When a breast mass is diagnosed as cancerous, a sample (biopsy) of the tumor is taken and a pathologist examines its characteristics. The pathologist will determine the status of three breast cancer specific markers, the estrogen receptor (ER), progesterone receptor (PR), and a form of the epidermal growth factor receptor (HER2). These are important proteins in the design of treatment plans for breast cancers.
Triple negative (TN) breast cancer is an aggressive subtype of breast cancer that accounts for 10-15% of breast cancer cases.(1)(2)(3)The term "triple negative" describes tumors that do not produce significant amounts of any of the proteins listed above; TN tumors are ER minus (ER-), PR minus (PR-), and HER2 minus (HER2-). In the U.S. TN breast cancer occurs more often (>10%) in African American women than in non-African American women(1)(4). The reasons for the differences in TN breast cancer occurrence in different populations is not yet clear but is an active area of research.
Estrogen Receptor (ER) and Progesterone Receptor (PR)
ER and PR are proteins that bind the female sex hormones estrogen and progesterone, respectively. These hormones are produced by the ovaries and play a major role in stimulating cell division in breast cells. Estrogen and progesterone bind to their respective receptors and directly stimulate genes that regulate cell division. Breast tumor cells with a positive (+) hormone receptor status have high levels of ER and PR, possibly resulting in a faster growing tumor. These types of breast cancer can be treated with hormone therapy. Triple negative breast tumors do not have high levels of these hormone receptors. Learn more about hormonal cancer treatments.
Human Epidermal Growth Factor Receptor 2 (HER2)
HER2 is a receptor protein located on the surface of breast cells. This protein binds growth factors and stimulates cell growth and division. Breast tumor cells with a positive (+) HER2 status have high levels of HER2 on their surface. This may result in an increased ability to grow and spread. These types of breast cancer can be treated with a type of targeted therapy. Triple negative breast tumors have low levels of HER2.
In theory triple negative tumors should have a better prognosis than tumors expressing ER, PR, or HER2, because they are not receiving the growth signals provided by these proteins, but this is not the case. Breast cancers expressing ER, PR, or HER2 can be treated with drugs that inhibit the function of the receptors (i.e. Herceptin®, tamoxifen). The triple negative subtype of breast cancer is unresponsive to the available targeted treatments and currently no specific treatment guideline exists for this tumor type(1). Studies have shown that triple negative tumor cells may be more aggressive than other breast cancer subtypes, but the reasons for this are unknown (5). The lack of treatment options and aggressive nature of the tumor cells make triple negative breast cancer more difficult to treat.
Characteristics of triple negative breast cancer cells(5)(6)(3):
Triple negative breast cancers tend to share additional features that can impact tumor growth or treatment. Some of these are described below:
The shape and size of the nucleus of a cancer cell provides an indication of how abnormal the cell is likely to behave. TN tumors are more likely to be 'high grade', indicating more severe abnormalities.
This is a measure of how rapidly the cells in the tumor are dividing. It is determined by calculating the ratio of cells dividing to cells not dividing (in the viewed samples).
A higher mitotic index may indicate a more rapidly growing tumor. TN tumors often have a high mitotic index.
This describes whether or not the cancer cells 'look' like normal cells from the tissue of origin. As an example, Liver cells have specific functions and therefore do not look like breast cells. Cancer cells often lack the structure and function of the normal cells from which they arise. TN cancer cells are often 'poorly differentiated' which means they no longer look/function like normal breast cells.
Characteristics of triple negative breast cancers(3)(6)(5):
Age at Diagnosis
TN patients are often diagnosed at a slightly younger age than other breast cancer patients (average age at diagnosis: 53 vs 57.7 yrs)
TN tumors tend to be larger when the cancer is detected than other breast cancer
(3.0 cm vs 2.1cm)
TN tumors more likely to be grade III than other breast cancer subtypes (66% vs 28%)
Node Positivity (regional metastasis) lymph nodes near the tumor are more likely to test positive for the spread of cancer in TN breast cancer patients than other subtypes (54.6% vs 45.6%)
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Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of Estrogen Receptor (ER)-Negative, Progesterone Receptor (PR)-Negative, and HER2-Negative Invasive Breast Cancer, the so-called Triple-Negative Phenotype. Cancer. 2007; 109:1721-1728. [PUBMED]