Hormone receptors are proteins on the surface of all cells, including normal breast cells and some breast cancer cells, that help to mediate how hormones such as estrogen interact with cells; they may also stimulate cell growth.
Breast cancer cells can overexpress (be positive for) either estrogen receptors (ER+), progesterone receptors (PR+), or both. Hormone receptor positive tumors can occur over several years after an initial diagnosis.
How is hormone receptor–positive breast cancer diagnosed?
A pathologist will test the breast cancer cells for estrogen or progesterone receptors using special stains on the tumor specimen called immunohistochemistry or IHC. One type of multigene test, the Oncotype DX, may also provide information about the hormone receptor status by measuring the RNA (genetic material in the tumor) that codes for the development of these receptors on the cell surface.
How is hormone receptor–positive breast cancer treated?
Hormone therapy either blocks the body’s ability to produce estrogen or progesterone, or interferes with the effects of hormones on breast cancer cells, which helps to slow or stop the growth of hormone-sensitive tumors.
Ovarian Abation
Ovarian ablation, or treatment that stops or lowers the amount of estrogen made by the ovaries, can be done surgically, through radiation, or using drugs. With surgical treatment (removal of the ovaries) or radiation, the ovarian ablation is typically permanent. Suppressing ovarian function with drugs is temporary, and this group of medicines functions by interfering with signals from the pituitary gland stimulating the ovaries to produce estrogen. Side effects of ovarian suppression may include bone loss, mood swings, depression, and loss of libido.
SERMs
Selective estrogen receptor modulators (SERMs) bind to estrogen receptors, preventing estrogen from binding. In addition to blocking estrogen activity, SERMs can also mimic estrogen effects because of their ability to bind. A SERM called tamoxifen, for example, blocks the effects of estrogen in breast tissue but acts like estrogen in the uterus and bone. Tamoxifen is effective in treating early-stage breast cancer after surgery. Some SERMs can treat advanced or metastatic breast cancer. Side effects of tamoxifen may include risk of blood clots, stroke, cataracts, endometrial and uterine cancers, bone loss in premenopausal women, mood swings, depression, and loss of libido.
Aromatase Inhibitors
Other types of drugs called aromatase inhibitors block the activity of an enzyme called aromatase, which the body uses to make estrogen in the ovaries and in other tissues. These are most effective in postmenopausal women, since premenopausal women produce more aromatase than can be blocked effectively. However, certain aromatase inhibitors can treat early-stage breast cancer in pre and postmenopausal women. Others can treat metastatic cancer (cancer that has spread) in postmenopausal women. Aromatase inhibitors can also be effective in neoadjuvant (pre-surgery) (pre-surgery) treatment of breast cancer in postmenopausal women. Side effects of aromatase inhibitors may include risk of heart attack, angina, heart failure, and hypocholesterolemia, bone loss, joint pain, mood swings, and depression. The aromatase inhibitors used in clinical practice include anastrazole, letrazole and exemestane.
Other antiestrogen drugs, such as fulvestrant, bind to and disrupt the estrogen receptor, preventing estrogen stimulation of the cells. Unlike the SERMS they do not mimic estrogen function in other tissues. These drugs function solely as estrogen antagonists. Side effects of fulvestrant include gastrointestinal symptoms, loss of strength, and pain.
Side effects of hormone therapy vary based on the type of drug or treatment used, and the risks and benefits should be assessed for each patient.
Resistance to hormone therapy
Sometimes, despite the presence of the estrogen receptor or progesterone receptor, cells do not respond to hormone therapy, or they respond initially and become resistant. Laboratory investigation has identified biochemical pathways of resistance. Combinations of drugs to block these resistance pathways, along with hormonal therapy, have been effective against ER positive tumors. Two examples include a drug call everolimus that blocks the MTOR resistance pathways, and a family of drugs called CDK 4-6 inhibitors that block a different resistant pathway. These have shown excellent results in metastatic ER positive breast cancer and are being tested in adjuvant prevention setting in combination with other hormonal therapy. Current examples include palbociclib, ribociclib and abemaciclib.
