Metastatic Breast Cancer: Symptoms, Treatment, Research

What is metastatic breast cancer? Learn more about stage 4 breast cancer and what BCRF is doing to accelerate lifesaving research

Metastatic breast cancer is an urgent priority for BCRF researchers as the leading cause of breast cancer deaths. While it can be treated—with more therapies and drugs available now than ever before—metastatic breast cancer remains incurable.

In the U.S. today, there are an estimated 200,000 women living with metastatic breast cancer, also called stage 4 breast cancer or advanced breast cancer. In addition, about one in three 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, the rate of recurrence is variable 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 young women.

Developing strategies to treat metastatic breast cancer patients and advancing our understanding of the disease is a major focus for breast cancer researchers. Read more about the signs that breast cancer has spread and how BCRF-supported researchers are making progress against it.

Key Takeaways

• Metastatic breast cancer (stage 4) occurs when breast cancer spreads to other parts of the body; it is treatable but not yet curable.
• Symptoms vary by where the cancer has spread, with common signs including bone pain, headaches or vision changes, jaundice, chest pain, or persistent cough.
• More treatment options exist than ever before, including hormone therapy, chemotherapy, targeted therapies, immunotherapy, and radiation or surgery for symptom relief.
• BCRF is the largest private funder of metastatic breast cancer research, driving major breakthroughs and expanding treatment options through global studies and innovative science.

What is metastatic breast cancer?

Metastatic 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 to 10 percent of women are first diagnosed with stage 4 breast cancer, called de novo metastatic breast cancer. However, nearly 30 percent of women diagnosed with early-stage breast cancer (stages 1-3) will see their disease metastasize.

Metastatic Breast Cancer Symptoms

The early signs of metastatic breast cancer may vary depending on how far the breast cancer has spread and what area/type of tissue the cancer has invaded. Non-specific symptoms of stage 4 breast cancer can include fatigue, weight loss, and poor appetite, but these may also be caused by medication, depression, and other conditions.

The most common metastatic breast cancer symptoms are listed below.

Bone metastasis symptoms:

• bones are more easily fractured or broken
• swelling
• sudden, noticeable progressive bone pain

Brain metastasis symptoms:

• persistent and progressively worsening headache
• problems with speech or vision
• vomiting or nausea
• seizures
• behavioral changes
• memory problems

Liver metastasis symptoms:

• itchy skin or rash
• jaundice
• abdominal pain, vomiting, or nausea
• abnormally high liver enzymes in the blood

Lung metastasis symptoms:

• chest pain
• chronic cough or shortness of breath
• abnormal chest X-ray

If you are currently undergoing treatment for breast cancer and experience any of these signs of stage 4 breast cancer, talk to your doctor right away. Early detection is important to ensure you’re getting the best treatment for metastatic breast cancer. If you are a breast cancer survivor or if members of your immediate family have been impacted by the disease and you begin experiencing any of the above symptoms, be sure your doctor knows your personal or family history of breast cancer.

How is metastatic breast cancer diagnosed?

If your doctor has reason to suspect your disease has metastasized (or that you may have de novo metastatic breast cancer) and you have any of the above signs that your breast cancer has spread, he or she may perform follow-up tests. These include imaging tests, blood tests, and biopsies of the suspected metastatic lesion.

For metastatic breast cancer symptoms that point to possible brain involvement, doctors will perform a brain MRI and, in rare cases, when possible, a brain biopsy. If your doctor suspects potential bone, lung, or liver involvement, he or she may use several types of imaging tests, including MRI, CT, or PET, and then perform a biopsy.  For suspected lung or liver metastases, doctors will order bronchoscopy or a mucous exam and liver function tests or an ultrasound, respectively. There are also additional imaging tests (i.e., bone scans or X-rays) and blood tests to specifically diagnose metastatic breast cancer in bones.

RELATED: Clinical Challenges and Recent Advancements for Breast Cancer Brain Metastases

Metastatic Breast Cancer Treatment

While there is no cure for metastatic breast cancer, there are a variety of treatment options that prolong lives.

After a metastatic breast cancer diagnosis, doctors may use several treatment approaches depending on where the cancer has spread, its characteristics (such as hormone receptor or HER2 status), and prior treatments.

The most common treatments for stage 4 breast cancer are:

• Hormonal therapies: The first molecularly targeted drugs for breast cancer — including Nolvadex® (tamoxifen), Faslodex® (fulvestrant), or aromatase inhibitors such as Femara® (letrozole) — can help shrink or slow the growth of hormone receptor (HR)–positive metastatic breast cancer.

• Chemotherapy: Medications such as Adriamycin® (doxorubicin), Xeloda® (capecitabine), and Taxol® (paclitaxel) may be used alone or in combination with other drugs to treat metastatic breast cancer that is growing quickly or is present in significant amounts in organs.

There are also other therapies that target specific characteristics of cancer cells, such as proteins that allow cancer to grow unchecked. While chemotherapy does not distinguish between cancerous and non-cancerous cells and therefore can harm both, these targeted therapies are generally less likely to harm normal cells. There are more than a dozen such FDA-approved targeted therapies for metastatic breast cancer, including:

• antibodies that target HER2 and leverage the power of the patients’ immune system to fight cancer, such as Herceptin® (trastuzumab), Perjeta® (pertuzumab), and Keytruda® (pembrolizumab)
• antibody-drug conjugates that recognize specific targets on cancer cells and deliver toxic drugs directly to the tumor, such as HER2 receptor-targeted Enhertu® (trastuzumab deruxtecan) and Kadcyla® (trastuzumab emtansine) or TROP-2 protein-targeted Trodelvy® (sacituzumab govitecan)
• PARP inhibitors that target the PARP protein, an important enzyme involved in DNA repair, such as Lynparza® (olaparib) and Talzenna® (talazoparib) 
• CDK4/6 inhibitors that interrupt specific enzymes to slow or stop cancer cells from growing, such as Ibrance® (palbociclib), KISQALI® (ribociclib), and Verzenio® (abemaciclib)

These therapies can be used alone or in combination with chemotherapy to treat specific breast cancer subtypes:

• metastatic HR-positive/HER2-negative breast cancer (Inluriyo™ (imlunestrant), KISQALI, Lynparza, or Ibrance)
• metastatic HER2-positive breast cancer (Herceptin, Nerlynx® (neratinib maleate), or Perjeta)
• metastatic triple-negative breast cancer (Keytruda, Lynparza, or Trodelvy)

While surgery may be an option, it may not be the best one because it is unlikely to remove all cancer cells. However, some doctors recommend targeted surgery and/or radiation to alleviate pain or other specific symptoms. In addition, although doctors don’t commonly use other localized therapies (such as radiation therapy or ablation) to treat metastatic breast cancer, they may use them in certain circumstances, particularly when:

• tumors press on critical areas of the brain or spinal cord
• bone metastases weaken the bone so much that it is poses a risk of fracture
• lesions in the lungs make it hard to breathe
• or tumors interfere with normal liver function.

BCRF’s Focus on Metastatic Breast Cancer Research

BCRF is the largest private funder of metastatic breast cancer research in the world. This year, the Foundation is dedicating almost $25 million across 96 projects to this area of study.

“Virtually all deaths from cancer are from metastases—we lose about 43,000 people in the U.S. alone to metastatic breast cancer each year,” says Dr. Dorraya El-Ashry, BCRF Chief Scientific Officer. “That’s why metastatic breast cancer research remains a high priority at BCRF. These projects will help us understand the full spectrum of metastatic disease in order to both effectively treat it and ultimately prevent it altogether.”

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 our understanding of their disparate outcomes and inform novel treatment strategies for this patient population

The Evelyn H. Lauder founder’s fund: Accelerating discovery

In addition, 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. 

Founder’s Fund-supported studies led to the development of an experimental model system that precisely mimics human breast metastases as well as an open-access online database of metastases models. Both tools are readily available to the research community to further metastatic breast cancer research.

Global research initiatives: AURORA EU and AURORA US

The Founder’s Fund also supports the largest global effort to study metastatic breast cancer across Europe (AURORA EU) and the U.S. (AURORA US). These projects are designed to gain a deeper understanding of the molecular differences between primary and metastatic breast cancer.

AURORA EU is a large research initiative sponsored by the Breast International Group (BIG) that analyzes tumor and blood samples from metastatic breast cancer patients to better understand the disease, including how it progresses over time and why it responds well or not to specific treatments. It published its first findings in 2019.

AURORA US harnesses the extensive clinical trial infrastructure of the Translational Breast Cancer Research Consortium, a model clinical trials program accelerating advances in breast cancer care. It has two components: a retrospective analysis of primary and metastatic tumors, plus a prospective clinical study. It published its first findings in 2019.

Breakthrough Discoveries and New Treatments

While metastatic breast cancer has defied more simple solutions and is not yet curable, there is much to be hopeful about—especially recently. At the 2022 American Society of Clinical Oncology meeting, researchers, clinicians, and others heralded astonishing results from the DESTINY-Breast04 trial with a standing ovation: Researchers found that the drug Enhertu® significantly improved progression-free survival for patients with HER2-low metastatic cancer. Soon after, the FDA approved Enhertu for advanced HER2-low breast cancer. BCRF researchers and others continue working to more precisely define HER2-low so that more people can benefit from treatment with this drug. “This is an important study,” lead investigator Dr. Shanu Modi told BCRF in an interview. “We’ve opened up a new targetable population of patients within breast cancer. This is more than just about this drug and more than just about breast cancer. It’s about a huge advancement in cancer therapy in general.”

The pace of research in MBC has been accelerating. Since 2015, the FDA has approved 17 new drugs for this disease based on the clinical findings of BCRF investigators and other researchers. These include:

• CDK4/6 inhibitors Ibrance® (palbociclib), KISQALI® (ribociclib), and Verzenio® (abemaciclib) for treating estrogen receptor (ER)-positive metastatic breast cancer

• Nerlynx® (neratinib maleate) in combination with Xeloda® (capecitabine) for adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting

• PARP inhibitors Talzenna® (talazoparib) and Lynparza® (olaparib) for treating HER2-negative metastatic breast cancer

• P13K inhibitor Piqray® (alpelisib) for treating ER-positive/HER2-negative metastatic breast cancer

• Antibody-drug conjugate Enhertu® (trastuzumab deruxtecan) for metastatic HER2-positive breast cancer that has been treated with two or more anti-HER2 therapies and HER2-low breast cancer

• Immunotherapy drug Keytruda® (pembrolizumab) as well as an antibody-drug conjugate Trodelvy® (sacituzumab govitecan) for treating metastatic triple-negative breast cancer, an aggressive subtype

• Immunotherapy drug Margenza® (margetuximab) for treating HER2-positive advanced breast cancer

• A small molecule HER2 inhibitor Tukysa® (tucatinib) for treating HER2-positive breast cancer including those with brain metastases

• The first-in-class AKT inhibitor, Truqap® (capivasertib) in combination with Faslodex® (fulvestrant) for patients with HR-positive/HER2-negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN-alterations

• The novel oral selective estrogen receptor degrader (SERD) Orserdu® (elacestrant) for ER-positive/HER2-negative, ESR1-mutated advanced or metastatic breast cancer

• Itovebi® (inavolisib) with Ibrance® (palbociclib), and Faslodex® (fulvestrant) for endocrine-resistant, PIK3CA-mutated, HR-positive/HER2-negative, locally advanced or metastatic breast cancer

• A TROP 2-directed ADC, Datroway® (datopotamab deruxtecan) for patients with unresectable or metastatic, HR-positive/HER2-negative breast cancer who have received prior endocrine therapy and chemotherapy 

• A next generation SERD, Inluriyo® (imlunestrant), for treating patients with ER-positive/ HER2-negative advanced or metastatic breast cancer with ESR1 mutations that has progressed following at least one line of endocrine therapy

Looking ahead: Advancing toward a future without metastatic breast cancer

In addition, research is revealing that in certain patients—those with HER2-positive breast cancer—some metastases can be prevented. Research is the reason we are finally seeing real momentum in metastatic breast cancer research. We are on the cusp of groundbreaking developments in stage 4 breast cancer research, and BCRF is committed to leading the way.

Frequently asked questions about metastatic breast cancer

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Read More:

Our Commitment to Metastatic Breast Cancer Research
Metastasis: An Area of Focus for BCRF
Metastatic Breast Cancer Alliance
More BCRF-Curated Resources for People with Metastatic Breast Cancer
Dr. Martine Piccart Discusses AURORA EU on the BCRF Podcast