Some clinical trials for new approaches to treating breast cancer involve small groups of patients and limited time. Others are nationwide studies involving thousands of volunteers whose cancer is tracked for years at numerous partner institutions. Meanwhile, laboratory scientists are developing new compounds with surprising anti-cancer properties.
“This is exciting,” said Dr. Michael Cohen, an associate professor of chemical physiology and biochemistry at the Oregon Health & Science University School of Medicine in Portland. His lab is working on what he hopes will be a new generation of drugs that fight many kinds of aggressive cancer, including breast cancer.
“It’s a generation in the future, but we may be able to help a pretty significant number of people,” Cohen said.
Treating breast cancer is “a very dynamic field. There’s always something new,” said Dr. Cory Donovan, a surgeon and researcher at Legacy Salmon Creek in Vancouver. “I’m continually impressed by the bravery of my patients and colleagues, to take these leaps, to try new things. That benefits everyone.”
How much is too much?
Donovan is passionate about determining just how little intervention her patients really need, she said.
“We want to figure out the right amount of treatment for each of our patients,” she said. “Crucially, we want to be asking the question, ‘Are we doing too much?’ ”
In the late 1800s, she said, the standard of care was highly invasive — total mastectomy. While that raised the cure rate from zero to 50 percent, it was also “a disfiguring, disforming and burdensome operation that maimed women,” Donovan said.
In the 1970s, she said, patients started questioning whether such radical intervention was always necessary, and doctors started searching for more careful, cautious approaches. These days, Donovan said, she’s especially excited about recent and ongoing clinical trials aimed at avoiding too much treatment.
“The vast majority of early-stage breast cancer patients will be alive in 20, 30, 40 years,” she said. “What will the consequences of therapy be for their future selves?”
As a cancer survivor who underwent bilateral mastectomy, chemotherapy and radiation, Donovan said she takes these matters personally.
Those procedures “saved my life and I’m so thankful for them and for modern medicine,” she said. “But if there are women who don’t need all that, who are they? Can we spare them?”
After a lump is removed, biopsied and determined to be pre-cancerous (“sleepy, slow-moving, stage zero,” Donovan said), is it better to go back and perform a partial or full mastectomy — and follow that with radiation therapy — or simply wait and watch? In a big trial named COMET (for Comparison of Operative versus Monitoring and Endocrine Therapy), Donovan said, about 1,000 breast cancer patients were randomly assigned to different treatment groups (without knowing which treatment they’d get). Some underwent surgery, followed by radiation; others were simply monitored closely. All were offered estrogen therapy.
“Are there specific patients with pre-cancers who are being overtreated?” Donovan said. “A large number might benefit from invasive surgery, but are there patients who won’t benefit from that? Who are they? Would they benefit more simply by taking a pill and watching?”
Donovan said a few of her own patients, who were “randomized” into the pill-and-watch group two years ago, have not seen their pre-cancer progress at all.
“What’s the benefit of radiation for women with early stage, very tiny, very sleepy estrogen-receptor-positive cancers?” Donovan said.
Post-lumpectomy, she said, “some women will get the traditional treatment that’s the standard of care, which is going for radiation to the whole breast, five days a week for five weeks.” Another group won’t get any radiation at all, just active monitoring, she said.
“With patients who have these small, slow, sleepy cancers, can we do less?” she said.
Similar science has already allowed some women to opt out of post-surgery chemotherapy and potential side effects like pain, fatigue and hair loss, she said. This trial may get closer to the same for radiation therapy, which shares many of those nasty side effects.
“Surgeons are always excited about new toys,” Donovan said.
A combination of new tools help accurately target and remove the least possible amount of flesh around a breast tumor while still avoiding the need for more surgeries.
First comes Savi Scout, which uses a tiny, implanted radar reflector to pinpoint the exact location of a tumor that’s too small to be felt or seen. It’s an improvement over the previous technology, which uses guide wires for the surgeon to follow to the tumor.
Those guide wires can be precarious, Donovan said. Savi Scout allows for greater surgical precision and the removal of less surrounding breast tissue.
Next, the tumor is analyzed — immediately, in the operating room — by an imaging machine Donovan called Mozart, more formally known as the MOZART iQ 3D Margin Management System. Mozart represents a leap forward, from flat X-rays to a 3D image presenting a fuller picture of what’s inside the tumor and just how close to its edge the surgeon’s knife must go to get it all, Donovan said.
Using Savi Scout and Mozart makes surgery more effective, avoids subsequent procedures and leaves patients looking cosmetically better too, Donovan said.
“Patients really don’t like going in a second time,” she said. “If I can decrease that risk for my patients, that makes us both happy.”
A small minority of breast cancer patients benefit from PARP-1 inhibitors, which prevent faulty cancer cells from repairing themselves and carrying on their fast-replication work.
PARP-1 inhibitors are “not as toxic as chemo and can be very effective against some pretty aggressive cancer types,” Donovan said.
PARP-1 inhibitors have mostly been deployed against ovarian cancer, but Oregon Health & Science University researcher Dr. Michael Cohen has developed what he calls a second-generation PARP-1 inhibitor that may prove more widely effective against different forms of invasive cancer — including tough-to-treat triple-negative breast cancer. (The name comes from the fact the cancer cells don’t have estrogen or progesterone receptors and don’t make a protein called HER2.) This type of cancer is not only more aggressive, it also has a higher risk of metastasizing and recurring.
“First generation PARP inhibitors don’t do anything against triple-negative cancer,” Cohen said. “Our compounds are quite effective against triple-negative cancer cell lines.”