Advances in research continue to change the treatment landscape and improve outcomes
Key takeaways
- Metastatic breast cancer, also known as stage 4, is treatable, but it is not yet curable.
- The Breast Cancer Research Foundation is the largest private funder of metastatic breast cancer research in the world.
- Here, find the latest on metastatic breast cancer research, including recent FDA-approved treatments and clinical trials of note.
More and more patients are living longer with metastatic breast cancer (MBC), also known as stage 4 or advanced breast cancer, as researchers are steadily advancing our understanding of the disease and finding more therapeutic strategies to treat it. In fact, there are more treatments available now than ever before. While MBC can be treated, it remains incurable, making it a leading cause of breast cancer deaths. It remains an urgent priority for Breast Cancer Research Foundation (BCRF) researchers.
In the U.S. today, there are an estimated 170,000 women living with metastatic breast cancer. And, about 1 in 3 breast cancer survivors will be diagnosed with a recurrence (cancer that has come back after a diagnosis and treatment), which can metastasize (spread) to other organs of the body.
Keep in mind that the rate of recurrence varies based on many factors including subtype, age, treatment availability and adherence, among others. Alarmingly, in recent years, there has been a rise in metastatic breast cancer diagnoses in younger women.
What metastatic breast cancer actually is
Metastatic breast cancer, also called stage 4 or advanced breast cancer, is when cancer that initially started in the breast spreads to other areas of the body. Metastasis occurs when breast cancer cells break away from the original tumor or nearby lymph nodes (found under the arm, inside the breast, and near the collarbone). The breast tumor cells then enter the bloodstream or lymphatic system, travel to other organs, and begin to grow. Doctors most commonly find breast cancer metastases in the bones, lungs, liver, and/or brain.
Only 6-10% of women have cancer that has already spread upon diagnosis, known as de novo metastatic breast cancer. However, nearly 30% of women diagnosed with early-stage breast cancer (stages 1-3) will see their disease metastasize.
The scale of the challenge
In the U.S. today, there are an estimated 170,000 women living with metastatic breast cancer and about 1 in 3 breast cancer survivors will be diagnosed with a recurrence that can metastasize to other organs of the body. According to the Centers for Disease Control and Prevention (CDC), metastatic incidence rose from 5.8 to 7.9 per 100,000 females between 2001 and 2021. While the American Cancer Society data shows that the five-year relative survival rate is 33%, metastatic breast cancer remains incurable.
Why MBC has been so difficult to treat
Advanced breast cancer remains a challenge to treat for several reasons. Metastatic breast cancer cells often develop resistance to treatments that may have successfully worked on the original tumor. BCRF-funded studies by AURORA EU and US have also revealed that the tumor biology of the primary cells can change as they metastasize—this can occur in as much as 30% of primary cells. In fact, tumors can switch subtypes between primary and metastatic sites, requiring a different treatment approach.
The tumor microenvironment and drug resistance
The tumor immune cell microenvironment can contribute to drug resistance and recurrence as immune-related gene expression shifts significantly between the primary, or first, and metastatic tumors. For these and other reasons, treating metastatic breast cancer solely based on the primary tumor biopsy can result in suboptimal therapy.
How researchers are attacking the problem today
Metastatic breast cancer research is an area of focus for BCRF. Investigators are seeking strategies that address advanced breast cancer and ways to personalize care for patients. This includes research in large-scale molecular profiling, testing new drugs and new combination treatments through clinical trials, and expanding the reach of developments through international data-sharing. BCRF is the largest private funder of metastatic breast cancer research in the world, supporting investigators dedicated to unraveling why some breast cancers spread. This year, the BCRF is dedicating almost $25 million across 102 projects to this area of study.
BCRF investigators are examining all aspects of stage 4 breast cancer, specifically including:
- Understanding the biology of metastasis and identifying distinct molecules that facilitate this process
- Identifying treatment targets and mechanisms of resistance
- Developing novel therapies or treatment combinations to treat the disease
- Improving the quality of life for patients living with metastatic breast cancer
- Understanding the characteristics of metastatic breast cancer in Black patients to improve our understanding of their disparate outcomes and inform novel treatment strategies for this patient population
Mapping metastasis at the molecular level: The AURORA programs
BCRF supports several large initiatives through our flagship Evelyn H. Lauder Founder’s Fund for Metastatic Breast Cancer Research. To date, BCRF has invested over $48 million in this initiative. Under the Founder’s Fund umbrella are the AURORA EU and US programs. AURORA EU is a large collaboration of researchers from 60 hospitals across 11 European countries and is led by the Breast International Group. AURORA US is coordinated through the Translational Breast Cancer Research Consortium which involves 18 institutions across the U.S. Together, they represent the largest global effort to compare matched primary and metastatic tumor samples.
Antibody drug conjugates: A class of targeted treatment
Antibody drug conjugates (ADCs) are targeted therapies engineered to deliver drugs to cancer cells with substantially less toxicity to surrounding normal cells. ADCs are composed of three parts: an antibody, a drug or payload, and a dissolvable linker that connects the antibody to the drug.
- The first HER2-directed ADC was Kadcycla (TDM-1, trastuzumab emtansine) which was granted FDA approval based on two pivotal trials, EMILIA and KATHERINE.
- Enhertu (trastuzumab deruxtecan) was then approved based on the results of the DESTINY-Breast04 study. This practice-changing trial demonstrated that Enhertu significantly improved progression-free survival for HER2-low patients.
- The first TROP2-directed ADC, Trodelvy (sacituzumab govitecan) gained FDA approval for treating metastatic triple-negative breast cancer (mTNBC) based on the ASCENT trials.
- Most recently, Datroway (dato-DXd, datopotamab deruxtecan) gained FDA approval based on the TROPION trials. Notably, Datroway is the first ADC that demonstrated efficacy as a first-line option for triple-negative breast cancer (TNBC).
Immunotherapy and combination approaches
Immunotherapies are drugs that harness a patient’s immune system to work against their cancer. The immune system is part of our body’s natural defenses against foreign substances. As researchers discovered the components of the immune system and how they work together to stave off infections, they developed strategies to use it against cancer.
What emerged was an immunotherapy, Keytruda (pembrolizumab), which is specific for PD-L1-positive tumors. Long-term results from KEYNOTE-355 confirmed Keytruda plus chemotherapy as a standard first-line option for patients with PD-L1-positive mTNBC, yielding a 27% reduction in risk of death. And the ASCENT-04 trial demonstrated the efficacy of pairing Keytruda with Trodelvy and led to the combination’s approval for treating certain mTNBCs.
Liquid biopsy and real-time precision medicine
A liquid biopsy is commonly used in clinical and laboratory research to identify and measure biomarkers. These blood-based tests give researchers the ability to look at the unique characteristics of a cancer cell, without performing an invasive procedure. Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are biomarkers that can be detected in the blood. The presence of CTCs has been shown to predict recurrence after treatment of early-stage breast cancer, and changes in the number of CTCs during treatment can indicate that a tumor is not responding to treatment or has spread to other tissues. CtDNA from blood samples can reveal how metastatic tumors are evolving without the need for a repeat biopsy. The use of ctDNA as a tool for tracking treatment response has been gaining traction.
Most recently, the FDA granted accelerated approval to Etcamah (camizestrant), in combination with a CDK4/6 inhibitor (abemaciclib, palbociclib, or ribociclib) for adults with hormone receptor (HR)-positive/HER2-negative, locally advanced or metastatic breast cancer with an estrogen receptor-1 (ESR1) mutation acquired during treatment—specifically, aromatase inhibitor and CDK 4/6 inhibitor therapy. The SERENA-6 study showed that switching therapy based on finding ctDNA of ESR1 mutations led to median progression-free survival of 16 months in those treated with Etcamah plus CDK4/6 inhibitor, compared to 9.2 months with aromatase inhibitor plus CDK4/6 inhibitor.
Persistent misconceptions about metastatic breast cancer
Misconception 1: MBC means untreatable disease. If caught early, breast cancer has a high likelihood of being cured, but, devastatingly, an estimated 42,670 people will die from it this year—the vast majority from metastatic breast cancer (also known as stage 4 breast cancer). Thanks to research, it can be treated, but it cannot yet be cured. While the exact number is unknowable, using statistical models based on incidence, survival, and mortality data, researchers estimate that about 170,000 people are currently living with MBC in the U.S. MBC is a major research priority for BCRF, and we’re proud to be the largest private funder of stage 4 breast cancer research in the world.
Misconception: Having MBC means something went wrong with screening or early treatment. But metastasis can occur even when earlier treatment was appropriate, as cancer cells can remain dormant for years and reactivate—a biological process researchers are actively studying.
Misconception: Research funding for MBC is proportional to its mortality impact. It is not: Historically, a disproportionately small share of breast cancer research funding has been directed to metastatic disease relative to its role as the cause of nearly all breast cancer deaths. BCRF deliberately allocates nearly one-third of annual funding to MBC research in a direct response to this gap.
What’s next in research
BCRF investigators are examining all aspects of stage 4 breast cancer, including:
- Understanding the biology of metastasis and identifying distinct molecules that facilitate this process
- Identifying treatment targets and mechanisms of resistance
- Developing novel therapies or treatment combinations to treat the disease
- Improving the quality of life for patients living with metastatic breast cancer
- Understanding the characteristics of metastatic breast cancer in Black patients to improve understanding of their disparate outcomes and inform novel treatment strategies for this patient population
BCRF-funded trials, additional data from AURORA EU and US, and an increase in targeted drug approvals for metastatic breast cancer mean the treatment landscape today is dramatically different from a decade ago. With continued support for research, investigators can pursue more lines of study and help give patients with advanced breast cancer more time and a better quality of life.
Breast cancer that has metastasized to the brain presents a unique challenge, as many treatments cannot cross into the brain. Research is changing that. In fact, most recently, the FDA approved a first-line maintenance treatment combination for patients with metastatic or locally advanced HER2-positive breast cancer, including those with brain metastases: The maintenance treatment includes the use of tucatinib (Tukysa®) in combination with trastuzumab and pertuzumab.
Treatment approval was based on results from the HER2CLIMB-05 trial which showed that adding tucatinib to the maintenance treatment regimen reduced the risk of disease progression or death by 36%. Patients treated with tucatinib had a median of 24.9 months of progression-free survival, as opposed to 16.3 months among those given the placebo. Long-term follow-up is underway.
BCRF-funded trials, additional data from AURORA EU and US, and an increase in targeted drug approvals for MBC mean the treatment landscape today is dramatically different from a decade ago. With continued support for research, investigators can pursue several lines of study as they seek to give patients with MBC more time and a better quality of life.
Support the research that makes better survivorship outcomes possible. Donate, start a fundraiser, or explore other ways to give to BCRF today.
Frequently Asked Questions
Currently, in the U.S. the five-year relative survival rate for patients with metastatic breast cancer is approximately 34%. The latest available data from the National Cancer Institute’s SEER program report 33.8% for women diagnosed with distant-stage breast cancer between 2016 and 2022. There is some variability between subtypes with HR-positive/HER2-positive MBC having the highest (45.6%) and mTNBC having the lowest (12.8%) 5-year survival rate. It is important to recognize that historical survival statistics may not fully capture outcomes as the treatment landscape is constantly evolving.
The key difference is how much HER2 protein the cancer cells express and is determined by a pathology classification system. HER2-positive disease has high HER2 expression or gene amplification, whereas HER2-low disease has lower levels of HER2 and is classified as HER2-negative, traditionally. The levels of HER2 can help determine which treatments are likely to work, so the distinction is particularly important when selecting treatment and interpreting clinical trial eligibility.
Yes. Metastatic breast cancer can go into remission, sometimes even complete remission that lasts for many years. However, remission does not necessarily mean the cancer has been cured, because microscopic cancer cells may remain even when scans show no evidence of disease. MBC is therefore generally considered treatable but not curable.
The main difference is that ADCs are targeted whereas chemotherapy is not: ADCs use an antibody to deliver a potent chemotherapy drug to cancer cells, whereas traditional chemotherapy circulates through the body and affects rapidly dividing cells, not just cancer cells. While ADCs are designed to make treatment more targeted, they can still cause significant side effects.
As mentioned above, BCRF’s approach is multifold, supporting a myriad of topics important for understanding and effectively treating MBC, including: Understanding the biology of metastasis and identifying distinct molecules that facilitate this process; identifying treatment targets and mechanisms of resistance; developing novel therapies or treatment combinations to treat the disease; improving the quality of life for patients living with metastatic breast cancer; and understanding the characteristics of metastatic breast cancer in Black patients to improve our understanding of their disparate outcomes and inform novel treatment strategies for this patient population.
Selected References 
AURORA EU Scope & Data: Caballero et al. (2023). “International research to address the challenges of metastatic breast cancer: the AURORA Program (BIG 14-01).” npj Breast Cancer. DOI: 10.1038/s41523-023-00548-9.
Drug Approvals & Advancements: PMC12941040 (2025). “A Systematic Review of Major Advances in Breast Cancer Therapeutics in 2025.” PubMed Central.
Incidence Rates: CDC (November 2024). “Metastatic Female Breast Cancer Incidence.” U.S. Cancer Statistics.
MBC Demographics: National Breast Cancer Foundation (2026). “Breast Cancer Facts and Stats.”
Ismaili N. (2026). A Systematic Review of Major Advances in Breast Cancer Therapeutics in 2025: Synthesis of Conference and Published Evidence. International journal of molecular sciences, 27(4), 1971. https://doi.org/10.3390/ijms27041971
Survival Rates: American Cancer Society. “Survival Rates for Breast Cancer: “https://www.cancer.org/cancer/types/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-survival-rates.html
Trial Breakthroughs: BCRF (March 2026). “5 Breast Cancer Breakthroughs from 2025.”
Tumor Microenvironment & Liquid Biopsy: PMC13343184 (2025-26). “Turmoil and breakthroughs: Highlights and growing pains in breast cancer therapy 2025-2026.” PubMed Central.
