Understanding PIK3CA, AKT1, and PTEN in breast cancer treatment

Biomarkers are substances found in tissue, blood, or other bodily fluids that provide information about what is happening in the body. Biomarker testing is an important part of cancer diagnosis and treatment, and helps identify proteins, genes, or other substances related to a cancer’s biology.

Based on the results of biomarker testing, healthcare providers can better understand how the cancer is growing, if the cancer is aggressive, and what therapies the cancer is most likely to respond to. This helps healthcare providers tailor treatment to an individual and their diagnosis.

If you or a loved one has been diagnosed with breast cancer, having a basic understanding of different biomarkers is important to understanding treatment options.

The main biomarkers in breast cancer treatment

The starting point for biomarker testing is hormone receptor status and HER2 status. These tests are ordered for every breast cancer tumor:

Hormone receptors (HR)

Some breast cancers can use certain hormones to fuel growth and spread. HR-positive cancers feature proteins called estrogen receptors (ER) and/or progesterone receptors (PR), which attract and attach to these hormones. HR-positive cancers are often treated with hormone therapy (also called endocrine therapy), drugs that neutralize these hormones.

Human Epidermal Growth Factor Receptor 2 (HER2)

HER2 is a protein involved in the growth of normal cells. Some cancer cells have large amounts of HER2, which contributes to the growth and spread of cancer and tends to make cancer more aggressive. Cancer cells with large amounts of HER2 are said to be HER2-positive and can be treated with therapies that target and block HER2.

PIK3CA, AKT1, and PTEN mutations

A healthcare team may order other biomarker testing based on information about the cancer, such as HR status, HER2 status, and the stage of the cancer.

This can include testing for mutations to three genes important to cellular growth and division:

• PIK3CA. A gene that provides cells with instructions for making a protein called PI3K, which helps provide cells with energy to fuel growth (among other functions).
• AKT1. A gene that provides instructions for making AKT1 kinase, a protein needed to regulate cell growth, maturation, and survival. It also helps regulate the self-destruction of damaged cells.
• PTEN. A tumor suppressor gene that provides instructions for making an enzyme called PTEN. Tumor suppressor genes make substances that stop cells from dividing and triggers cells to self-destruct. They act as a control for cell division.

Keep in mind that these are simplified explanations of a complex biological process.

But the basic idea is that in some breast cancers, one or all of these genes are mutated, which causes them to behave differently than normal. This can drive the growth of cancer cells and/or remove the control that normally limits cellular growth and division.

Testing for these gene mutations can be performed as part of molecular profiling, a type of biomarker testing that uses blood samples or tumor tissue biopsies to look for acquired genetic mutations that can be driving cancer growth.

If you see these terms—or others—on a test result or medical report, ask your healthcare provider to explain what they mean.

What this can mean for breast cancer treatment

PIK3CA mutations are present in up to 40 percent of HR-positive/HER2-negative breast cancers (the most common subtype of breast cancer). These mutations are associated with worse prognosis and resistance to hormone therapy (the main treatment for HR-positive/HER2-negative breast cancer).

However, PIK3CA, AKT1, and PTEN mutations are also potential targets for cancer therapy. Targeted therapies called PI3K inhibitors and AKT inhibitors have become an important part of treatment in breast cancer. One drug, which became available in 2023, targets cancer cells with PIK3CA, AKT1, or PTEN mutations.

These drugs work by blocking the proteins or enzymes produced by the mutated genes described above. These drugs are used in combination with hormone therapy. In some cases, they are used in combination with hormone therapy plus other types of targeted therapies.

It’s important to remember that no cancer treatment is right for every person. If you have questions about a diagnosis or treatment options, your best source of information will be your healthcare team.