancer Center in Boston. But in about 20% of breast cancers, there is too much of this protein, allowing the cells to grow aggressively.
In the early 1990s, the drug Herceptin from Genentech was developed to stick to cells and block the HER2 protein. Its success dramatically improved care for people with this type of tumor.
"Identification of what's driving a cancer leads to the ability to block that driver of the cancer, and that leads to progressively better outcomes," Krop said.
There are eight drugs that target HER2, four of which have been approved in the past 21 months, Krop said, and another is likely to be approved soon. Having so many options means that patients who don't do well on one can try another.
The new drugs, called antibody-drug conjugates, carry small payloads of chemotherapy directly to the HER2 tumor cells. This allows doctors to increase doses of toxic treatments, often without the horrible side effects usually associated with chemo. Krop described them as "guided missiles."
"Why give regular chemo that goes everywhere when you can hook it up to the antibody and take it where you want it to go?" Krop asked.
The first antibody-drug conjugate, called TDM1, was developed in 2012. The latest one, T-DXd or Enhertu was shown last month to triple how long a patient's advanced cancer stayed under control and more than doubled the percentage of patients who had substantial shrinkage of their tumors, Krop said.
The drugs are expensive but widely available and being tested in other tumors, including gastric cancers, he said.
"We are seeing patients do very well for very long periods of time with these drugs," he said. "If the cancer develops resistance to one them, it's very likely we'll have another that we can substitute that will get the cancer back under control, and we can keep doing that."
The next step, Tripathy said, will be to test these drugs in earlier-stage cancers, to see if they can prevent recurrences.
With so many effective drugs against HER2-positive tumors, Krop said it's time to start designing studies that look at whether advanced patients can actually be cured.
"Given we have all these effective drugs targeting HER2," he said, "can we start using them in particular regimens that become so effective that we can cure patients with metastatic disease – which has previously been unthinkable."
Estrogen receptor-positive tumors
About 65% of breast cancers are hormone-receptor-positive, HER2-negative tumors. Blocking estrogen in these patients can provide years of remission, Tripathy said.
Patients with advanced estrogen receptor-positive breast cancers that are inoperable, or have spread to other organs, are largely incurable despite treatment options.
Data presented last month showed that adding the drug Kisqali from Novartis extended postmenopausal patients' lives by more than a year over endocrine therapy alone.
More than half the patients survived at least five years past their diagnosis and some close to nine. "Not only did we improve survival, but we improved the quality of overall survival," said Jeff Legos, global head of oncology and hematology development for Novartis.
The drug, which normally adds few side effects, works by blocking enzymes called CDK4 and CDK6, stopping fast-growing cancer cells from replicating.
Dr. Cynthia Ma, a breast cancer oncologist at the Washington University School of Medicine, said her patients have gotten good long-term results from drugs that act on CDK4/6, and the drugs keep tumors under control longer than previous treatments.
"Our patient outcomes are so much better," she said. "They can do well for two to three years without having to change their treatment regimen."
Triple negative tumors
Some tumors have neither estrogen nor HER2. Until recently, these were the hardest to treat with the worst prognosis. "This was a cancer that was defined not by something it has but by what it lacks," Isakoff said.
Cancer immune therapies and a few other drugs have begun to change the landscape for triple negative cancers. "In just the last few years, we've seen some really major advances in the tools we have available to treat patients with triple negative breast cancer, both in advanced setting and in the early stage setting," he said.
A drug from Gilead called Trodelvy, approved in April 2021, used on patients with advanced cancer who have already tried at least two chemotherapy drugs, extends survival by more than a year. It is an antibody-drug conjugate, which means it targets cancer cells and delivers chemotherapy directly to the tumor cells.
"That drug has blown past what we had accepted as overall survival for triple negative breast cancer and has dramatically improved it," said Isakoff, who specializes in treating triple negative breast cancers. "That's been a real game changer."
Trodelvy is being studied earlier in the course of disease, while similar treatments under development aim at the same targets but with different, potentially more effective chemotherapy drugs, Isakoff said. "This has really opened up a whole new avenue of research that we're all very excited about."
Immunotherapy shows tremendous promise against triple negative breast cancer in combination with chemotherapy.
As the chemo kills cancer cells, the immune system – which had seen the cancer cells as the body's own cells and didn't attack – begins to recognize them as abnormal. "So the immune system now can kill cells that are your own body's cells," said Dr. Larry Norton, medical director of the Evelyn H. Lauder Breast Center at Memorial Sloan Kettering Cancer Center in New York. "That combination has made an enormous difference" in some patients.
One immunotherapy, Tecentriq, by Genentech, failed to show substantial benefit in triple negative patients. Another drug, Keytruda, from Merck, was shown to reduce recurrence for high-risk patients early in their disease. It's too early to know whether it will extend survival.
"As we unravel more as to how immunotherapy works, what types of tumors it works for better than others, what are the mechanisms of resistance, I'm pretty confident we're going to be developing more and more immunotherapies that are given in combinations to work better," Tripathy said.
Keytruda is given along with chemotherapy for six months before breast surgery, then alone for six months, he said.
It may be effective if given for less time, but studies have tried it for only that duration, Isakoff said.
"Overnight, that's become a standard of care for high-risk triple negative breast cancer," he said.
BRCA gene mutations
Drugs called PARP inhibitors have been shown effective for people with all breast cancer subtypes who carry genetic mutations on the BRCA1 or BRCA2 gene.
Normally, these genes correct mistakes as DNA makes copies of itself. In people with mutations in BRCA1 and BRCA2, the error-correcting system doesn't work well, allowing genetic mistakes to accumulate and tumors to begin.
PARP inhibitors actually add to the mutations. "If you damage the PARP process with an inhibitor, the cell has no means of repairing DNA," Norton said. The body notices the damage and triggers the cell's self-destruction mechanism.
For people with this genetic mutation, PARP inhibitors are even more effective than chemotherapy, he said. "That's a very exciting new approach."
Although most oncologists have been wary of declaring a cure for cancer, Norton said he thinks it's "an extremely feasible goal" to cure someone of breast cancer, if the definition of cure is "a resumption of normal life" for a normal lifespan. In other words, to keep them alive long enough to die from something else.
Davis, the patient in St. Louis whose tumor is HER2-positive, seems to be living out that promise.
She knows that her treatment will stop working, but she's optimistic that the rapid pace of drug development will probably provide another option when she needs it.
Davis often counsels patients early in their disease process, to offer them hope they'll get the kind of result she has enjoyed. It's gotten easier to provide that hope.
"It's more and more likely that they will do fine," she said, "because of all the recent and upcoming medicine in the pipeline."
Contact Karen Weintraub at firstname.lastname@example.org.
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This article originally appeared on USA TODAY: Breast Cancer Awareness Month: Recent treatment advances