The new ways to beat breast cancer

Lisa Fitterman

Trials of non-invasive, painless treatments to beat this disease are showing excellent results.

"It sounded exciting, like science fiction"

breast cancer

On a cold January day in 2011, Margareta Nordell bundled up in her winter coat, hugged her dog Jackie goodbye and went off to have a mammogram—just as she had every 24 months for the past 20 years. A customer representative for a Stockholm insurance company (now retired), she wasn’t worried.

Never before had a suspicious lump or shadow been found and she assumed this time would be no different. She was wrong. When the X-rays were processed, her doctor pointed to a dot on her right breast. It looked like a speck of dust or something smaller, even.

“But I can’t feel it when I check,” Margareta protested.

“That’s a good thing,” her doctor replied. “If it’s cancer, we’ve probably caught it in time, before it grows into something you can feel.”

A biopsy proved it was malignant. All of a sudden Margareta, then 66, an independent mother and grandmother, found herself thrust into a vast club she would much rather not be part of: women with breast cancer. An estimated one in every eight women around the world will develop the disease in their lifetime.

 

 

Margareta Nordell was fortunate to take part in a trial of a new therapy

 

 

Margareta didn’t even consider a lumpectomy: early in the treatment, her doctor asked if she would like to be part of a local trial into a procedure called “preferential radio frequency ablation”, or PRFA, which is based on the principle that cancer cells can be killed by heating them up. Her age—and the tiny size of the tumour—fitted the trial’s criteria; while there was no guarantee it would work, there would be no cutting into her breast and zero recovery time. She would be given a local anesthetic and the whole thing would last about 20 minutes. 

It sounded exciting, like science fiction. Margareta would still undergo minor surgery to remove the dead tissue a few weeks after having the procedure so scientists could examine it, have radiation to ensure the cancer was gone for good and be prescribed a drug called tamoxifen to prevent it recurring. But she knew she would be helping women diagnosed in the future perhaps avoid the operating table altogether.

“Absolutely, I’ll do it,” she said.

Read more: Getting the better of breast cancer

 

A pioneering treatment

PRFA is one of a number of new breast-cancer treatments being tested on patients right now.

They represent a radical departure from the standard “one size fits all” medical approach: cut off a whole breast or at least excise part of it, then radiate, then, if the tumour was really aggressive, use chemotherapy—making the overall treatment a trifecta for side effects like nausea, hair loss and brain fog.

As recently as 50 years ago, scientists thought most tumours were alike and there were few treatment options outside of surgery, radiotherapy and chemotherapy. Around one in four people survived cancer, compared to half today. In the 1970s, in the first glimmer of exciting changes to come, doctors began to test new treatments such as the “precision” drug trastuzumab, a laboratory-produced antibody treatment better known by its brand name Herceptin, which can stop cancer cells from growing.

Thanks to advances in genetic testing, we now know even more about breast cancer. A landmark 2012 study undertaken by scientists at Cancer Research UK’s Cambridge Institute, for example, proved that the disease can be divided into ten different sub-groups, each of which may respond to different combinations of drugs, non-invasive treatments, surgery or, in the case of tumours that grow really slowly, no treatment at all.

We know about gene mutations, both acquired and inherited, and the possible effects of hormonal levels and smoking on cancer. At this stage, there’s also evidence that alcohol consumption, excess weight and a lack of exercise increases this risk of developing breast cancer.

 

Alcohol consumption, excess weight and a lack of exercise all increase the risk of breast cancer

 

 

“We’re continuing to develop methods to detect tumours earlier, and to find new telltale markers in order to help doctors better tailor treatment,” says Dr Áine McCarthy, the organisation’s senior science information officer. When doctors know what they’re dealing with, be it an ER positive tumour (which grows in response to female hormones) or a HER2 positive tumour (one which has large amounts of the human epidermal growth factor receptor 2 protein on the surface of the cancer cells) it makes all the difference in helping doctors develop a treatment plan.]

Even more recently, an international study published last spring in Nature examined in detail the genomes in 560 breast cancers, sifting through billions of letters of code to find the mutations in each case. This research, led by the Wellcome Trust Sanger Institute in Cambridge, isn’t a new cure, but it represents a leap towards treatment that’s tailored for each patient.

“All cancers are due to mutations that occur in all of us in the DNA of our cells during the course of our lifetimes,” said director of the Institute and professor Sir Mike Stratton. “This study brings us much closer to a complete description of the changes in DNA in breast cancer and thus to a comprehensive understanding of the causes of the disease and the opportunities for new treatments.”

 

Patient, heal thyself 

The immune system is a mysterious thing that can swoop in to heal your common cold and cause autoimmune conditions such as arthritis and type-I diabetes. Researchers such as Dr Pam Ohashi, director of the tumour immunotherapy programme at the Princess Margaret Cancer Centre in Toronto, are now trying to harness its power to combat breast cancer. The idea is to stimulate one’s own immune system to work harder and attack cancer cells.

“There are these molecules called ‘checkpoint inhibitors’, which act as stop signals and regulate the immune system,” explains Dr Ohashi. Clinical trials in certain types of cancer that naturally induce a strong immune response—such as melanoma—have tested drugs that block these negative signals, and the results have shown that releases the body’s T cells, the foot soldiers of the immune system, to go and fight tumours.

“We’re trying to see if the same principle works with breast cancer,” Dr Ohashi says. Patients in clinical trials are getting immune therapy as a last resort after proven treatments haven’t worked.

Once scientists have figured out how to make the immune system work better, immune therapy may be given to breast-cancer patients early on, thus allowing them to skip chemotherapy and/or radiation.

“Combined with other strategies, it has the potential to cure cancer,” says Dr Ohashi. “That could be ten years down the road, but the time has now come to think of it as a reality.”

 

Cooling things down

The idea is simple: cool a tumour and the surrounding tissue to the point that the cells within freeze, let the cells burst their cell boundaries or “pop” like a full can of frozen soft drink, and after the malignant ones rupture they’re harmlessly reabsorbed into the tissue. An Israeli invention, the IceSense3 machine, which requires a needle to be inserted into the breast tumour, is being tested in patient trials across 20 sites in the US and also in Japan, Europe and Hong Kong.

Already successful in kidney, liver and lung-cancer treatments, the procedure, which is limited to women aged 65 and over with breast tumours that are no more than one-and-a-half centimetres in diameter, takes up to a half an hour and requires only a local anesthetic. 

“You turn the machine on once the needle is placed and it gets cold in about 20 seconds,” says Will Irby, a vice-president at the Memphis-based IceCure Medical Inc. “The tumour is frozen from the inside out and you can watch the ice ball being formed with the help of an ultrasound.”

 

 

Having the procedure in February was “a piece of cake”

 

 

Dr Richard Fine, the director of education and research at Margaret West Comprehensive Breast Centre in Memphis, notes the procedure is non-surgical—and indeed its goal is to replace the surgical treatment of the breast cancer.

“The patient will still feel a lump for about six months, as the dead cells are being reabsorbed and the changes caused by the cryo-ablation are being resolved,” he says. “After that we do a mammogram where we can see normal breast tissue surrounded by a white outline, which surrounds the zone of treatment.”

For New Jersey resident Muriel Smith, having the procedure in February was “a piece of cake”—so easy, in fact, she hopped off the table at the medical centre, donned her shirt and went off to a lunch date. Diagnosed in December last year, she opted for cryo-ablation over surgery because the latter required so much more effort and someone would have had to pick her up afterwards.

“At my age, I’m not crazy about going under anesthesia,” says the 79-year-old. “I was able to watch every-thing on the screen. Forty-seven days after diagnosis, I was free of cancer.”

 

Heatings things up

For preferential radiofrequency ablation, or PRFA—the procedure Margareta Nordell had—the doctor first carefully guides a needle into the tumour with the help of an ultra-sound machine and then secures it in place using mechanical micropulses. Cancer cells trying to escape through the tumour’s blood vessels are quickly killed off by the electric pulses in a process called anti-seeding.

Once positioned correctly, an electric current is conducted through the tissue via the needle, resulting in mechanical friction, which heats the cells up and kills or damages them depending on the temperature—when these cells do scatter, they don’t grow, and therefore they can do no damage, says Hans Wiksell, a professor emeritus at Stockholm’s Karolinska Institutet who built the PRFA machine.

The electrode-needle brings the central body of the tumour to 70C, which quickly kills all the cells within, while the temperature in the zone immediately outside of the tumour is ideally 43C, where non-cancerous cells can repair the damage but cancerous ones will not.

“The wonderful thing is that the precision and control involved create a totally different mechanism to treat breast cancer,” explains Professor Wiksell. “You can get cancer from chemotherapy and radiation—nuclear bombs can cause cancer but heat can’t.”

So far, the current trial has tested the procedure on 18 older patients, including Margareta, with tumours that are no more than two centimetres in depth, and has boasted a high success rate, where participants have not seen regressions. The trial is limited because older patients tend to have tumours that aren’t as virulent and fast-spreading as those seen in younger ones.

As for Margareta, she was a bit startled by all the people, computers and other machines in the operating room. Then she closed her eyes and didn’t feel anything at all; barely 20 minutes later, it was all over.

Now cancer-free for five years, she says, “I’m very lucky and grateful that I could be in this trial. I can be there for my daughter, my three grand-children and Jackie, my Jack Russell terrier. I can keep on living.”

 

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