Breast cancer becomes deadly when it metastasizes—spreads to other parts of the body. For decades, we’ve been focused on developing treatments that will keep early-stage breast cancer from recurring. Now, researchers are spending more time studying how and where cancer cells spreads, with the goal of developing treatments that may cure, or at least stabilize, metastatic breast cancer.
We often talk about how there isn’t just one type of breast cancer, but instead different molecular subtypes that respond to different types of treatments and behave in different ways. These differences also affect where the cells that manage to leave the primary tumor and enter the bloodstream end up. Hormone-sensitive breast cancer (ER+ and/or PR+) has a tendency to show up in the skin and bone, whereas HER2-positive and triple-negative tumors are more likely to spread to the brain and the liver.
Breast cancer cells that can spread to the brain require particular skills to survive and grow in the brain microenvironment. One of the things they do is hijack astrocytes (they look like stars) that secrete factors to support their growth. By learning more about how cancer cells develop these skills, we might be able to figure out how to better treat or prevent these metastases.
The brain has unique mechanisms of protection. The most studied is the blood-brain barrier. Although its name makes it sound like a strong wall, the blood-brain barrier is actually a network of blood vessels that contains a unique lining of cells that have the ability to control what gets into, and what is kept out of, the brain. I think of it as the palace guards protecting the castle.
HER2-positive and triple negative tumors, seem to have an easier time getting past this barrier than other types of breast cancer cells—which is why women and men with these types of tumors are more likely to develop brain metastases. Another factor: many chemotherapy drugs are not able to cross the blood-brain barrier. Trastuzumab (Herceptin) seems to have a difficult time getting through, too. That’s why the standard treatments for brain metastases have been surgery, when possible, whole brain radiation, and most recently stereotactic radiosurgery (radiation that targets the metastases).
Clearly, new treatments are needed. That’s where Drs. Pat Steeg and Alexandra Zimmer at the National Institutes of Health (NIH) come in. Dr. Steeg’s research found that temozolomide, an oral drug approved by the FDA to treat brain tumors could prevent brain metastases from developing in mice. Now, she and Dr. Zimmer are conducting at clinical trial at the NIH to see if temozolomide can prevent brain metastases in breast cancer patients. The study has two parts. The first part will evaluate the safety and best dose of temozolomide when it is given along with T-DM1 (Kadcyla), a drug approved by the FDA to treat metastatic breast cancer. The second part of the study will compare temozolomide and T-DM1 to T-DM1 alone for preventing new brain metastases. Both parts of the study will enroll patients with HER2-positive breast cancer that has spread to the brain and who have already had their brain metastases treated with stereotactic radiation or surgery. The study will take place at the NIH in Bethesda, Maryland.
Dr. Susan Love Foundation for Breast Cancer Research’s Army of Women is helping Drs. Steeg and Zimmer find women and men with previously treated breast cancer brain metastases who are interested in enrolling in this study. So, let’s show them what our Army of Women can do! Help us spread the word about this study online, in chat rooms, on social media, and in your support groups. Tell your oncology care team about it, too. We owe it to everyone living with metastatic breast cancer to not only demand novel research but to do everything we can to help get it done!