A better way to fight breast cancer that has spread to the brain


By Amy Norton
HealthDay reporter

MONDAY, Oct. 18, 2021 (HealthDay News) – Researchers may have found a noninvasive way to temporarily open the boundaries of the brain to allow drugs to fight the tumor inside.

Necessarily, the brain is protected by a layer of specialized cells called the blood-brain barrier. Its task is to pass the necessary substances – such as oxygen and sugar – while protecting against substances that could be toxic.

Unfortunately, this means that drugs often cannot penetrate the brain to a large extent to treat tumors or damaged tissue.

Scientists are now reporting for the first time: They used an advanced ultrasound technique to non-invasively and temporarily open the blood-brain barrier in four patients with breast cancer that has spread to the brain.

This allowed the researchers to deliver trastuzumab (Herceptin) to patients’ brain tumors.

The findings were published on October 13 in the journal Science of translational medicine, are preliminary and constitute only “proof of concept”.

“We are in the first stage, showing that this is possible and safe,” said senior researcher Dr. Neir Lipsman, a neurosurgeon and scientist at the Center for Health Sciences in Sunnybrook, Toronto.

But there have been signs that the technique is increasing the amount of drug that has reached brain tumors. On average, there was a slight decrease in the size of the patient’s brain tumor.

This finding should be interpreted with caution, the researchers stressed, but it lays the groundwork for larger studies.

Ultimately, Lipsman said, the goal is to show whether the technique improves long-term control of brain tumor growth and prolongs patient survival.

Breast cancer is very treatable, especially when caught early. Among women diagnosed when cancer is limited to the breast, 99% are still alive five years later, according to the American Cancer Society. This survival rate drops to 28% among women with metastatic breast cancer – meaning that tumors have developed in distant parts of the body, such as the brain.

The new study included four women with HER2-positive breast cancer that had spread to the brain. In HER2-positive breast cancer, tumor cells carry a specific protein (HER2) that helps them grow. Some drugs, such as Herceptin, target this protein.

However, only a relatively small amount of Herceptin can penetrate the brain, according to the Lipsman team.

Therefore, the researchers tested an approach to briefly open the protective border of the brain: “focused” ultrasound performed using MRI as a visual guide.

If the blood-brain barrier is presented as a layer of plastic sheath, Lipsman said, the technique essentially “dissolves” the plastic sheath in certain places — giving the drug a gateway to enter the brain.

“It closes within 24 hours,” Lipsman said.

Using advanced imaging techniques, the researchers were able to verify that the approach increased the amount of Herceptin that penetrates patients’ brain tumors. In the following months, all four women showed some reduction in the volume of their tumors.

“Of course,” Lipsman said, “the blood-brain barrier is there for some reason.” So the concern with opening it, even temporarily, is that toxins can be inadvertently infiltrated.

But there were no safety issues in this initial study.

Dr. Charles Shapiro is a professor and oncologist at Icahn Medical School in Mount Sinai in New York.

He said a number of drug combinations – including Herceptin, along with the drugs tucatinib (Tukysa) and capecitabine (Xeloda) – have “activity” against brain tumors in patients with HER2-positive breast cancer.

Shapiro also notes that when the cancer has spread to the brain, the blood-brain barrier is already “broken.” So whether this barrier-opening technique will ultimately improve the supply of drugs to the brain remains to be seen, said Shapiro, who was not involved in the study.

If further studies are promising, he said, then the latest test will be a “phase 3” trial, where patients will be randomly assigned to receive standard drug therapy with or without ultrasound.

And if the approach breaks out, Lipsman said it could potentially be used to treat not only tumors, but other brain conditions where drug delivery is difficult, such as Alzheimer’s or Parkinson’s.

More info

The American Cancer Society has more to treat advanced breast cancer.

SOURCES: Neir Lipsman, MD, neurosurgeon, scientist and director, Harquail Center for Neuromodulation, Sunnybrook Center for Health Sciences, Toronto, Canada; Charles Shapiro, MD, Professor of Medicine, Hematology and Medical Oncology, Icahn School of Medicine in Mount Sinai, New York; October 13, 2021 Science of translational medicine, online



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