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 is used for hormone receptor-positive breast cancers to stop the hormones from binding to the receptors. The main types of hormone therapies are selective estrogen receptor modulators (SERMs), selective estrogen receptor degraders (SERDs), and aromatase inhibitors (AIs).[2]  

The most common side effects of SERMs are hot flashes and vaginal dryness or discharge. If cancer has spread to the bones, a tumor flare causing bone pain is possible. This may lead to a high calcium level in some women. Other rare side effects are possible such as blood clots, stroke, or the development of uterine cancer. Bone thinning may occur in pre-menopausal women, while bones usually strengthened for post-menopausal women taking SERMs. The most common acute (short-term) side effects of SERDs are hot flashes, night sweats, nausea, headache, injection site pain, and bone pain.[2]

AIs tend to have less serious side effects than SERMs. For example, AIs very rarely cause blood clots and never cause uterine cancer. However, there can be additional side effects with AIs such as muscle pain, joint pain, and joint stiffness. For women experiencing joint pain, switching to a different AI may help or a SERM can be tried. AIs also are more likely to lead to bone thinning. If bones become too thin, it can lead to a condition called osteoporosis and increase the risk of bone fractures. For pre-menopausal women, ovarian suppression may be done to stop the production of estrogen by the ovaries, thereby inducing menopause. Ovarian suppression can lead to symptoms of menopause such as hot flashes, night sweats, mood swings, and vaginal dryness.[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.[2] Common side effects of megestrol acetate include diarrhea, nausea, mood swings, weight gain, sweating, rash, insomnia, impotence, high blood pressure, and excess gas. Some serious side effects such as blood clots and the onset or worsening of diabetes are possible.3 Taking high doses of androgens can lead to male-like changes in women such as deepening of the voice, balding, facial hair growth, irregular menstrual cycles, decreased breast size, and increased size of female genitalia. For women with breast cancer taking androgens, additional side effects such as increased thirst, increased urine output, constipation, and confusion are possible.[4] Some side effects of estrogen therapy include nausea, vomiting, headaches, changes in menstrual cycle, rash, muscle cramps, vaginal discharge, and anxiety. In rare cases, estrogen therapy can lead to heart problems, endometrial cancer, or dementia.[5]

Additional targeted therapies such as CDK4/6 inhibitors, PI3K inhibitors, and mTOR inhibitors can make hormone therapy more effective but may cause their own side effects. Side effects of CDK4/6 inhibitors may include fatigue, low blood cell counts (increased risk of infection), nausea, vomiting, diarrhea, mouth sores, headache, and hair loss. In rare cases, CDK4/6 inhibitors may cause lung inflammation. For PI3K inhibitors, potential side effects include fatigue, nausea, vomiting, diarrhea, mouth sores, rash, low blood cell counts, decreased appetite, weight loss, hair loss, low calcium levels, high blood glucose levels, blood clotting problems, and kidney, liver, or pancreatic problems. Severe skin reactions including blistering and peeling are possible. Side effects of mTOR inhibitors can include fatigue, nausea, diarrhea, mouth sores, shortness of breath, cough, low blood cell counts, high blood glucose levels, and high blood lipid (cholesterol and/or triglycerides) counts.[6]

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.     Side Effects of Megace (megestrol) https://www.medicinenet.com/side_effects_of_megestrol/side-effects.htm#megace_megestrol_side_effects_list_for_healthcare_professionals (accessed Jun 11, 2021).

4.     Androgen (Oral Route, Parenteral Route, Subcutaneous Route, Topical Application Route, Transdermal Route) Side Effects https://www.mayoclinic.org/drugs-supplements/androgen-oral-route-parenteral-route-subcutaneous-route-topical-application-route-transdermal-route/side-effects/drg-20069341 (accessed Jun 14, 2021).

5.     Estradiol: Side Effects, Dosages, Treatment, Interactions, Warnings https://www.rxlist.com/consumer_estradiol/drugs-condition.htm (accessed Jun 14, 2021).

6.     Targeted Drug Therapy for Breast Cancer https://www.cancer.org/cancer/breast-cancer/treatment/targeted-therapy-for-breast-cancer.html (accessed Jun 11, 2021).