Hormone therapy is a type of systemic therapy that is used to treat hormone receptor (HR) positive (ER/PR+) breast cancers (lobular or ductal). HR+ cancers are fueled by female hormones. These cancers have estrogen and/or progesterone receptors that they use to attach to estrogen/progesterone. This attachment gives cancer cells the signal to grow and divide. Hormone therapy works by inhibiting this attachment. Hormone therapy is a possibility for all stages of breast cancer, including in situ breast cancer (in some cases). Hormone therapy is almost always used as a line of treatment in HR+ metastatic breast cancers (Stage IV). 

 

What is a systemic therapy?  

Systemic therapies are therapies meant to inhibit cancer growth throughout the body, rather than solely in the breast. Systemic therapy is the main treatment for stage IV breast cancers (breast cancers that have spread to organs/bones), and are also used to prevent stage I, II, or III cancers from recurring after surgery and to prevent in situ cancers from becoming invasive

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Hormone Therapy in In Situ vs. Invasive Breast Cancer

-In HR+ in situ (stage 0) breast cancers, hormone therapies such as tamoxifen ( a type of SERM) or an aromatase inhibitor may be given (usually for a five year period), in order to reduce the risk of another in situ or invasive cancer developing later. 

-In HR+ invasive (stages I-IV) breast cancers, hormone therapy is almost always a treatment line in order to prevent or contain cancer metastasis. In stages I-III, hormone therapy is usually coupled with surgery to reduce the risk of cancer recurrence. In stage IV breast cancer, hormone therapy is used to inhibit the growth/spread of cancer that has already metastasized (usually hormone therapy is coupled with chemotherapy or other systemic therapies).

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Types of Hormone Therapies

There are two main types of hormone therapy: Selective Estrogen Receptor Modulators (SERMS) such as tamoxifen and raloxifene, and Aromatase Inhibitors such as exemestane and letrozole. 

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Selective Estrogen Receptor Modulators(SERMS) 

SERMS act at the estrogen receptors on cancer cells, blocking estrogen from attaching to these receptors, and therefore inhibiting cancer growth/division. The most common SERM used to treat breast cancer is tamoxifen. 

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Tamoxifen (Nolvadex/Soltamox)

Tamoxifen is often used in premenopausal or postmenopausal women to treat or prevent breast cancer. 

Who is most likely a candidate for tamoxifen? 

-women with a very high risk of breast cancer (ex: those with mutations/family history, or those who have a history of LCIS) may be eligible to take tamoxifen to prevent breast cancer before it starts

-women who have surgery to treat DCIS or LCIS often take tamoxifen after surgery in order to reduce the risk of another invasive or in situ breast cancer developing in the future (often taken for a five year period) 

-women (usually premenopausal) who have had surgery to treat stages I-III breast cancer often take tamoxifen to lower their cancer recurrence risk; can be used before or after surgery; often taken for 5-10 years depending on recurrence risk

-tamoxifen is often used to treat stage IV metastatic breast cancers, as it helps inhibit the growth/spread of cancer that has already metastasized.

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Possible Side Effects of Tamoxifen 

 

Common Side Effects:

-the most common side effects associated with tamoxifen are menopausal symptoms, such as hot flashes, irregular or ceased menstrual cycles, and vaginal dryness

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Rare Side Effects: 

These side effects are much more serious, but very rare.

-may increase risk of blood clots in the lungs or legs; this risk is less than 1%, but those who have a history of blood clots/are at high risk may not be eligible for tamoxifen

-may increase risk of endometrial cancer (<1%)

-may increase risk of cataracts (clouding of the eye's natural lens)

-in pre-menopausal women, tamoxifen may cause weakeaned bones (not an issue in postmenopausal women)

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Aromatase Inhibitors 

Aromatase Inhibitors, like SERMS, are used to treat HR+ breast cancer. AI's work by inhibiting aromatase, an enzyme that converts natural steroids in your body into estrogen. By preventing the production of estrogen, the ER and PR + cancers no longer have estrogen to bind to, and therefore cannot grow and divide. AI's are only for post menopausal ​women, because before menopause, your ovaries make estrogen. 

However, premenopausal women can also take AI's, if their ovaries are suppressed via: 

          -Luteinizing hormone releasing hormone agonists: drugs (usually administered through a shot) that put women into temporary menopause by temporarily stopping the ovaries from producing estrogen. This is the most common way to suppress the ovaries. 

          -oophorectomies (surgery to remove the ovaries) allow premenopausal women to take AI's.

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​The most common aromatase inhibitors are letrozole (femara), exemestane (aromasin), and anastrozole (arimidex). 

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Similar to SERMS, AI's can be used for breast cancer treatment or prevention (in postmenopausal or ovarian suppressed women).

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For postmenopausal women, AI's are often used after five years of tamoxifen (but can also be used by themselves), and lower the recurrence risk, risk of bilateral breast cancer, and risk of death. 

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Side Effects of Aromatase Inhibitors 

Unlike tamoxifen, AI's don't increase the risk of blood clots or endometrial cancers; however, they do have other risks: 

-bone weakness/thinning due to very low estrogen levels, putting you at higher risk of fractures

-muscle pain and/or joint stiffness/pain (exercise is a very effective way to alleviate these symptoms)

-hot flashes 

-vaginal dryness

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