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Metastatic Breast Cancer: Symptoms, Treatment, Research

By BCRF | February 27, 2024

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, one in three breast cancer survivors will be diagnosed with a recurrence (cancer that has come back after a diagnosis and treatment), which can present itself in other organs of the body and be metastatic. Alarmingly, in recent years, there has been a rise in metastatic breast cancer diagnoses in young women.

These devastating facts make developing promising strategies to treat metastatic breast cancer patients and advancing our understanding of the disease a major focus for breast cancer researchers. Read more about the signs that breast cancer has spread, about metastatic breast cancer symptoms, and how BCRF-supported researchers are making progress.

What is Metastatic Breast Cancer?

Metastatic breast cancer is when cancer, initially located in the breast, spreads to other areas of the body.

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 will see their disease metastasize and spread to other organs.

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 metastatic breast cancer in the bones, lungs, liver, and/or brain.

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 any number of other conditions.

The most common metastatic breast cancer symptoms are listed below, according to the area the cancer may have spread.

Metastasis to the bone:

  • Bones are more easily fractured or broken
  • Swelling
  • Sudden, noticeable progressive bone pain

Metastasis to the brain:

  • Persistent and progressively worsening headache
  • Problems with speech or vision
  • Vomiting or nausea
  • Seizures
  • Behavioral changes
  • Memory problems

Metastasis to the liver:

  • Itchy skin or rash
  • Jaundice
  • Abdominal pain, vomiting, or nausea
  • Abnormally high liver enzymes in the blood

Metastasis to the lung:

  • 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 discovery is important to ensure you’re getting the best treatment. 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, your doctor may perform follow-up tests. These include imaging tests, blood tests, and biopsies of the suspected metastatic lesion.

For metastatic breast cancer symptoms that indicate brain involvement, a brain MRI and, in rare cases where possible, a brain biopsy will be performed. For those symptoms that indicate bone, lung, or liver involvement, biopsies are performed, and several types of imaging tests may be used (MRI, CT, or PET). Additional imaging tests (i.e., bone scans or X-rays) and blood tests can be used to diagnose metastatic breast cancer in bones specifically. For suspected lung or liver metastases, doctors will order bronchoscopy or a mucous exam and liver function tests or an ultrasound, respectively.

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 employ several treatment approaches depending on where the cancer has spread, the cancer’s 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 tamoxifen, Faslodex®/fulvestrant, or aromatase inhibitors such as Femara®/letrozole—are used for treating hormone receptor (HR)–positive metastatic breast cancer to help shrink or slow cancer growth.
  • Chemotherapy agents such as doxorubicin, Xeloda®/capecitabine, and paclitaxel may be used alone and in combination with other drugs to treat metastatic breast cancer that is growing quickly or is present in significant amounts in organs.

Other therapies have been developed to 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:

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

  • Metastatic HR-positive/HER2-negative breast cancer (KISQALI®/ribociclib, Lynparza®/olaparib, or Ibrance®/palbociclib)
  • Metastatic HER2-positive breast cancer (Herceptin®/trastuzumab, Nerlynx®/neratinib or Perjeta®/pertuzumab)
  • Metastatic triple-negative breast cancer (Keytruda®/pembrolizumab or Lynparza®/olaparib)

While surgery may be an option, it may not be the best one because it is unlikely to excise all cancer cells. However, some doctors recommend targeted surgery and/or radiation to alleviate pain or other specific symptoms. In addition, although other localized therapies (radiation therapy, ablation, or chemotherapy) are not commonly used to treat metastatic breast cancer, they may be employed 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 and currently dedicates more than one-third of its total investment—$22.3 million across 83 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 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

In addition, BCRF supports several large initiatives through our flagship Evelyn H. Lauder Founder’s Fund for Metastatic Breast Cancer Research. 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 of these tools have been made readily available to the research community to further metastatic breast cancer research.

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 deep 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 2021.

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 is comprised of two components: a retrospective analysis of primary and metastatic tumors plus prospective clinical trials. It published its first findings in 2022.

While metastatic breast cancer has defied more simple solutions and remains incurable, there is much to be hopeful about—especially recently. At the 2022 American Society of Clinical Oncology meeting, researchers, clinicians, and others heralded the astonishing results from the DESTINY-Breast04 trial with a standing ovation, and just a few months later, the FDA approved the study’s drug, 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. It’s 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 2016, the FDA has approved 11 new drugs for this disease based on the clinical findings of BCRF investigators and other researchers. These include:

  • CDK4/6 inhibitors KISQALI®/ribociclib, and Verzenio®/abemaciclib for treating estrogen receptor–positive metastatic breast cancer
  • P13K inhibitor Piqray®/alpelisib for treating estrogen receptor-positive, HER2-negative metastatic breast cancer
  • PARP inhibitor Lynparza®/olaparib for treating HER2-negative metastatic breast cancer
  • Immunotherapy drugs Tecentriq®/atezolizumab and Keytruda®/pembrolizumab as well as an antibody-drug conjugate Trodelvy®/sacituzumab govitecan-hziy for treating metastatic triple-negative breast cancer, an aggressive subtype
  • Antibody-drug conjugate Enhertu®/fam-trastuzumab deruxtecan-nxki for metastatic HER2-positive breast cancer that has been treated with two or more anti-HER2 therapies and HER2-low breast cancer.
  • A small molecule HER2 inhibitor Tukysa®/tucatinib for treating HER2-positive breast cancer including those with brain metastases
  • The novel oral selective estrogen receptor (ER) degrader Orserdu®/elacestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer
  • 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

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.

Read More:
Selected References:

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Mariotto, A. B., Etzioni, R., Hurlbert, M., Penberthy, L., & Mayer, M. (2017). Estimation of the Number of Women Living with Metastatic Breast Cancer in the United States. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology26(6), 809–815.

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