Triple-Negative Breast Cancer: Definition

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Triple-negative breast cancer is breast cancer that tests negative for three proteins: ER, PR, and HER2. It makes up about 10% to 15% of all breast cancers. The name describes test results, not a specific cancer type.

Pathologists test every invasive breast cancer for these three proteins. The results guide treatment. This article explains how pathologists decide that a cancer is triple-negative, how it behaves, how doctors treat it, and what your report may say.

What does triple-negative mean?

Triple-negative means the cancer tested negative for ER, PR, and HER2. ER is the estrogen receptor, and PR is the progesterone receptor. These proteins matter because some treatments target them. Hormone therapy works on cancers that make ER or PR. HER2-targeted drugs work on cancers that make too much HER2. A triple-negative cancer does not respond to these treatments, so doctors use other options.

Triple-negative is not a diagnosis on its own. The diagnosis is the type of breast cancer, such as invasive ductal carcinoma. Triple-negative describes the test results for that cancer.

How do pathologists decide that a cancer is triple-negative?

The pathologist tests a cancer sample with immunohistochemistry. This test uses antibodies to show which proteins the cells make. A cancer is triple-negative when all three results are negative:

ER negative. Fewer than 1% of the cancer cells stain for the estrogen receptor.
PR negative. Fewer than 1% of the cancer cells stain for the progesterone receptor.
HER2 negative. The HER2 score is 0 or 1+. A score of 2+ counts as negative only when a second test, called ISH, shows no extra copies of the HER2 gene.

Some cancers show ER staining in 1% to 10% of cells. Pathologists report these as ER low positive. By definition, these cancers are not triple-negative. However, they often behave more like ER-negative cancers. Your oncologist will consider this when planning treatment.

Can a triple-negative cancer also be HER2-low?

A triple-negative cancer can also be HER2-low. HER2-low means a HER2 score of 1+, or 2+ with a negative ISH test. These cancers are still HER2-negative. They make a small amount of HER2, however. For HER2-low cancers that have spread and grown after other treatment, a drug called trastuzumab deruxtecan may be an option. See HER2 in breast cancer.

Which types of breast cancer can be triple-negative?

Many types of invasive breast cancer can be triple-negative. Common examples include:

Invasive ductal carcinoma. This is the most common type of breast cancer. It is also called invasive carcinoma of no special type.
Metaplastic carcinoma. Metaplastic carcinoma is a rare type that can be triple-negative.
Adenoid cystic carcinoma. Adenoid cystic carcinoma of the breast is usually triple-negative. Unlike most triple-negative cancers, it carries a favorable outlook.

Who gets triple-negative breast cancer?

Triple-negative breast cancer can affect anyone with breast cancer. It is more common in these groups:

Younger women. It is more common in women who have not gone through menopause.
African American women. It occurs more often in African American women.
People with a BRCA1 mutation. An inherited change in the BRCA1 gene is strongly linked to triple-negative cancer.

Guidelines recommend genetic testing for anyone with triple-negative breast cancer, at any age. See BRCA1 and BRCA2 in breast cancer.

How does triple-negative breast cancer behave?

Triple-negative breast cancer tends to grow and spread faster than most other breast cancers. It is more likely to have spread by the time doctors find it.

The outlook depends mostly on the stage. The American Cancer Society reports these 5-year relative survival rates for women diagnosed from 2015 to 2021:

Localized. 92% when the cancer has not spread outside the breast.
Regional. 67% when it has spread to nearby lymph nodes or tissues.
Distant. 15% when it has spread to distant organs.

These numbers describe large groups of people treated years ago. They may underestimate outcomes with current treatment. They cannot predict what will happen to one person.

How do doctors treat triple-negative breast cancer?

Treatment depends on the cancer stage and your overall health. Your oncologist chooses the plan. The main options include:

Surgery and radiation. Surgery removes the cancer. Radiation is often added for early-stage cancer.
Chemotherapy. Chemotherapy is the main drug treatment. Doctors often give it before surgery to shrink the tumor.
Immunotherapy. Doctors may add pembrolizumab, an immunotherapy drug, to chemotherapy. In higher-risk early cancer, the stage decides who receives it. In advanced cancer, a PD-L1 test decides.
Targeted treatment. PARP inhibitors, such as olaparib, may help people with a BRCA mutation. Antibody-based drugs may be options for cancer that has spread.

What else might my report describe?

Your report may include other findings that help your doctors plan treatment:

Grade. How abnormal the cancer cells look. See grade.
Ki-67. How many cancer cells are dividing. See Ki-67.
Tumor-infiltrating lymphocytes. Immune cells inside the tumor. See tumor-infiltrating lymphocytes.
Residual cancer burden. After chemotherapy before surgery, the report may describe how much cancer remains. See residual cancer burden.

What might my report say about triple-negative status?

Reports describe the three results in a few standard ways. Each laboratory phrases them a little differently:

ER negative and PR negative. The report may give the percentage of stained cells, such as 0% or less than 1%.
HER2 negative. The report gives the HER2 score, such as 0 or 1+. A 2+ result also lists the ISH result.
Triple-negative. Some reports state this summary directly. Others list only the three results.
ER low positive. ER staining in 1% to 10% of cells. The cancer is not triple-negative, but it may behave like one.

Questions to ask your doctor

Is my breast cancer triple-negative?
What were my exact ER, PR, and HER2 results?
Is my cancer HER2-low or ER low-positive?
What type and grade of breast cancer do I have?
What stage is my cancer?
Should I have genetic testing for BRCA1 and BRCA2?
Will I have chemotherapy before surgery?
Am I a candidate for immunotherapy or a clinical trial?
How will you check my response to treatment?