Molecular subtypes of breast cancer

Every breast cancer is highly individual, and as you go through the diagnosis process, you’ll learn about characteristics of the breast cancer cells that help you and your care team develop your treatment plan. Along the way, you may hear your doctors or others use the term molecular subtype.

All cells are made of molecules, and features of these molecules determine what a cell does in the body. Molecular subtype is a term that describes how breast cancer cells behave based on their characteristics, including:

• Genetic mutations
• Proteins
• Hormone receptors
• Grade (how different the breast cancer cells look from normal breast cells)
• How fast the cells grow
• In some cases, the Ki-67 score, a measure of a protein that shows how fast cells are multiplying

Right now, molecular subtypes are defined for invasive, stage I-IV, breast cancers. Molecular subtyping is not typically done in ductal carcinoma in situ (DCIS), or stage 0 breast cancer.

Tests that look at molecular subtype include BluePrint and Prosigna, and they test breast cancers that are stage I or II. Doctors can also sometimes predict the molecular subtype based on the characteristics of the cancer.

Why are molecular subtypes used in breast cancer?

Molecular subtype plays an important role in research. It allows doctors and researchers to classify different breast cancers by their receptor status, grade, and behavior. Using molecular subtypes in research has helped in developing new treatments and in understanding how different types of breast cancers might respond to them.

It’s important to know that the molecular subtype of breast cancer does not determine the specific treatments that your doctor might recommend for you. Instead of the molecular subtype as a whole, your doctors will choose treatments by looking at the characteristics of the cancer cells that make up the molecular subtype. For example, if the breast cancer is hormone receptor-positive, your doctor will likely recommend endocrine therapy. It is each characteristic of a molecular subtype, such as hormone receptor status, that informs treatment decisions — not the molecular subtype itself.

Because the breast cancer’s molecular subtype is not part of treatment decision making, you may not be told the breast cancer’s molecular subtype. It is not recorded in your pathology report. It’s OK if you don’t know it, and you do not need to know it to get the best treatment possible.

There are many test results that do guide treatment decisions. Your pathology report will contain these kinds of test results, including hormone receptor status, HER2 status, tumor grade, and others. There are also other tests that guide treatment decisions, such as genomic tests that look at gene activity in breast cancer cells.

Some genomic tests may involve molecular subtyping, but the molecular subtyping does not guide treatment decisions. There are no US breast cancer treatment guidelines that recommend molecular subtype testing as a way to determine treatment choices.

Still, you may see molecular subtypes discussed in online research, or hear health professionals or others mention them. Below, we’ll explain the four main categories.

The four main molecular subtypes of breast cancer

There are four broad molecular subtypes of breast cancer. These classifications are called “broad” because they can change over time as new research emerges.

Luminal A

Luminal A breast cancers:

• Are estrogen receptor-positive, progesterone receptor-positive, or both
• Are HER2-negative
• Have low Ki-67 (less than 20% positive)
• Are slow-growing
• Are low-grade

Sixty-eight percent of all breast cancers are Luminal A.
Because Luminal A tumors are hormone receptor (ER and/or PR)-positive, they respond best to treatments that target the activity of these hormones. Treatments for hormone receptor-positive breast cancer can include surgery, endocrine therapy, targeted therapy, radiation therapy, and chemotherapy.

Luminal B

Luminal B breast cancers:

• Are estrogen receptor-positive, and can be either progesterone receptor-positive or negative
• Can be either HER2-positive or HER2-negative
• Have a high Ki-67 (more than 20% positive)
• Are faster-growing than Luminal A tumors
• Are higher grade

Ten percent of all breast cancers are Luminal B.

Luminal B tumors that are hormone receptor-positive, but HER2-negative, respond best to treatments that target estrogen and progesterone activity. These can include surgery, endocrine therapy, targeted therapy, radiation therapy, and chemotherapy.

Luminal B tumors that are hormone receptor-positive and HER2-positive, sometimes called triple-positive breast cancer, are treated with medicines that target HER2 receptors, such as trastuzumab, as well as surgery, radiation therapy, chemotherapy, and endocrine therapies.

Basal-like/triple-negative

Basal-like breast cancers:

• Are estrogen receptor-negative, progesterone receptor-negative, and HER2-negative

Ten percent of all breast cancers are basal-like, though this number rises to 20% among African-American women.

Young women and women with inherited BRCA1 mutations who are diagnosed with breast cancer are also more likely to have basal-like breast cancer.

Because basal-like tumors are negative for estrogen and progesterone receptors, and negative for HER2 receptors, these cancers are called triple-negative. Triple-negative breast cancers may be treated with surgery, chemotherapy, immunotherapy, and targeted therapies.

HER2-enriched/HER2-positive

HER2-enriched breast cancers:

• Are HER2-positive
• Are estrogen and progesterone receptor-negative
• Are faster-growing than luminal subtypes

Fifteen to 20% of all breast cancers are HER2-enriched.

Because HER2-enriched breast cancers have HER2 protein overexpression, they respond best to treatments that target the HER2 protein. HER2-positive breast cancers may be treated with surgery, radiation therapy, HER2-targeted therapy, and chemotherapy.

Molecular subtype testing

Some companies offer molecular subtype testing. Two such tests are BluePrint and Prosigna. These tests look at tumor tissue characteristics to identify the molecular subtype. You can read more about these tests on the Genomic testing page.

Because molecular subtype testing is not part of the standard breast cancer diagnosis process, your doctor may not recommend it for you. If your doctor does suggest molecular subtype testing, it’s OK to ask what role the results will play in your care.

BluePrint and Prosigna are covered by many health insurance plans, as well as Medicare, but your individual plan will determine how much insurance pays and how much you may need to pay out-of-pocket. Visit our Financial assistance section for information about ways to cover the cost of care.