Currently considered an incurable disease, there is a lot of work being done around developing better treatment options for metastatic breast cancer, and, ultimately, a cure. Numerous promising candidates are in clinical trials, all with the hope of progressing toward U.S. Food and Drug Administration (FDA) approval.
According to the World Health Organization (WHO), 2.3 million women were diagnosed with breast cancer in 2020, leading to 685,000 deaths globally. Figures from 2020 also showed that an estimated 168,000 women in the U.S. were living with metastatic breast cancer – the most advanced form of the disease. In addition, one in three breast cancer survivors are likely to be diagnosed with a recurrence of their cancer, which can present itself in other organs of the body and be metastatic.
Also referred to as stage 4 breast cancer, metastatic breast cancer means that the cancer – which originated in the breast – has spread to other parts of the body. This usually includes the lungs, liver, bones, or brain.
Metastatic breast cancer cancer is very complicated to treat, and, with no available cure, healthcare providers generally focus on giving treatments that cause the fewest possible side effects while helping people live as long as possible.
Current treatment options for metastatic breast cancer
Currently, the main approaches to treating metastatic breast cancer include systemic treatments that are designed to combat cancer cells regardless of their location within the body.
Laura Ramos, Research and Healthcare data analyst, Oncology, at Clarivate, who specializes primarily in breast cancer research, explained: “The selection of a therapeutic strategy for patients with metastatic breast cancer will be based on several factors, including the biology of the tumor, the presence of biomarkers, and other clinical factors. In most cases, patients will receive systemic treatment consisting of chemotherapy, endocrine therapy (in the case of hormone-sensitive cancers), targeted therapies, or best supportive care.”
In breast cancer, the cancer cells can have estrogen receptors (ER) or progesterone receptors (PR), which basically means that the cells have receptors that allow them to use either estrogen or progesterone to grow. Additionally, the cancer can either be HER2-positive or HER2-negative; HER2 is a protein that helps breast cancer cells grow quickly. Meanwhile, triple-negative breast cancer means the cancer cells do not have ER or PR receptors, and also do not make any or too much HER2. This type of breast cancer tends to grow or spread faster, and comes with fewer treatment options.
“In patients with estrogen receptor (ER)-positive, HER2-negative breast cancer subtype, CDK4/6 inhibitors combined with endocrine therapy constitutes the standard of care as a first-line therapy (initial treatment); HER2-positive patients are treated with anti-HER2 therapy; and, in triple-negative breast cancer patients, an initial treatment with chemotherapy, with or without immunotherapy is generally recommended,” said Ramos.
Monique Gary, breast surgical oncologist and medical director of the Grand View Health cancer program, also said that surgery or radiation therapy might also come into play in the comprehensive treatment strategy for metastatic breast cancer. “While these may be palliative, they can provide symptomatic relief, shrink tumors, and help extend life and the benefits of systemic therapy.”
“It really takes these multidimensional approaches and strong communication with the entire medical team to provide the most effective and personalized care for individuals facing this challenging stage of breast cancer,” she said.
Clinical trials show promising results for metastatic breast cancer
There are numerous clinical trials taking place for advanced-stage breast cancer, each one hoping to advance an evermore effective candidate, and there has actually been a lot of success in recent years in developing better therapeutic approaches for metastatic breast cancer.
For example, just this year, the FDA approved a new targeted therapy for hard-to-treat advanced breast cancers, including in patients with metastatic disease. The drug, called elacestrant, was developed by Stemline Therapeutics – a wholly-owned subsidiary of the Menarini Group. It became the first ever therapy specifically indicated for patients with ESR1 mutations in ER-positive, HER2-negative advanced or metastatic breast cancer.
Last year, a phase 3 trial, sponsored by the pharmaceutical companies Daiichi Sankyo and AstraZeneca and led by Dr. Shanu Modi of Memorial Sloan Kettering Cancer Center, also showed positive results for metastatic breast cancer; this time in patients who had HER2-low cancer. It involved 557 patients, with two-thirds receiving the experimental drug called trastuzumab deruxtecan, and the rest receiving standard chemotherapy.
In patients who took trastuzumab deruxtecan, their tumors stopped growing for around 10 months, compared to only five months for those who only received chemotherapy. Additionally, patients who received the experimental drug survived for around 23.9 months, while patients receiving chemotherapy only survived for around 16.8 months. Sold under the brand name Enhertu, the drug was approved by the FDA last year as the first HER2-directed therapy for patients with HER2-low metastatic breast cancer.
Meanwhile, biotech company BriaCell Therapeutics just announced earlier this month that its registration-enabling pivotal phase 3 study of its lead clinical candidate, Bria-IMT, in combination with Incyte’s checkpoint inhibitor, retifanlimab, was fully approved by the Institutional Review Board (IRB), and will soon enroll patients with advanced metastatic breast cancer. Bria-IMT is a targeted immunotherapy drug and has received a Fast Track Designation from the FDA. The successful completion of this study would allow BriaCell to subsequently submit a Biologics License Application and accelerate the path to commercialization.
These are just a few examples showing the current clinical trial landscape for metastatic breast cancer, and there are many more ongoing studies being conducted for the indication.
“Many of them (trials) are addressing targeted therapies, like pembrolizumab, letrozole, and ribociclib showing significant progress in reporting events like ‘progression-free survival,’ and studies are showing long-term safety, as patients may be on these drugs for very long time, or until no further benefit is determined,” said Gary.
“Additionally, there are some promising studies looking at antibody drug conjugates for metastatic breast cancer with really promising results. Encouragingly, trials are beginning to look at other factors that are important to patients, including quality of life, the benefits of diet and exercise, as well as mindfulness, and more research is being directed toward metastatic breast cancer than ever before. And stage 4, as we all know, deserves more.”
How close are we to finding a cure for metastatic breast cancer?
Finding an actual ‘cure’ for metastatic breast cancer is extremely difficult, largely due to the complexity of the disease and how advanced the cancer is at that stage. Therefore, the reality is that, despite the numerous clinical trials hoping to find better treatment options for metastatic breast cancer, a curative option is probably a long way off from being approved.
There was, however, some positive news recently regarding a potential new curative treatment approach for metastatic breast cancer. This came from researchers at Washington University School of Medicine in St. Louis, in the U.S., who managed to identify a way to treat the area surrounding breast tumors that have spread to the bone so that the tumors become vulnerable to attack by the immune system. The researchers boosted the activity of certain immune cells – T cells and macrophages – and these immune cells worked together to clear metastatic breast tumors that had spread to the bones of mice, and continued to eliminate tumor cells that eventually returned.
“Our study suggests we may be able to use two treatments – one to sensitize the myeloid tumor microenvironment to immunotherapy, and one to activate T cells – to target these bone metastases in a way that eliminates the tumor, prevents the cancer from returning and protects against bone loss in the process,” commented senior author of the study, Sheila A. Stewart.
Although this research is still in the very early stages, it could one day lead to a clinical trial investigating this strategy in patients with metastatic breast cancer, as long as it attracts the interest of biotech companies.
Ultimately, though, looking to the present and the near future, there is still a lot to be hopeful about regarding the prognosis and treatment options for people with metastatic breast cancer, even though these treatments are not necessarily curative.
A recent study from the National Cancer Institute found that the five-year survival rate of women diagnosed with metastatic breast cancer is increasing, and some women may even live for 10 years or more after being diagnosed.
“The landscape of targeted agents for metastatic disease is expected to rapidly expand in the next decade,” said Ramos. “In addition, an increasing number of strategies are being developed with the potential of diagnosing metastatic disease at an earlier stage. These strategies include the use of artificial intelligence and machine learning in cancer imaging or the assessment of circulating tumor DNA to predict relapse or guide treatment sequencing.”
“These are very exciting advances that will lead to a more effective control of the disease and potentially higher number of long-term survivors,” concluded Ramos.
Gary agrees with this sentiment: “The development of effective treatments for metastatic breast cancer continues to be an active area of research, and new therapies and approaches are being investigated. This progress represents a beacon of hope. With every discovery, we inch closer to the possibility of a curative breakthrough.”