Overview

Currently, around 155,000 women in the U.S. are living with metastatic breast cancer (MBC), which means their cancer has spread from the breast to other parts of the body, such as the bones and the lungs. Also known as "stage 4 breast cancer," MBS is not curable, but it is treatable, and new targeted therapies continue to slow progress of the disease and help women live longer.

What Is Metastatic Breast Cancer?

Metastatic breast cancer is cancer that has traveled (metastasized) through the lymph system or bloodstream to create tumors in other parts of the body, such as the liver, lungs, brain and bones. Although MBC has spread, it is still considered breast cancer and treated as such.

When Can Metastatic Breast Cancer Occur?

About 6% to 10% of women with MBC are diagnosed from the start with stage 4 breast cancer. This type is called de novo metastatic breast cancer. In most women, however, metastatic breast cancer occurs years after successful treatment of early stage breast cancer, which is called "distant recurrence." Between 20% and 30% of women who are diagnosed with early stage breast cancer go on to develop MBC.

Although the process leading to recurrence is not well understood, most metastatic breast cancers are cancerous cells that remained in the body after treatment for early stage disease and were not detected. These cells remained dormant (not active) for years but for some reason, they start to grow again and become stage 4 breast cancer.

The good news is that women are living longer with MBC. Currently, about one third of women in the U.S. with MBC will live at least five years after diagnosis and some live more than 10 years. Moreover, the development of innovative therapies continues to increase survival rates and improve quality of life.

Symptoms

Most often, metastatic breast cancer spreads to the bones, lungs, brain and liver, but the symptoms of MBC depend on where and how much the cancer has spread.

Symptoms of MBC include:

• Constant back, bone or joint pain
• Numbness or weakness anywhere in the body
• A constant dry cough
• Shortness of breath or difficulty breathing
• Loss of appetite
• Abdominal bloating, pain or tenderness
• Constant nausea, vomiting or weight loss
• Jaundice (a yellow tinge to the skin and whites of the eyes)
• Severe headaches
• Vision problems (blurry vision, double vision)
• Seizures
• Loss of balance
• Confusion

Diagnosis

To diagnose metastatic breast cancer, your health care team will conduct various tests. These may include chest X-rays, bone scans, CAT scans, PET scans, MRIs and blood tests.

After the diagnostic tests, the next step is to perform a biopsy to evaluate the features of the cancer and identify the subtype. The results are used to identify treatment options depending on the characteristics of the cancer cells (such as hormone receptor status and HER2 status).

Because your gene status may also determine your course of treatment, the following tests may be done to look for specific mutations in the cancer's genes:

• Genetic testing
  Recommended if there is a family history of breast cancer, this testing looks at the genes inherited from a person's parents.

• Genomic testing
  These tests look at the genes in breast cancer to determine what is causing the cancer to grow and understand how the cancer may respond to different therapies.
  
  
• Molecular testing of the tumor
  Laboratory tests on a sample of the cancerous tissue will identify specific genes, proteins and other factors unique to the tumor. The results will show if your cancer has gene mutations that respond to a targeted therapy. For example, a category of drugs called PARP inhibitors only treat MBC caused by a BRCA gene mutation.

Treatment

Today, there are a variety of treatment options for metastatic breast cancer. The goal is having the longest survival possible through treatment that shrinks tumors or slows their growth with the fewest possible side effects.

Typically, women with MBC receive treatment in a sequenced manner, starting with the initial treatment, referred to as first-line therapy, and then switching to a second- and even third-line therapy when the cancer progresses. It is not uncommon for women with MBC to receive several lines of therapy and to stay on one treatment for months or even years before proceeding to the next treatment option. The main categories of treatment are as follows:

• Hormone therapy
  Hormone therapy is an effective treatment for estrogen receptor-positive (ER-positive) metastatic breast cancer. The therapy works by blocking or lowering the level of estrogen from getting to cancer cells, which the cancer needs to grow. Options for hormone therapy include estrogen-blocking treatments and aromatase inhibitors (drugs that reduce the amount of estrogen made by tissues other than the ovaries by blocking the aromatase enzyme).
  
  
• Chemotherapy
Women with metastatic breast cancer usually receive one drug at a time, rather than in a combination, although occasionally a combination regimen is recommended.


• Targeted therapy
There are a variety of targeted therapies that treat four types of metastatic breast cancers, including HER2-positive MBC, hormone receptor-positive MBC, MBC with BRCA mutations and metastatic TNBC.


• Immunotherapy
One type of immunotherapy used to treat metastatic breast cancer is called a PD-L1 inhibitor because it targets the PD-L1 protein found on some tumor cells and immune cells. It is used with chemotherapy.


• Surgery
Unlike early stage breast cancer where surgery can be curative, surgery's role in MBC is mostly to slow the spread of the cancer or remove a tumor that is causing discomfort. However, surgery can be an option to treat stage 4 breast cancer that has spread to the brain. The goal is to shrink or temporarily remove the cancer in the brain. Usually, surgery of this type is done by a neurosurgeon, a specialist who operates on the head, brain and central nervous system.


• Radiation therapy
As with surgery, radiation therapy may be used to shrink or slow tumor growth and treat pain in women with stage 4 breast cancer. It also is used to treat breast cancer that has spread to the brain. Several types of radiation therapy are used to treat brain metastases based on the person's medical needs.

Clinical Trials

Many new treatment options for metastatic breast cancer are on the horizon that show great promise in increasing survival rates and improving women's quality of life. A clinical trial offers women the chance to try one of these new therapies before it is available to all patients. Here is what you need to know about taking part in a clinical trial for MBC.

Cancer Clinical Trials Explained
Cancer clinical trials — also known as cancer clinical studies — are conducted around the country to find the answers necessary to develop innovative cancer therapies. They can involve a new drug, a different way of administering treatment or a new surgical technique.

Besides spurring progress against cancer, clinical trials make it possible for patients to receive state-of-the-art cancer care from the leading experts in the field because:

• Cancer clinical trials take place in doctors' offices, clinics, cancer centers and hospitals around the country, meaning enrolled patients can get expert medical care in their own communities.
  

• Clinical trials are offered for all stages of cancer, including for newly diagnosed patients and those with metastatic disease.
  
  
• All patients who join a clinical trial are given the best cancer treatment options available or the chance to receive a new treatment being considered.
  
  
• Costs directly related to the study — the drugs used, tests, procedures and doctor visits — are covered by the sponsor of the study. While health plans may not cover all patient care costs in a study, in many cases, routine patient costs, such as extra doctor visits, are covered by the sponsor or by insurance including Medicare.

• At any time, a patient can leave a cancer clinical trial for any reason, without giving up access to other treatment.

Types of Clinical Trials

There are four phases of clinical trials:

• Phase 1 trials – These studies are usually the first that involve people and are done to find the highest dose of the new treatment that can be given safely without causing severe side effects.
  
  
• Phase 2 trials– These studies test the safety of the experimental drug in about 25 to 100 patients, examine the possible short-term side effects and risks associated with the drug and begin to evaluate how well the new drug works against a particular kind of cancer.
  
  
• Phase 3 trials – In these studies, the new drug, vaccine or a new combination of drugs is tested in a large number of patients (at least several hundred) to compare the safety and effectiveness of the therapy against the current standard treatment. Because researchers do not know yet which treatment is better, participants are often picked at random to receive one of the treatments, and neither the doctor nor the patient knows which of the treatments the patient is getting. This is known as a randomized double-blind study.
  
  
• Phase 4 trials– Often referred to as post-marketing surveillance trials, these studies often involve several thousand people and are used to further evaluate the effectiveness and long-term safety of a new drug or vaccine after the therapy has been approved by the Food and Drug Administration (FDA) and is on the market. In some cases, FDA requires phase 4 studies to assess how a new medicine affects a specific subgroup of patients.

Who Can Join a Clinical Trial?

Every clinical trial has a study plan, or protocol, that describes how the study will be conducted and the steps involved. The protocol also lists the requirements for a patient to enroll in the trial. Called eligibility criteria, these requirements include:

• Your current health status
• Your medical history
• Having a certain type and stage of cancer
• Having been treated, or not treated, with a certain kind of therapy in the past
• Having specific genetic changes in your tumor
• Being in a certain age group

How to Find a Clinical Trial

Cancer clinical trials take place across the U.S. and are sponsored by the federal government, drug companies, nonprofit organizations, hospitals and academic centers. Therefore, if you are considering a clinical trial, there are many avenues to find one that could be a good option for you.

As a start, talk to your oncologist or another member of the health care team, who may know of ongoing trials for MBC therapies. Your health care team may be able to search for a trial for you and help you decide about joining the study. In addition, there are many resources to look for clinical trials yourself:

• National Cancer Institute (NCI)
  NCI operates a free Cancer Information Service that can search available clinical trials for you and gives you a list to discuss with your oncologist. NCI also has a website listing NCI-funded clinical trials.
  
  
• National Library of Medicine
  Part of the National Institutes of Health, the National Library of Medicine hosts ClinicalTrials.gov, clinical trials for cancer including many sponsored by drug companies.
  
  
• Cancer centers and clinics
  Many cancer centers across the country sponsor or take part in clinical trials. Of these, 71 are NCI-Designated Cancer Centers, meaning they meet rigorous standards for conducting research. NCI lists these cancer centers and clinics via its NCI-Designated Cancer Centers webpage.
  
  
• Drug and biotechnology companies
  Many drug companies provide lists of the clinical trials they are conducting. The website of the Pharmaceutical Research and Manufacturers Association (PhRMA) — the association representing many drug and biotechnology manufacturers — includes a list of member companies, some of which sponsor cancer clinical trials.
  
  
• Cancer advocacy groups
  Many cancer advocacy organizations serve as an information resource to patients, including providing information about clinical trials. Generally, the websites of these organizations have lists of clinical trials or refer you to the websites of organizations that match patients to trials.

Living with Metastatic Breast Cancer

It is normal to feel anxious and scared about having metastatic breast cancer. It is also important to know that advanced breast cancer treatments can be very successful, and you can "live well" with MBC for many years.

Even though metastatic breast cancer can be an emotional roller coaster, focus on doing the things you love to do and living life in the present. Other ways to live well with MBC include eating well, exercising regularly, even if that means just taking a walk with family members or friends, and considering joining a support group for women with MBC.

This resource was created with support from Daiichi Sankyo, Merck and Sanofi Genzyme.

References

1. Mariotto AB, et al. Estimation of the Number of Women Living with Metastatic Breast Cancer in the United States. Cancer Epidemiol Biomarkers Prev. 2017;26(6):809-815.
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3. Susan G. Komen. Treatments for Metastatic Breast Cancer. Accessible at: https://ww5.komen.org/BreastCancer/RecommendedTrea....
4. Lippman ME. Chapter 74: Management summary for the care of patients with metastatic breast cancer, in Harris JR, Lippman ME, Morrow M, Osborne CK. Diseases of the Breast, 5^th edition. Lippincott Williams and Wilkins, 2014.
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6. CancerConnect. Metastatic Breast Cancer (MBC): Progress and Hope. May 22, 2020. Accessible at: https://news.cancerconnect.com/breast-cancer/metas....
7. American Society of Clinical Oncology. Breast Cancer -Metastatic: Types of Treatment. April 20, 2019. Accessible at: https://www.cancer.net/cancer-types/breast-cancer-....
8. American Cancer Society. Types and Phases of Clinical Trials. Accessible at: https://www.cancer.org/treatment/treatments-and-si....
9. National Cancer Institute. What Are Clinical Trials? Accessible at: https://www.cancer.gov/about-cancer/treatment/clin....