Hormones are chemical messengers that regulate specific body functions, such as reproduction. They are produced by various glands in the body and enter the bloodstream where they travel to other tissues and exert their influence. Hormonal therapy is used in cancer treatment to augment or interfere with the activity of certain hormones that can influence the growth of tumors.
Who Can Benefit From Hormonal Therapy
Hormonal therapy is designed to take advantage of the fact that many breast cancers are hormone sensitive. Breast cancer that is hormone sensitive may be estrogen receptor positive or progesterone receptor positive, depending on which hormone they react to. The hormones, estrogen or progesterone, are able to bind to cancer cells and stimulate growth and division. Hormonal therapy prevents the binding of these hormones to the cancer cells. This stops the cells from growing and, in doing so, prevents or delays breast cancer recurrence. It can also lower the risk of a second, independent breast cancer.
Tissue testing can determine if a cancer is sensitive to hormones. Cancers that are not hormone receptor positive do not appear to benefit from hormonal therapy, either to prevent recurrence, or to prevent second cancers.
While the vast majority of women who have hormone-sensitive breast cancer will benefit from hormonal therapy, there may be times when the risks may outweigh the potential benefits. Your doctor will help you weigh the risks and benefits.
Methods of Hormonal Therapy
The goal of hormonal therapy is to prevent hormones from attaching to cancer cells and helping cancer grow. This may be done in a number of ways:
- Medicines are used to block the function of hormones
- Destruction of ovarian tissue to suppress hormone production in the ovaries—ablation can be done with medicines, radiation, or surgery
- Medicines are used to suppress hormone production outside of the ovaries by other tissues
Hormonal therapy may include:
- Selective estrogen receptor modulators (SERMs)
- Aromatase inhibitors
- Estrogen receptor down-regulators
- Luteinizing hormone-releasing hormone (LHRH) agonists
- Other hormonal agents, including androgens
- Ovarian ablation
A commonly used SERM is raloxifene. This medicine is used to treat osteoporosis. In postmenopausal women with osteoporosis who have been treated with raloxifene, this medicine has been shown to reduce the risk of breast cancer.
Raloxifene is not yet approved for use in breast cancer treatment. Its benefits, compared to tamoxifen, are being evaluated in the STAR prevention trial. Some reports have found a lower risk of uterine cancer among women taking raloxifene as compared with women taking tamoxifen. The development of uterine cancer is known to be influenced by estrogen-like activity. Raloxifene has been associated with an increased risk of blood clots.
Aromatase inhibitors may be more effective than tamoxifen in both early and advanced stages of breast cancer. Aromatase inhibitors work by inhibiting the conversion of androgens into estrogens. Androgens are commonly referred to as male hormones, but they are found in both men and women. A small amount of androgen is continuously converted into estrogen by the enzyme aromatase. Aromatase inhibitors block the action of aromatase, leaving less estrogen available to stimulate estrogen receptors on cancer cells.
Aromatase inhibitors are used primarily in postmenopausal women. These drugs are generally taken by mouth in tablet form on a daily basis.
Drugs in this class include:
- Letrozole
- Anastrozole
- Exemestane
When compared to tamoxifen, anastrazole was equally as or more effective than tamoxifen for:
- Preventing breast cancer recurrence
- Preventing second breast cancers
- Treatment of early- and late-stage breast cancer
The primary side effect of aromatase inhibitors is an increased risk of osteoporosis (including bone thinning and hip fractures). Therefore, women who use aromatase inhibitors need to have their bone densities measured on a regular basis, and may need medicines to improve bone density such as bisphosphonates, calcium, and vitamin D. Exercise also helps with bone density.
Estrogen receptor down-regulators bind to estrogen receptors on cancer cells and block the receptors so that estrogen cannot enter the cancer cell. This is a complicated process, as certain drugs can act as blockers in one tissue or situation and act like estrogen in other tissues or situations. Two drugs in this class are tamoxifen and fulvestrant.
Tamoxifen is used for both treatment and prevention of breast cancer. It attaches to the estrogen receptor which prevents the estrogen from binding to the cancer cell. Tamoxifen is a standard treatment for women with hormone receptor-positive breast cancer.
Possible side effects and complications associated with tamoxifen include the following:
- Blood clots
- Endometrial changes, such as hyperplasia
- Endometrial polyps
- Uterine cancer
Fulvestrant, like tamoxifen, attaches to the estrogen receptor. However, unlike tamoxifen, it destroys the receptor, thereby blocking all estrogen activity. It is given once per month by intramuscular injection for as long as it is beneficial in the treatment of advanced or metastatic breast cancer.
Luteinizing hormone (LH) is secreted from cells in the pituitary gland and stimulates the ovaries to produce and secrete estrogen. LHRH agonists are used to block the action of LH. Doing so blocks ovarian production of estrogen. LHRH agonists are used for chemical ovarian ablation.
Androgens, progesterone, and progestational agents have been used to treat advanced, hormone-sensitive breast cancer when other medicines have not been effective.
Ovarian ablation is the destruction or removal of ovarian tissue. The reduction of tissue decreases the amount of hormones being produced in the body. It is useful for pre- and perimenopausal women only.
The most common method used is called chemical ovarian ablation. Goserelin is a medicine that reduces production of LH from the pituitary gland, which leads to a reduction of estrogen. This can result in shrinking the tumor or slowing the progression of cancer.
Goserelin is injected under the skin of the upper abdomen every 28 days. This treatment is used primarily in premenopausal women with early-stage receptor-positive breast cancer.
Goserelin can be used alone or with other forms of treatment. Further study is needed to determine if ovarian ablation is more effective when combined with other treatments or when given alone.
Ovarian ablation may also be done with surgery or radiation. Chemical ovarian ablation is the preferred method because, unlike the other options, it is temporary, and fertility may be restored after treatment. Fertility restoration depends on many factors, including whether or not other treatments have caused permanent damage.
Side Effects
The following side effects may occur with hormonal treatments:
- Hot flashes
- Decreased sexual desire
- Weight gain
- Swelling and tenderness of the breasts
- Headaches
- Bone pain
A variety of treatments are available to help manage side effects including medicine, lifestyle changes, and alternative treatments. In some cases, hormonal therapy treatment may be adjusted to reduce severe side effects. The earlier the side effects are addressed, the more likely they will be controlled with a minimum of discomfort.
References
Breast cancer in women. EBSCO DynaMed website. Available at: https://www.dynamed.com/condition/breast-cancer-in-women . Accessed October 3, 2020.
Endocrine therapy for early and locally advanced breast cancer. EBSCO DynaMed website. Available at: https://www.dynamed.com/management/endocrine-therapy-for-early-and-locally-advanced-breast-cancer . Accessed October 3, 2020.
Endocrine therapy for metastatic breast cancer. EBSCO DynaMed website. Available at: https://www.dynamed.com/management/endocrine-therapy-for-metastatic-breast-cancer . Accessed October 3, 2020.
Goserelin. National Cancer Institute website. Available at: https://www.cancer.gov/about-cancer/treatment/drugs/goserelinacetate. Accessed October 3, 2020.
Hormone therapy for breast cancer. American Cancer Society website. Available at: https://www.cancer.org/cancer/breast-cancer/treatment/hormone-therapy-for-breast-cancer.html. Accessed October 3, 2020.
Treatment of hot flashes in patients with breast cancer. EBSCO DynaMed website. Available at: https://www.dynamed.com/management/treatment-of-hot-flashes-in-patients-with-breast-cancer . Accessed October 3, 2020.
Treatment option overview. National Cancer Institute website. Available at: https://www.cancer.gov/types/breast/patient/breast-treatment-pdq#section/%5F185. Accessed October 3, 2020.