A biopsy examination of the suspected tumor helps the pathologists to look for typical cancerous characteristics. Microscopic examination showing uncontrolled division of cells is diagnosed as cancerous. The pathologist will look for 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 significant proteins in the design of treatment regimens for breast cancers.

Triple negative (TN) breast cancer is an aggressive subtype of breast cancer that accounts for 10-15% of breast cancer cases. 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-). The reasons for the differences in TN breast cancer occurrence in different populations is not yet clear but is a dynamic area of research.

Receptor Status

Estrogen Receptor (ER) and Progesterone Receptor (PR)

Female sex hormones estrogen and progesterone bind to ER and PR, respectively. These hormones are produced by the ovaries and contribute majorly 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 showing positive (+) hormone receptor status have high levels of ER and PR, probably resulting in a faster growing tumor. These types of breast cancers are treated with hormone therapy. However, TN breast tumors do not have high levels of these hormone receptors.

Human Epidermal Growth Factor Receptor 2 (HER2)

HER2 is a receptor protein located on the surface of breast cells. Growth factors bind to these receptors and stimulate 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 of cells to grow and spread. These types of breast cancer can be treated with a type of targeted therapy using monoclonal antibodies like Trastuzumab. TN breast tumors have low levels of HER2.

Prognosis

Theoretically, TN 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 TN subtype of breast cancer shows no responsive to the available targeted treatments and currently no specific treatment guideline exists for this tumor type. Studies have shown that TN tumor cells may be more belligerent than other breast cancer subtypes, but the reasons for this are unknown. Treatment unavailability and aggressive nature of the tumor cells make TN breast cancer more difficult to treat.

Characteristics of TN breast cancer cells

TN breast cancers tend to share additional features that can impact tumor growth or treatment. Some of these characteristics are described below:

Nuclear Grade

The shape and size of the nucleus of a cancer cell provides an indication of how an abnormal cell is likely to behave. TN tumors are more likely to be 'high grade', indicating more severe abnormalities.

Mitotic Index

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 possibly indicate a more rapidly growing tumor. TN tumors often have a high mitotic index.

Differentiation State

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 TN breast cancers Age at Diagnosis

TN patients are often diagnosed at a younger age than other breast cancer patients (average age at diagnosis: 53 to

57.7 years of age)

Tumor Size

TN tumors tend to be larger when the cancer is detected than other breast cancer (2.1 cm to 3 cm)

Tumor Grade

TN tumors more likely to be grade III than other breast cancer subtypes (28% to 66%)

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 (45.6% to 54.6%)

Line of treatment

There is a general trend of treating a cancerous condition which is to be followed in curing ER+, PR+ and HER2+ diagnosed cancers.

1. Mastectomy (surgical removal of the affected breast) or lumpectomy (surgical removal of the affected part of a breast)
2. Chemotherapy

• Radiation

But treatment of TN breast cancer requires a special line of treatment. The steps are as follows-

1. Chemotherapy
2. Surgical removal

• Radiation

By far, the medical arena lacks drugs which specifically targets ER-, PR-, and HER2- tumors. Pharmacologists and scientists are working on the discovery of drugs which can successfully decrease the malignancy and thereby reduce the risk of fatality of TN breast cancer patients. The existing anticancer drugs are not effective per se on this form of breast cancer.

Tags: MET Institute of Pharmacy