Metastatic breast cancer (MBC) refers to breast cancer that has spread beyond the breasts and nearby lymph nodes to other organs in the body. MBC is also known as advanced or stage 4 cancer.

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MBC can develop after an initial diagnosis of earlier stage breast cancer. It is also possible for MBC to be a person’s first diagnosis.

There is currently no cure for MBC, but there are many treatment options available that can slow the cancer’s growth.

This article explores the role that genes play in the development of MBC and how genetic testing is leading researchers to newer targeted treatments.

Mutations in genes can affect a person’s susceptibility to breast cancer. Specifically, two categories of mutations — germline mutations and somatic mutations — may increase an individual’s risk of developing breast cancer.

Germline mutations are present in every cell of the body. These mutations run in families, and a person may inherit them from a parent. About 5–10% of breast cancer cases develop because a person has a hereditary predisposition to breast cancer.

On the other hand, somatic mutations are changes that develop after birth. These changes occur in a single cell and in any cells that derive from that single cell if it divides. A person cannot inherit somatic mutations.

Some specific germline and somatic gene mutations may increase a person’s risk of developing breast cancer that progresses to MBC.

“We know about several germline mutations, like BRCA1 and BRCA2, that increase our risk [of] cancer. Often, the cancers that these mutations cause are more aggressive, so are at higher risk of metastasizing,” explained Dr. Natasha B. Hunter, a board certified oncologist at Seattle Cancer Care Alliance in Washington.

“We also know that tumors develop somatic mutations, some of which can increase their ability to evade immune detection or make them resistant to therapies,” Dr. Hunter added.

Genetic testing does not yet play a role in the diagnosis or detection of MBC.

A doctor diagnoses MBC the same way they do other stages of breast cancer — with laboratory tests, imaging tests, and biopsies.

However, research is ongoing into how genetic testing can help oncologists catch breast cancer just as it starts to spread beyond the affected breast.

“We don’t use genetic testing for the diagnosis or detection of MBC currently,” said Dr. Hunter, “but we hope that at some point we may be able to use highly sensitive detection methods that use DNA or other substances in the blood to detect early metastatic disease so that we could intervene and treat before the development of incurable MBC.”

Genetic testing is useful for determining a person’s risk of developing breast cancer in the first place.

“There are strict criteria set forth by the National Comprehensive Cancer Network (NCCN) for breast cancer genetic testing, and they are generally the criteria the insurance companies use to establish testing guidelines,” explained Dr. Susan Klugman.

Dr. Klugman is the director of reproductive and medical genetics with the Montefiore Health System and a professor at the Albert Einstein College of Medicine, both in New York City, NY.

The NCCN indicates genetic testing when a person:

  • has a blood relative with a variant in an implicated gene that is known or likely to cause breast cancer
  • has a personal history of breast cancer and meets other sub-criteria, including age, previous cancer diagnosis, and ethnicity
  • has a first or second degree blood relative who meets any of the criteria above
  • does not meet any of the other criteria but has a higher-than-6% chance of having a BRCA1 or BRCA2 cancer-causing gene mutation based on probability models

The NCCN also states that doctors may consider genetic testing when a person has had multiple primary breast cancers and first received a diagnosis between the ages of 50 and 65 years.

They may also consider genetic testing when a person does not meet any of the other criteria but has a 2.5% to 5% chance of having a BRCA1 or BRCA2 cancer-causing gene mutation based on probability models.

“[Individuals] found to have mutations or changes in certain genes — pathogenic variants — can opt for surveillance and medical therapy or prophylactic surgery prior to the onset of cancer,” Dr. Klugman told Medical News Today.

The results of genetic testing can be valuable to family members as well.

“Relatives who are of reproductive age [who] are planning to have a family, and have a genetic mutation, could consider preimplantation genetic testing after in vitro fertilization to avoid passing down the genetic mutation to offspring,” Dr. Klugman added.

Standard treatments for MBC are drug therapies such as chemotherapy, immunotherapy, hormone therapy, and targeted drugs. Sometimes, doctors use a combination of these therapies. In other situations, a person may need to undergo surgery or radiation therapy.

The results of genetic testing influence treatment plans for MBC. Certain mutations make a person eligible to receive particular therapies. The detection of genetic mutations can help doctors design more tailored and effective treatment plans.

“The tumors of patients with germline BRCA mutations can be particularly responsive to PARP inhibitors, which take advantage of the DNA repair issues that the BRCA mutation causes,” said Dr. Hunter.

“Patients with certain mutations in the tumor itself (somatic mutations) can also receive targeted therapies. For instance, patients whose tumors harbor PIK3CA mutations can receive a medication called alpelisib,” Dr. Hunter added.

Genetic testing results can also qualify individuals for clinical trials in which they can access newer treatment options that they would not typically have access to in traditional clinical settings.

Current treatments for MBC can help slow the growth of tumors, improve symptoms, and extend survival, but the condition remains incurable. However, ongoing research into genetics may hold the key to a brighter outlook.

“I think we are only seeing the tip of the iceberg in terms of our understanding of genetics, gene expression, and other molecular-level interactions in breast cancer,” Dr. Hunter told MNT.

“Right now,” added Dr. Hunter, “I think we’re seeing the most potential in continuous monitoring to detect early metastatic disease so that we could intervene and treat before the development of incurable MBC — holding the potential for cure with early detection. But I think there’s much more that’s exciting on the horizon.”