All About Breast Cancer Hormone Receptor Status

Learn what breast cancer hormone receptors are and why they’re important in diagnosis and treatment

Thanks to research, there are many FDA-approved treatments for breast cancer. But how do doctors determine the best therapies for each patient? Part of that process relies on identifying your breast cancer hormone receptor status.

What are breast cancer hormone receptors, and why is their presence—or lack thereof—so important in developing a treatment plan that’s most likely to produce the best outcomes? Read on for the answers to these questions and more.

What are hormone receptors in breast cancer?

Hormone receptors are proteins located in cells that are activated when hormones bind to them. Healthy breast cells and some breast cancer cells have receptors for estrogen and/or progesterone—hormones that, among other functions, work together to support your reproductive health.

As estrogen and progesterone circulate through your body, they attach to corresponding receptors in breast cells, guiding normal cell development and function. But when these hormones bind to breast cancer cells that have receptors, they can alter breast cancer’s growth. Estrogen, for example, promotes growth.

What is hormone receptor–positive breast cancer​?

Hormone receptor–positive (HR+) breast cancer is a subtype of the disease in which the cancer cells have estrogen and progesterone receptors. An estimated four out of five breast cancers are hormone receptor–positive, with older women more likely to be diagnosed than younger women.

There are three subsets of hormone receptor-positive breast cancer:

• Estrogen receptor–positive breast cancer (ER+)
• Progesterone receptor–positive breast cancer (PR+)
• Estrogen receptor– and progesterone receptor–positive breast cancer (ER/PR+)

Estrogen receptor–positive breast cancer is the most common, making up about 80 percent of all breast cancers. Also frequently seen is estrogen receptor– and progesterone receptor–positive breast cancer: More than 50 percent of estrogen receptor–positive breast cancers are also positive for progesterone receptors. Progesterone receptor–positive/estrogen receptor-negative breast cancer is the least common subtype.

While estrogen and progesterone are considered female hormones, male breast cancer can also be hormone receptor–positive. Men do produce estrogen and progesterone, just in much smaller amounts. About nine out of 10 breast cancers in men are positive for hormone receptors.

How are tumors tested for hormone receptor status?

Typically, doctors determine whether your cancer is positive for hormone receptors with an immunohistochemistry test (IHC). Your doctor removes a sample of malignant breast tissue via a biopsy or surgery, which is then sent to a lab to measure levels of hormone receptors. The results of this test are included in your pathology report.

If your cancer is hormone receptor–positive, it means that at least one percent of the cells in your sample have estrogen and/or progesterone receptors. You’ll also see an Allred score, which is a measure of how many hormone receptor–positive cells were found as well as their intensity, meaning how well they appeared during the test.

Why is hormone receptor testing important?

If testing shows that you have hormone receptor–positive breast cancer, your doctor can treat it with hormone therapy. Also called endocrine therapy, hormone therapy slows or stops the growth of breast cancer by preventing your body from producing hormones or by interfering with the effects hormones have on breast cancer cells. The main categories of hormone therapy are those that:

• Suppress or block ovarian function: Medications called gonadotropin-releasing hormone (GnRH) agonists—also known as luteinizing hormone–releasing hormone agonists—work by interfering with signals that tell the ovaries to produce estrogen. Examples of ovarian function-blockers include goserelin (Zoladex®) and leuprolide (Lupron®). Alternatively, ovarian function can be blocked permanently by surgically removing the ovaries (a procedure called oophorectomy).
• Lower or stop estrogen production: Aromatase inhibitor drugs block the activity of aromatase, an enzyme your body uses to make estrogen in the ovaries and other tissues. Some aromatase inhibitors do this temporarily, such as anastrozole (Arimidex®) and letrozole (Femara®), while others like exemestane (Aromasin®) inactivate aromatase permanently.
• Block estrogen’s ability to trigger the growth of breast cancer cells: Your doctor may prescribe a selective estrogen receptor modulator (SERM) such as tamoxifen (Nolvadex®) or toremifene (Fareston®), which prevents estrogen that’s circulating in your body from binding to the receptors. Selective estrogen receptor degraders (SERDS), such as fulvestrant (Faslodex®), work in a slightly different way. When the SERD binds the receptor, it is targeted for degradation or destruction.

Depending on the stage of your cancer, hormone therapy may be used in addition to other treatments such as chemotherapy, radiation therapy, and surgery. It is also sometimes combined with other newer therapies that target unique characteristics of cancer cells and can make hormone therapy more effective. Examples include abemaciclib (Verzenio®), alpelisib (Piqray®), palbociclib (Ibrance®), ribociclib (Kisqali®), and everolimus (Afinitor®).

What is hormone receptor–negative breast cancer​?

Hormone receptor–negative breast cancer (HR–) lacks receptors for estrogen and/or progesterone. This subtype is most likely to occur in premenopausal women. Unfortunately, it is more aggressive than hormone receptor–positive breast cancers, and it is also harder to treat since hormone therapy is ineffective.

Triple–negative breast cancer (TNBC) is an example of hormone receptor-negative breast cancer. In addition to lacking estrogen or progesterone receptors, TNBC is also negative for a protein called human epidermal growth factor receptor 2 (HER2) that helps breast cancer cells grow rapidly. Unfortunately, the lack of HER2 in TNBC makes it far less likely to respond to drugs that target the HER2 protein, such as monoclonal antibodies and kinase inhibitors. While there are fewer treatment options for TNBC, new drugs are emerging.

HER2-positive breast cancers may be hormone receptor–positive—this is called triple-positive breast cancer. In addition to hormone therapies, HER2-targeting drugs are a treatment option for this form.

BCRF research on HR-positive breast cancer

Since its founding, BCRF investigators have played a pivotal role in developing and testing many hormone-based breast cancer treatments, including aromatase inhibitors, SERMs, and ovarian suppression. In addition to expanding treatment options for the most-diagnosed subtype of breast cancer, these advances have reduced recurrence and mortality and prevented cancer from developing in high-risk individuals.

More recently, BCRF researchers have been studying why some breast cancers become resistant to these treatments, which can lead to metastasis. They are exploring how hormones affect breast cancer risk, including the role of estrogen from body fat. BCRF is also supporting research on alternatives to hormone therapy to help improve postmenopausal thrivers’ health and quality of life.

These advances would not have been possible without the fundamental understanding of hormone receptor status in breast cancer. Findings by BCRF investigators and other researchers have paved the way for lifesaving treatments, helping doctors tailor therapies, overcome resistance, and find new ways to prevent and manage this complex disease.