Hormone receptor status
Hormone receptor status is a major factor in planning treatment for breast cancer. Some breast cancer cells grow with the help of estrogen and/or progesterone (female hormones that are produced in the body). These tumor cells have special proteins, called hormone receptors, on their surface. When hormones attach to hormone receptors, the cancer cells with these receptors grow.
Breast cancers with hormone receptors are called hormone-receptor positive (or estrogen/progesterone receptor-positive) and can be treated with hormone therapies. Only cancers with hormone receptors will respond to hormone therapies like tamoxifen and the aromatase inhibitors, anastrozole (Arimidex), letrozole (Femara) and exemestane (Aromasin). Those that do not have receptors (and cannot be treated with hormone therapies) are called hormone-receptor negative (or estrogen/progesterone receptor-negative). Hormone receptor status is determined by testing the tissue removed during a biopsy.
Estrogen and progesterone receptors
Breast cancers that are estrogen receptor-positive also tend to be progesterone receptor-positive. And, cancers that are estrogen receptor-negative tend to be progesterone receptor-negative. Sometimes, a breast cancer is positive for estrogen receptors, but negative for progesterone receptors. Because current hormone therapies are designed to treat estrogen receptor-positive cancers, these cases are treated the same way as breast cancers that are positive for both hormone receptors.
How do hormone therapies work?
Hormone therapies can stop tumor growth (in hormone receptor-positive cancers) by preventing cancer cells from getting the estrogen they need to grow. They can do this in different ways. Some hormone therapies, like the drug tamoxifen, attach to the receptor on the surface of the cancer cell and block estrogen from attaching to the receptor. Other therapies, like aromatase inhibitors, lower the level of estrogen in the body so that the cancer cells cannot get the estrogen they need.
Hormone receptor status and prognosis
Hormone receptor status is also related to recurrence (the return of cancer after treatment). Hormone receptor-positive tumors have a slightly lower chance of recurrence than hormone receptor-negative tumors at five years after diagnosis. However, this difference decreases and over time, goes away [16,17].
Learn more about hormone therapies in the Treatment section.
HER2/neu (erbB2) status
HER2/neu (human epidermal growth factor receptor 2), also called ErbB2, is a protein that appears on the surface of some breast cancer cells. This protein is an important part of the pathway for cell growth and survival. HER2-positive status (also called HER2/neu over-expression) is found in about 20 percent of all breast cancers [18]. These breast cancers tend to be more aggressive and have a poorer prognosis than HER2/neu-negative cancers. However, it is not clear whether HER2/neu status is an independent risk factor for these traits. HER2/neu-positive cancers also tend to be estrogen receptor-negative and have poorly differentiated cells, both of which lead to poorer prognosis [19]. HER2/neu-positive cancers can benefit from trastuzumab (Herceptin) therapy, which directly targets the HER2/neu receptor [6]. This type of therapy is not used for cancers that are HER2-negative. On the other hand, HER2/neu-positive cancers do not respond as well to tamoxifen as HER2/neu-negative cancers do [6,26]. Therefore, knowing HER2/neu status helps guide your chemotherapy regimen. All tumors should be tested for HER2/neu status. While HER2 status is an important marker for therapy options, it is unclear at this time whether or not it is an independent predictor of prognosis or survival.
Two common ways to determine HER2/neu status in clinical practice are: 1) immunohistochemistry (IHC) testing which detects the amount of HER2/neu protein in the cancer calls and 2) fluorescence in situ hybridization (FISH) testing which detects the number of copies of the HER2/neu gene in the cancer cells.
For more information on trastuzumab (Herceptin), see the Treatment section.
Proliferation rate
How fast a tumor grows, known as its proliferation rate, can help show how aggressive a tumor is and how likely it is to spread to other parts of the body. Tumors that have a high proliferation rate (or are growing fast) often have a worse prognosis than those that have a low proliferation rate.
Proliferation rate could be a good predictor of prognosis. However, there are issues related to its measurement that lead to some variability in how much health care providers use proliferation rate in making treatment decisions.
Ki-67
The Ki-67 antibody is now the primary means for determining proliferation rate. When cells are growing and dividing (proliferating), they make a protein called a proliferation antigen. By counting the number of cells with this antigen, health care providers can determine a tumor's proliferation rate.
Cells with the proliferation antigen can be identified using the Ki-67 antibody, which attaches itself to the antigen. The more the Ki-67 antibody attaches to numerous cells on a tissue sample, the more tumor cells are likely to grow and divide rapidly. The result of this test is usually a percentage that indicates if a low, moderate or high proportion of cancer cells are in the process of dividing.
S-phase fraction
S-phase fraction was a way to determine how many cells are in the process of dividing. Although used in the past, this test is not used in current clinical practice.
Updated 10/26/09
