This page was reviewed under our medical and editorial policy by
Daniel Liu, MD, Plastic and Reconstructive Surgeon
This page was reviewed on February 18, 2022.
Breast cancer research has uncovered more and more about the different types of breast cancer cells, based on factors involved in tumor growth. Different breast cancers behave and grow in different ways. This has led to defining breast cancer at the molecular, or smallest-cell, level.
Molecular classification of breast cancer refers to the type of cancer cells present, and to the pattern and behavior these cells display. A deeper understanding of the various subtypes of breast cancer has enabled scientists to develop breast cancer targeted treatments—and knowledge around which cancer type responds to which treatments for improved outcomes.
Breast cancer has four primary molecular subtypes, defined in large part by hormone receptors (HR) and other types of proteins involved (or not involved) in each cancer:
A fifth subtype, known as normal-like breast cancer, closely resembles luminal A.
In the United States, luminal A accounts for 73 percent of breast cancer cases, luminal B for 11 percent, triple negative for 12 percent and HER2-enriched for about 4 percent, according to the American Cancer Society.
Luminal A tumors, the most common molecular type, tend to grow at a slower rate than other cancer types. These are called HR-positive because they’re defined by their hormone receptors, specifically as estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive. A cancer that is ER- and/or PR-positive grows from estrogen and/or progesterone. Drugs that lower the amount of these hormones tend to be useful in treating this type of breast cancer.
Luminal A cancers are also described as HER2-negative. HER2 stands for human epidermal growth factor receptor-2, which is a protein normally produced by the body. From a gene perspective, HER2 plays an important role in cell growth and repair in healthy breast cells. A breast cancer patient with a normal amount of the HER2 protein has HER2-negative cancer.
Luminal B breast cancer cells tend to grow faster than the luminal A type and are considered more aggressive. They are positive for hormone receptors and for a higher-than-normal amount of HER2, so they’re both HR-positive and HER2-positive.
What is triple-negative breast cancer? In this type of cancer, the cells do not contain receptors for estrogen, progesterone or HER2. This type of breast cancer is usually invasive and usually begins in the breast ducts.
Healthy breast cells contain receptors for the hormones estrogen and progesterone. They also contain receptors for a protein called HER2, which stimulates normal cell growth. About two out of three women with breast cancer have cells that contain receptors for estrogen and progesterone, and about 20 percent to 30 percent of breast cancers have too many HER2 receptors.
Breast cancer that is estrogen receptor (ER)- and progesterone receptor (PR)-positive can be treated with hormone therapy. Breast cancer with excess amounts of HER2 can be treated with anti-HER2 targeted therapy drugs such as trastuzumab.
In women with triple-negative breast cancer, the malignant cells do not contain receptors for estrogen, progesterone or HER2. Breast cancer that is ER-, PR- and HER2-negative cannot be treated with hormone therapy or medications that work by blocking HER2, such as trastuzumab. Fortunately, triple-negative breast cancer can be treated with other options, such as chemotherapy, radiation therapy and non-HER2 targeted therapy.
What is HER2-positive breast cancer? One in five invasive breast cancers is HER2-positive, making this one of the more common breast cancer subtypes in the United States. HER2-positive cancers are ER- and PR-negative and human epidermal growth factor receptor 2 (HER2)-positive.
HER2-positive breast cancer cells carry too many copies of the HER2 gene, which makes HER2-protein receptors, found on breast cells. When they work normally, HER2 receptors control how a healthy breast cell grows, divides and repairs itself. When they proliferate, the receptors tell the cells to divide and grow rapidly and without control. That’s because their cells absorb too much of a substance called human epidermal growth factor 2, which energizes cell growth. Doctors often test breast cancer tissue for excess HER2-positive genes to determine whether the patient may benefit from targeted therapy options, which are designed to block HER2 from energizing cancer cell growth.
Symptoms of HER2-positive breast cancer are similar to those of other breast cancer types. They include a lump in the breast, changes to the breast’s shape, pain, swelling and abnormal discharge.
Depending on the cancer’s stage, treatment options for HER2-positive breast cancer may include a combination of breast cancer surgery, radiation therapy, chemotherapy and/or administration of a targeted therapy such as the immune monoclonal antibody, trastuzumab (Herceptin®).
Infiltrating breast cancer, also called invasive breast cancer, is one that has spread from its original location in the breast to other parts of the body. The most common type is infiltrating ductal carcinoma, which begins in the lining of the milk ducts. Another type is lobular carcinoma, which begins in the milk glands. Invasive ductal carcinoma and lobular carcinoma may be categorized as any of the four molecular subtypes.
About 85 percent of breast cancers are ductal carcinomas, while 11.4 percent are lobular carcinomas, according to a study published in the Annals of Medicine and Surgery. More than three-quarters of lobular carcinomas fall into the luminal A and triple-negative tumor category.
Breast cancer treatment depends on a variety of factors, including the type of breast cancer, the tumor’s size, its spread, any pre-existing conditions and your treatment preferences. Molecular subtype is taken into account as well, because a cancer fueled by specific hormones or other proteins may have better outcomes when treated with targeted options, which may include hormone therapy, which is also referred to as endocrine therapy.
Some patients, particularly those at high risk for infiltrating breast cancer, may undergo adjuvant chemotherapy after the initial treatment, which is often surgery. Adjuvant means it’s given in addition to the primary treatment.
Below are some of the most common ways of treating each molecular type of breast cancer.
Because luminal A breast cancers are HR-positive, patients who undergo surgery to remove a tumor may receive hormonal therapies to block hormones from fueling cancer growth.
Tumors in the luminal B group are often treated with chemotherapy and therapies that target the HER2 protein.
If the cancer hasn’t spread, surgery is often the first treatment option. The care team may also suggest chemotherapy, and sometimes breast cancer radiation therapy. For advanced breast cancers, treatment options include PARP inhibitors, platinum chemotherapy or immunotherapy. Hormone therapy generally wouldn’t apply for this type of cancer, because these cancer cells aren’t reactive to estrogen, progesterone or HER2.
Targeting the HER2 protein fueling this type of breast cancer may help slow it down. Monoclonal antibodies are synthetic proteins designed to attack and target HER2 cells, stopping their growth. Doctors may prescribe these drugs alone or give them in combination with chemotherapy. It’s also possible to treat this type of breast cancer with an antibody-drug conjugate via a treatment that delivers precision-focused chemotherapy to the cancer cells your care team seeks to target.
Understanding molecular types, and why they’re important to your cancer, is vital. Ask your care team to clearly explain what your molecular type means and how it impacts your health.
It may also be helpful to speak with other breast cancer patients. Connect through a support group, online forum or at your treatment center. Just remember that everyone’s breast cancer experience is different, and your treatment may be different from someone else’s, even if that person has the same molecular type as yours.
As with all aspects of your care, get as much information as possible to make informed choices about your treatment.