Breast cells have hormone receptors for estrogen and progesterone. When these hormones bind to the receptors, it signals to the cells to grow. Breast cancer cells may have hormone receptors (denoted as “positive”) or not have hormone receptors (denoted as “negative”). When a breast tumor is hormone receptor-positive, the hormones in the body fuel the growth of the cancer.[1] Hormone therapy (also known as endocrine therapy) is used for hormone receptor-positive breast cancers to stop the hormones from binding to the receptors. Hormone therapy is systematic, meaning it can kill cancer cells throughout the whole body, not just in the breast.[2]

Hormone therapy is typically given for at least 5-10 years after surgery to reduce the risk of cancer recurrence. Hormone therapy may also be given before surgery. Additionally, if breast cancer does recur or spreads to other parts of the body, hormone therapy may be used. Hormone therapy can be used to reduce the likelihood of developing breast cancer for women at an increased risk. Hormone therapy typically works by either lowering estrogen levels in the body (AIs), blocking estrogen receptors (SERMs), or damaging estrogen receptors (SERDs).[2]

Toremifene is used less often than tamoxifen and is only used to treat breast cancer that has spread to other parts of the body (metastatic). If tamoxifen has been used and stopped working, toremifene will probably not work. Tamoxifen and Toremifene are both taken orally. Fulvestrant is only approved for use in post-menopausal women and is used to treat advanced breast cancer. SERDs may work if other hormone therapies (SERMs and AIs) have stopped working. Fulvestrant is given as an injection into the buttocks, typically 2 weeks apart for the month and then once a month after. To treat metastatic breast cancer, fulvestrant may be used in combination with a CDK 4/6 inhibitor or PI3K inhibitor[MB1].[2]

SERMs are more commonly used for pre-menopausal women, while AIs are more commonly used for post-menopausal women. In pre-menopausal women, most estrogen is made in the ovaries, but for post-menopausal women the ovaries no longer work but a small amount of estrogen is still produced in the fat tissue. The enzyme that creates the estrogen in the fat tissue is called an aromatase; therefore, AIs block aromatase from making estrogen. For pre-menopausal women, AIs could be used in combination with ovarian suppression. Letrozole, anastrozole, and exemestane are all about equal in preventing cancer recurrence and are taken orally.[2]

By removing or shutting down the ovaries, ovarian suppression effectively induces menopause upon previously pre-menopausal women. This can be done through surgery or with medication. Surgical removal of the ovaries is done in a procedure called an oophorectomy. More often, however, drugs called luteinizing hormone-releasing hormone (LHRH) analogs are used because it is temporary and ovarian function may be restored later.2 In women, LHRH releases the lutenizing hormone which stimulates the ovaries to produce estrogen and progestrone.[3] By giving the body these LHRH analogs, it no longer needs to produces normal LHRH and therefore stops producing estrogen.[4] LHRH analogs can be used alone or combined with another hormone therapy (AIs, tamoxifen, fulvestrant). Some LHRH analogs include goserelin (brand name: Zoladex) and leuprolide (brand name: Lupron). Chemotherapy drugs may also be used for ovarian suppression because they can damage the ovaries so that they stop producing estrogen. With this technique, ovarian function may return later or it may cause permanent menopause.[2]

Tamoxifen and AIs may be used alone or one may be taken after the other. It has been shown that taking an AI either alone or after tamoxifen is more effective and preventing cancer recurrence than tamoxifen alone.[2]

There are other types of hormone therapy that have been used in the past but are rarely used today. These include megestrol acetate (brand name: Megace) which is a synthetic form of progesterone, androgens (male hormones), and high doses of estrogen. These therapies could potentially be used today if other hormone therapies stopped working but tend to have more side effects.[2]

 [MB1]Link to ‘targeted therapy for hormone receptor-positive breast cancer’ article

References

1.     Hormone Receptor Status https://www.breastcancer.org/symptoms/diagnosis/hormone_status (accessed Jun 15, 2021).

2.     Hormone Therapy for Breast Cancer https://www.cancer.org/cancer/breast-cancer/treatment/hormone-therapy-for-breast-cancer.html (accessed Jun 11, 2021).

3.     Luteinizing Hormone https://byjus.com/biology/luteinizing-hormone/#:~:text=In%20the%20female%20reproductive%20system%2C%20the%20Luteinizing%20hormone,ovulation.%20Promotes%20the%20development%20of%20the%20corpus%20luteum. (accessed Jun 11, 2021).

4.     The luteinizing hormone releasing hormone (LHRH) agonists in treatment of metastatic prostate cancer https://prostatecancerinfolink.net/treatment/metastatic/lhrh-agonists-metastatic-prostate-cancer/ (accessed Jun 11, 2021).