Causes of Metastatic Breast Cancer

Metastatic breast cancer (also called stage 4 breast cancer) is breast cancer that has spread to another part of the body, most commonly the liver, brain, bones, or lungs. Metastasis occurs when cancer cells separate from the original tumor, enter the blood or lymphatic channels (a large network of vessels in the body), and spread to the lymph nodes or other tissues or organs of the body.

When breast cancer spreads to an area adjacent to the original tumor (such as the lymph nodes located under the armpits) it’s not considered metastasized. Rather, it’s called “locally advanced breast cancer.” But if the cancer spreads to organs or tissues located far away, it is referred to as metastasized. When breast cancer spreads to two or more areas of the body, it’s referred to as stage 4 breast cancer or metastatic breast cancer.

Even after a person with breast cancer is in remission, breast cancer can return and may metastasize to other parts of the body. This can occur months or even years after a person is initially diagnosed. In fact, nearly 30% of people who are diagnosed with early-stage breast cancer will eventually develop metastatic cancer.

Researchers have done extensive studies on the process of metastasis but have not yet been able to predict how long inactive cancer cells can stay in the body before they begin to metastasize.

But what causes cancer to spread? Can it be stopped or slowed by implementing diet, lifestyle, or other changes? What does the research say?

Common Causes

Most metastatic breast cancers are caused by breast cancer cells that remained in the body and survived after initial breast cancer treatment was complete. Although the purpose of modern cancer therapies is to treat cancer cells systemically (throughout the entire body) and stop the cancer cells from traveling to distant organs, in some instances, the cells escape the treatment, metastasizing later on. 

Often, this process occurs many years after the person has completed treatment for locally advanced breast cancer. This is sometimes referred to as distance recurrence.

With distance recurrence, the breast cancer cells have remained in the body as dormant cells for months or, many times, for years. Something occurs that triggers the dormant cells to become cancer cells again, but it is not well understood just why this occurs.

Note, although in metastatic breast cancer, the cancer has spread to other parts of the body, the cancerous cells are still breast cancer cells and are treated as such (as far as medical intervention goes). For example, when breast cancer spreads to the bone, it is not considered bone cancer and is therefore treated differently. Rather, it’s treated with breast cancer drugs.

Risk of Metastasis

Although researchers have not yet been able to identify a direct cause of breast cancer metastasis, there are several factors linked to the cause of metastasis. The risk of metastasis can vary from one person to another, depending on several factors, including:

• The characteristics of the cancer cells (referred to as the biology, or subtype, of the cells), including hormone receptor status and human epidermal growth factor receptor 2 (HER2) status, both of which are labeled as either positive or negative
• The stage at the time of the original diagnosis (earlier stages result in a lower risk for metastasis)
• The treatments received when breast cancer was originally diagnosed (the more effective the treatment, the less likely metastasis is expected to occur).

Studies

According to a 2013 study published in the Journal of Internal Medicine, breast cancer is the most frequently diagnosed cancer and the leading cause of death from cancer in women worldwide. In most instances, death from breast cancer is caused by metastatic disease.

Although researchers have found new methods of identifying and treating the subtypes of the primary tumor, finding the underlying cause and treating metastasis systemically is less effective. The study suggests that “a tumor may both alter and respond to the host systemic environment [affecting most of the body’s systems instead of just a local area] in order to facilitate and sustain disease progression."

A 2016 study suggests that some subtypes of breast cancer may orchestrate metastasis by recruiting and activating stem cells. This type of research is very new and most of the data available involve animal studies because of a lack of research on human study subjects. In uncovering a potential new cause of metastasis, this research could revolutionize future breast cancer treatments, such as stem cell therapy.

Genetics

Recent studies have shown that having an inherited susceptibility to breast cancer not only has an impact on the primary tumor development in breast cancer, but it also influences the growth and progression of the cancer as well as metastasis.

Certain genes function to suppress metastasis, which include:

• NM23
• KISS1
• BRMS1
• MKK4

Other genes are involved in promoting cancer metastasis, such as:

• HER2
• MMP1
• EREG
• COX2

HER2 Status and Genetics

Human epidermal growth factor receptor 2 (HER2) is a gene that promotes cancer metastasis. The HER2 gene is a mutation, and it is not inherited. HER2 is a protein that promotes cancer cell growth because acts as a fertilizer, helping the cancer cells to rapidly reproduce. Approximately 20%–30% of women with breast cancer have extra copies of this protein.

Having extra HER2 enables a person’s breast cancer to be classified as HER2 positive. The primary significance of this is that a specific type of drug can work to block the HER2 receptor in the body. Therefore, knowing the HER2 status can guide therapeutic choices.

Hormone Receptor Status and Genetics

Another subtype of breast cancer cells is known by its hormone receptor status. For example, breast cancer cells have specific proteins that are estrogen or progesterone receptors. What this means is that when the hormones (estrogen or progesterone) attach to the receptors, they fuel cancer cell growth and can contribute to metastasis. 

Certain genes (such as FGFR2 and TNRC9) have been found to have a strong link with hormone receptor status. Studies show that common genetic variants can influence the subtype of breast cancer.

Metastasis and Genetics

When breast cancer cells spread to different parts of the body (such as the liver) they are still considered breast cancer cells and not liver cancer cells. When examined under a microscope, the metastasized cells—growing at a different site—appear similar to the cells from the primary tumor in the breast. The mutations present in breast cancer cells, from the primary tumor and breast cancer metastatic cells may be similar but may not necessarily be identical.

Lifestyle Risk Factors

The risk of metastatic breast cancer is not well understood by scientists today, and unlike breast cancer—which has extensive research data about lifestyle and other risk factors—metastatic breast cancer risks are not well known.

Lifestyle factors such as being overweight or obese, having more than one to two alcoholic drinks per day, and being physically inactive are associated with a higher risk of recurrence of breast cancer.

Although research data are available on the risks of various types of breast cancer (such as subtypes) metastasizing, researchers continue to gather evidence to find out just why metastatic breast cancer occurs and how to prevent, slow, or end the growth of metastatic cells.

A Word From Verywell

Learning that your cancer has metastasized may result in many questions, such as how this could happen. Although there aren’t many answers to this question today, it’s important to keep in mind that having to accept and live with a disease in which the cause is relatively unknown may be difficult for most people.

Make sure to talk to your healthcare team about your questions, frustrations, fears, and concerns. Although it's normal to fear the future and possible treatment-related side effects, your healthcare team is on board to do whatever it takes to relieve side effects and support your emotional needs. This is the part of treatment that is called palliative, or supportive, care, and it’s a vital aspect of the treatment plan for anyone with cancer, particularly for those with metastatic breast cancer.

This may be the most important time ever to reach out and get involved in a cancer support group, or other type of support group, whether it's an in person meeting or involves online support.