Emerging Therapies in Metastatic Breast Cancer Research

Research studies help identify critical aspects of the disease

Metastasis is a complicated process with many steps, beginning with the breast cancer cells breaking away from the primary tumor and entering the blood or lymphatic system. Not every tumor cell that that enters the circulation, however will form a tumor somewhere else in the body. In fact, few do.

The most common sites for breast cancer metastasis are the brain, lung, bone and liver, but there are many obstacles a tumor cell must overcome on the journey to these distant places. The blood stream is a harsh environment for a tumor cell to survive in. From there, the tumor cell has to make a safe landing, burrow through the wall of the blood vessel, tether itself to completely different tissue and go about the business of multiplying to make more tumor cells and ultimately a tumor. To picture this journey, one might imagine being caught in a rough river current without a life vest; trying to grab hold of a branch against the rapid forces of the water and not only hang on, but get to shore and stand up– only to find a very unfamiliar landscape and potentially unfriendly residents, who threatened by the outsider, call in the local law enforcement.

You might imagine that it would take a crafty–even arrogant, well-trained or gifted athlete to survive such a dangerous journey, but it could also be someone with an insurmountable will to live who finds the means to survive beyond all explainable physical capacity.

And so it is that the tumor cells that survive the journey have an unusual and robust capacity to survive, and scientists still don’t fully understand how.

Also known as stage IV breast cancer and advanced breast cancer, MBC is a treatable but still incurable disease and is the cause of virtually all deaths from breast cancer. We don’t currently know how many people are living with MBC, but up to 30 percent of the 3.5 million women and men in the US with a history of breast cancer may ultimately be diagnosed with a reoccurrence and metastatic disease.

While there is much to learn about the metastatic process, research studies have identified critical aspects of the disease, including:

1) Metastatic breast tumors have unique molecular profiles from the primary (originating tumor), indicating that tumor cells evolve over time to acquire cell growth and survival advantages.

2) The metastatic process involves specialized cells called tumor initiating, or cancer stem cells.

3) Normal, healthy cells that are not part of the tumor act to assist metastasis both at the primary cancer site and the metastatic site.

This tumor evolution and cooperativity helps to explain why metastatic breast cancers can be more aggressive and difficult to treat than the original cancer and why a single drug is not likely to be effective. Many in the field agree that combination approaches are likely to be most effective in MBC due to the diverse drivers of the disease, its complicated biology and the often complicated treatment history of an individual patient.

While research continues to unravel the mysteries of metastasis, those living with metastatic breast cancer–an estimated 155,000 women and men–are in urgent need of new therapies.

Advances in technologies that allow scientists to probe the DNA of individual cells have paved the way for the development of targeted therapies- drugs designed to hit specific targets that are the bad actors driving cancer growth.

Several exciting new therapies are showing promise in treatment of MBC. One is a class of drugs called CDK4/6 inhibitors. Examples include Ibrance® (palbociclib), that is FDA approved for metastatic ER-positive breast cancer; Opdivo® (Nivolumab), FDA approved to treat melanoma, Hodgkin’s lymphoma, and other cancers, as well as ribociclib and abemaciclib- both in clinical trials for breast cancer. These drugs work by shutting down tumor cell division, a key component of growth.  

New immunotherapy approaches that enhance the body’s own ability to identify tumors and fight off cancer may improve the effectiveness of chemo or radiation therapies. Clinical trials in patients with metastatic breast cancer are ongoing to test a class of drugs called PD1/PD-L1 inhibitors, such as Keytruda® (Pembrolizumab) and Tecentriq® (Atezolizumab), both approved for treatment of metastatic lung cancer. Vaccines derived from immune factors from patients’ blood are also being explored in combination with other immunotherapies and chemotherapy in clinical trials of MBC. 

These are exciting advances in treating metastatic breast cancer, but these therapies do not work for every tumor or every patient. The only way to find new therapies for MBC and determine which patients are likely to benefit is through research and clinical trials. MBC patients who are interested in participating in a clinical trial can search all the active trials, at www.breastcancertrials.org, www.breastcancertrials.org, a patient centered search tool designed for patients with MBC to help them find clinical trials that are right for them. Patients may still find it difficult to participate if there is not a research hospital center close to them or because of other barriers. Another resource that can help patients engage in research is the Metastatic Breast Cancer Project, www.mbcproject.org that uses an internet- based platform to connect metastatic breast cancer patients around the world with scientists using cutting-edge technology to study cancer’s genetic and molecular causes. 

Just as breast cancer is not one disease, metastatic breast cancer is not one disease.  Research has made great strides in unraveling its intricacies, but much more needs to be done. Because the government is the largest funder of cancer research, Congress cannot lose sight of the continued urgency to end this disease. The Precision Medicine Initiative and National Cancer Moonshot are steps in the right direction. Read more about BCRF’s support of metastatic research here.

Watch one woman’s journey with metastatic disease here on VeryWell.com.