Systemic Therapy

Hormone (Endocrine) Therapy

Hormone therapy treats hormone receptor (HR) positive breast cancer by blocking the effects of estrogen and progesterone. Around 80% of breast cancers are estrogen receptor (ER) positive and approximately 65% are both ER positive and progesterone receptor (PR) positive.

How Hormone Therapy Works

Hormone therapy works in several ways to block the action of estrogen and progesterone, which can help the growth of HR+ breast cancers:

• Blocks estrogen or progesterone receptors on cancer cells, preventing them from binding with the hormones
• Reduces the number of receptors available for hormone binding
• Suppresses ovarian hormone production in premenopausal women, lowering estrogen levels in the body
• Inhibits aromatase, an enzyme that converts other hormones into estrogen, further reducing estrogen’s effects on cancer cells

When Hormone Therapy is Used

Hormone therapy can be used in early-stage breast cancer (both for neoadjuvant or adjuvant therapy), in metastatic breast cancer, or for prevention in high-risk individuals (e.g., BRCA2 mutation carriers) to reduce the risk of developing breast cancer.

Hormone therapy is generally used for at least 5 years, with treatment sometimes extended based on recurrence risk. The Breast Cancer Index test can help guide decisions on extending therapy.

Types of Hormone Therapy

• Selective Estrogen Receptor Modulators (SERMs): Block estrogen from binding to breast tissue receptors, while stimulating in other tissues (like the bones). Example: tamoxifen, which may also support bone health.
  • Common side effects: Hot flashes, vaginal dryness, increased risk of blood clots, and a small risk of endometrial cancer after menopause
     
• Selective Estrogen Receptor Degraders (SERDs): Blocks estrogen receptor and then destroys the receptor after binding to it. Example: Fulvestrant
  • Common side effects: Reactions at the injection site, fatigue, nausea, hot flashes, and headaches
     
• Aromatase Inhibitors (AIs): Reduce estrogen production, primarily in postmenopausal women. Examples: anastrozole, letrozole, exemestane
  • Common side effects: Joint pain, bone thinning (osteoporosis), hot flashes, fatigue, and increased risk of fractures
     
• Luteinizing Hormone-Releasing Hormone (LHRH) Agonists & Ovarian Suppression: Temporarily stop the ovaries from making estrogen. Examples: goserelin, leuprolide, triptorelin.
  • Common side effects: Menopausal symptoms (hot flashes, night sweats, vaginal dryness), mood changes, low sex drive, and bone loss with long-term use

The right choice of hormone therapy, along with its duration, depends on several factors, including menopausal status, cancer stage, prior treatments, and overall health.

Medical Review by Roochi Arora, MD, FRCPC, August 2025

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