Hormone Therapy For Breast Cancer

  • Aleena Khan BSc Biomedical Science Graduate (first-class honours), University of Birmingham, UK
  • Jagadeeswari Vardha MSc in Epidemiology of Infectious Diseases and Antimicrobial resistance, University of Glasgow
  • Saira Loane Master's of Toxicology, Institute of Biomedical Research, University of Birmingham

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Overview 

A breast cancer diagnosis can feel like devastating news. Whether it’s you, a friend or a relative on this journey, it’s not uncommon to feel daunted by the pathways of treatment. However, familiarising yourself with the treatment you may receive is a helpful step forward. Along with the unique type and subtype of cancer determined by testing your cells, hormone receptor (HR) status plays a major part in determining what treatment might work best for you.

HR status indicates whether or not breast cancer cells have specific molecules on their surface, known as receptors. These receptors enable certain hormones (oestrogen and progesterone) to communicate with the cell. Suppose the cancer cells possess a certain level of the oestrogen receptor (ER) or progesterone receptor (PR). In that case, the breast cancer is classed as hormone receptor-positive (HR-positive) or hormone-sensitive.

Oestrogen and progesterone can stimulate the growth of cancer cells. Hormone therapy (also known as endocrine therapy) aims to counter this growth by blocking the effects of these hormones or lowering their levels in the body. 

Sex and gender terminology in this article

This article will use the terms “female” and “male” to describe the sex assigned at birth.

Understanding HR-positive breast cancer

The role of hormones and hormone receptors in HR-positive breast cancer

Hormones act as chemical messengers, travelling through the bloodstream to your organs, muscles, and various other tissues to coordinate numerous essential processes in your body. These processes include growth, sexual function, and mood regulation, extending to perhaps lesser-known roles such as regulating your sleep-wake cycle and blood pressure.1 

Tissues primarily dedicated to hormone production are classified as endocrine glands. The ovaries are endocrine glands responsible for producing oestrogen, progesterone, and testosterone in premenopausal females. Other tissues, such as fat (adipose tissue) also produce oestrogen both before and after menopause, but become the primary source of oestrogen in postmenopausal females.2,3

Under normal conditions, oestrogen and progesterone play key roles in the menstrual cycle, pregnancy, and even bone density before menopause.4, 5 However, these hormones also regulate cell growth; oestrogen and progesterone can bind to their corresponding receptors on the surface of your breast cells, activating these receptors to ultimately trigger cell multiplication.6, 7 Since cancer arises when there is uncontrolled cell growth, hormones can both promote the development of the cancer and accelerate its advance.

Types of HR-positive breast cancer

HR-positive breast cancer can be divided into subtypes according to which specific hormone receptors the breast cells possess. This includes:

  • Oestrogen receptor-positive (ER-positive)
  • Progesterone receptor-positive (PR-positive)
  • Both types of receptor are present: ER/ PR-positive

Hormone therapy is effective for individuals with ER-positive and/ or PR-positive breast cancers. In females, the majority (80%) of HR-positive breast cancers are ER-positive, and most ER-positive cancers also express PR-positive.8 The occurrence of ER-positive breast cancer is even higher in males, at 90%.9 If very low levels of these receptors or none are present, the breast cancer is classed as HR-negative.In such cases, hormone therapy will likely be ineffective, as the treatment lacks its target: the receptors.

Treatment for HR-positive breast cancer: Hormone therapy

Hormone therapy involves blocking the activity of oestrogen and progesterone or lowering their levels in the body to slow or prevent the growth of hormone-sensitive tumours. 

Hormone therapy drugs are placed into several categories according to their shared mode of action, which can then be matched to the individual patient profile. Different drugs may be used to treat each subtype of HR+ breast cancer, including advanced (also known as metastatic or secondary) and recurrent breast cancers. Treatment is generally taken over a prolonged period (5 to 10 years), with its length being tailored to your individual needs, including:

Types of hormone therapy for breast cancer

There are two primary methods by which hormone therapy works: blocking oestrogen production and/ or blocking oestrogen activity.

Blocking oestrogen production

Oestrogen production can either be stopped altogether (ovarian ablation) or suppressed by targeting the main site of production before menopause: the ovaries. This may be achieved in two ways:

  • Temporarily with luteinising-hormone-releasing hormone (LHRH) agonists
  • Permanently by surgically removing the ovaries (oophorectomy) or, less commonly, by targeting them with radiation.10

LHRH is a hormone produced naturally by the body, responsible for regulating oestrogen and progesterone synthesis in the ovaries. Drugs designed to mimic the action of LHRH, called LHRH agonists (also known as gonadotropin-releasing hormone (GnRH) agonists) work by blocking the signals that instruct the ovaries to generate oestrogen and progesterone. These include goserelin (Zoladex) and leuprorelin (Lupron).

Oophorectomies and radiation are less common methods relative to the above means of temporary ovarian suppression and will result in the earlier onset of menopause. However, they may be suggested if you have an increased risk of breast cancer (e.g. due to inheriting certain genes).11

Blocking oestrogen activity

Drugs that work by blocking oestrogen activity fall into two major categories:

  • Blocking oestrogen production: Aromatase inhibitors (AIs)
  • Blocking the effects of oestrogen: Selective oestrogen receptor modulators (SERMs)

AIs and SERMs are the main hormone therapies for those diagnosed with early-stage HR-positive breast cancer after surgery, to help prevent the cancer from recurring (known as adjuvant treatment). Promisingly, research has linked both AIs and SERMs with reducing cancer recurrence (by almost half) and lowering the risk of death, particularly when used as adjuvant treatment.12,13

Aromatase inhibitors 

As suggested by their name, AIs work by blocking an enzyme called aromatase, which is involved in the conversion of oestrogen from other hormones called androgens. Common AIs include:

While both anastrozole and letrozole temporarily inhibit aromatase and exemestane permanently inhibits the enzyme.14

AIs are most effective in postmenopausal females, quickly becoming the most frequently used form of hormone therapy in this group.15 If you are premenopausal, however, AIs are usually given in combination with other drugs that suppress ovarian activity, such as the above-mentioned LHRH agonists. AIS mustn't be used alone in premenopausal females as they carry the risk of increasing levels of oestrogen on account of the ovaries producing more of the hormone in response.16, 17

Selective oestrogen receptor modulators

SERMs block the effects of oestrogen (cell growth) by disrupting the communication between oestrogen and breast cancer cells. The most common SERMs include:

These drugs work by binding to ERs on the surface of cells, thereby blocking oestrogen from interacting with its receptors on breast cancer cells. Tamoxifen is the most commonly prescribed hormonal treatment for breast cancer; it can work on both premenopausal and postmenopausal females, as well as males with breast cancer.18 However, clinical research has shown AIs to be 30% more effective than tamoxifen or raloxifene (another SERM) at preventing breast cancer recurrence in postmenopausal females.16

Toremifene works similarly to tamoxifen but is only used to treat postmenopausal patients with advanced breast cancer.19

As with AIs, SERMs may also be administered alongside LHRH agonists or other means of ovarian suppression in premenopausal individuals. Using LHRH agonists alongside tamoxifen, chemotherapy or both has been shown to reduce the chance of cancer recurrence in premenopausal people with HR-positive breast cancer.20

Other anti-oestrogenic drugs: Selective oestrogen receptor degraders

Drugs fulvestrant (Faslodex) and elacestrant (Orserdu) also bind to ERs. Unlike SERMs, however, they do not mimic the effects of oestrogen and are therefore classed as true anti-oestrogenic drugs and selective oestrogen receptor degraders (SERDs). This distinction arises from their impact on ERs; the binding of a SERD alters the ER's structure, rendering it non-functional and incapable of interacting with oestrogen. 

Fulvestrant is usually given to patients whose cancer no longer responds to AIs or SERMs or postmenopausal patients with advanced breast cancer who have not undergone previous hormone therapy. Elacestrant has more recently been approved in the US.21

When and how you receive hormone therapy

Treatment may be given before surgery to reduce the size of the cancerous lump, or in cases where chemotherapy cannot be tolerated or surgery is delayed (neoadjuvant treatment). More commonly, it is used after surgery to help prevent the cancer from returning (adjuvant treatment). It may also be recommended after chemotherapy, either concurrently with or after post-surgery radiotherapy

The effectiveness of neoadjuvant hormone therapy has been supported by findings of reduced breast tumour size in postmenopausal females, in particular with the use of AIs.22  Research has also shown that taking the SERM tamoxifen as an adjuvant treatment for at least 5 years after surgery has both a lower risk of breast cancer recurrence and death after 15 years.23

Throughout your hormone therapy, you may need to take different drugs or drug combinations. Many hormone therapy schedules now exist beyond tamoxifen alone in the adjuvant setting.24 Some reasons underlying this class switching are:

  • Side effects
  • Cancer progression
  • Changes in menopausal status

These factors, along with your overall health, are taken into account by your doctor when determining the best treatment plan for you.

Side effects of hormone therapies 

Like most cancer treatments, hormone therapy is often accompanied by a number of possible side effects. They can vary depending on the type of treatment, but symptoms can be grouped by the drug’s mode of action. Some  common side effects of hormone therapies include:

  • Experiencing sudden, short-lived bursts of heat, sweating and flushing (hot flushes)
  • Altered menstrual cycles in premenopausal individuals
  • Decreased interest in sexual activity (a loss of libido)
  • Vaginal dryness or discharge
  • Sensations of nausea
  • Joint pain
  • Mood swings
  • Fatigue

You may find these side effects to be worse at the beginning of your treatment, but they usually become less intense after a few weeks or months. Some more serious but less frequent side effects may also arise - these should be communicated to you before receiving your treatment.

Equally, it is important to promptly communicate the onset of any side effects with your doctor who may be able to alleviate, or advise on how to best manage, your symptoms.

Summary

Hormone therapy forms an essential component of care for HR-positive breast cancers. If you or someone is facing HR-positive breast cancer, it may help to remember that the outlook is also generally positive. Treatments, in particular tamoxifen and AIs, provide a high likelihood of living a long, relatively healthy life by reducing the risk of cancer recurrence and death, especially when initiated early. Together with strength, hope, and the expert guidance of healthcare professionals, developing a well-informed understanding of hormonal treatment options can help you and your loved ones feel more confident when navigating your breast cancer journey.

References

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Aleena Khan

BSc Biomedical Science Graduate (first-class honours), University of Birmingham, UK

Aleena is a first-class biomedical science graduate striving to make the world of science more accessible to the everyday person. By combining her love for writing with her teaching experience, she takes a person-centred approach to communicating the explanations behind health and disease. Through her work, Aleena hopes to empower each and every individual with knowledge that is both evidence-based and actionable, ultimately aiming to help them improve their own and others’ wellbeing.

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Klarity is a citizen-centric health data management platform that enables citizens to securely access, control and share their own health data. Klarity Health Library aims to provide clear and evidence-based health and wellness related informative articles. 
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