Hormones like estrogen and progesterone can impact some kinds of breast cancer. Breast cancer cells include receptors (proteins) that bind to estrogen and progesterone, allowing them to proliferate. Hormone or endocrine therapy is a treatment that prevents hormones from binding to these receptors.

Hormone treatment can reach cancer cells nearly anywhere in the body, not just the breast. It's suggested for women who have hormone receptor-positive malignancies. It is ineffective for women whose tumours lack hormone receptors.

When does hormone treatment come into play?

Hormone treatment is frequently used as adjuvant therapy after surgery to help minimize the chance of cancer recurrence.

It is sometimes begun before surgery (as neoadjuvant therapy). It is generally prescribed for a period of 5 to 10 years.

Hormone therapy can also be used to treat cancer that has returned or spread to other regions of the body following treatment.

Also Read: Living Beyond Breast Cancer

What is hormone therapy and how does it work?

Hormone receptor-positive breast cancer accounts for around two out of every three cases. Their cells have estrogen (ER-positive tumours) and/or progesterone (PR-positive cancers) receptors (proteins) that assist the cancer cells in growing and spread.

Hormone treatment for breast cancer comes in a variety of forms. Hormone treatment reduces estrogen levels or prevents estrogen from acting on breast cancer cells in most cases.

Estrogen receptor antagonists are drugs that inhibit estrogen receptors.

These medicines operate by preventing estrogen from driving the growth of breast cancer cells.

Tamoxifen

On breast cancer cells, this medication inhibits estrogen receptors. It prevents estrogen from binding to cancer cells and instructs them to proliferate and develop. Tamoxifen works as an estrogen in other tissues, such as the uterus and bones, while acting as an anti-estrogen in breast cells. As a result, it's known as a selective estrogen receptor modulator (SERM). It can be used to treat both menopausal and non-menopausal women with breast cancer.

Tamoxifen can be used in a variety of ways, including:

• Tamoxifen can be used to help decrease the risk of breast cancer in women who are at high risk.
• Taking tamoxifen for 5 years reduces the risk of ductal carcinoma in situ (DCIS) recurrence in women who have had breast-conserving surgery for hormone receptor-positive DCIS. It also reduces the risk of both breasts developing invasive breast cancer.
• Tamoxifen can assist people with hormone receptor-positive invasive breast cancer who have had surgery to reduce their risks of the disease returning and live longer. It may also reduce the chances of developing new cancer in the opposite breast. Tamoxifen is generally administered for 5 to 10 years, either after surgery (adjuvant therapy) or before surgery (neoadjuvant therapy). This medication is mostly used by women who are still in the early stages of breast cancer and have not yet reached menopause. (Aromatase inhibitors are generally taken instead if you've reached menopause.)

• Tamoxifen can frequently help delay or stop the growth of hormone-positive breast cancer that has spread to other parts of the body, and it may even reduce certain tumours in women with hormone-positive breast cancer that has spread to other parts of the body.
• Another SERM that acts similarly is toremifene (Fareston), although it is used less often and is only licensed to treat metastatic breast cancer in postmenopausal women. If tamoxifen has already been taken and is no longer effective, it is unlikely to function. These are tablets that are taken by mouth.

SERMs have side effects.

• Dryness or discharge in the vaginal area

Some women who have cancer that has spread to their bones may experience a tumour flare along with bone discomfort. This typically goes away fast, but in very rare situations, a woman may acquire an uncontrollable high calcium level in her blood. If this occurs, the therapy may need to be temporarily halted.

Side effects that are less common but more significant are also possible:

• SERMs can raise a woman's risk of uterine cancer after she has gone through menopause. Any unexpected vaginal bleeding should be reported to your doctor straight soon (a common symptom of this cancer). Although most uterine bleeding is not caused by cancer, it should always be treated as soon as possible.
• Another unusual complication is blood clots.
• SERMs can raise a woman's risk of uterine cancer after she has gone through menopause. Any unexpected vaginal bleeding should be reported to your doctor straight soon (a common symptom of this cancer). Although most uterine bleeding is not caused by cancer, it should always be treated as soon as possible
• Another unusual but dangerous adverse effect is blood clots. They generally form in the legs (deep vein thrombosis, or DVT), but a fragment of a clot in the leg might break off and block an artery in the lungs (pulmonary embolism or PE).

Tamoxifen has been linked to strokes in postmenopausal women on rare occasions, so notify your doctor if you're experiencing severe headaches, disorientation, or difficulty speaking or moving.

• Tamoxifen might have varied effects on the bones depending on a woman's menopausal state. Tamoxifen might cause modest bone loss in premenopausal women, while it generally strengthens bones in postmenopausal women. For virtually all women with hormone receptor-positive breast cancer, the advantages of taking these medicines exceed the dangers.

Fulvestrant

Fulvestrant is an estrogen receptor blocker and agonist. This medication isn't a SERM; instead, it works as an anti-estrogen throughout the body. A selective estrogen receptor degrader is what it's called (SERD). Fulvestrant is only authorized for usage in postmenopausal women at this time. It's sometimes used "off-label" in premenopausal women to switch off the ovaries, usually in combination with a luteinizing hormone-releasing hormone (LHRH) agonist (see the section on Ovarian Ablation below).

Fulvestrant is used to treat advanced breast cancer that has not responded to previous hormone treatments.

• When other hormone medicines (such as tamoxifen and typically an aromatase inhibitor) have failed to treat advanced breast cancer, this pill is used alone.
• As an initial hormone therapy or after other hormone therapies have been attempted, in conjunction with a CDK 4/6 inhibitor or a PI3K inhibitor to treat metastatic breast cancer.
• It is administered via injections in the buttocks. The injections are administered every two weeks for the first month. They are then administered once a month after that.

Also Read: Her2 Positive Breast Cancer

Fulvestrant side effects

The following are some of the most common short-term adverse effects:

• Night sweats and/or hot flashes
• Headache
• nausea (mild)
• Injection site discomfort Bone pain

Treatments that reduce the amount of estrogen in the body

Some hormone therapies reduce estrogen levels in the body. Because estrogen promotes the growth of hormone-receptor-positive breast tumours, decreasing estrogen levels can help delay cancer's progression or prevent it from returning.

Most clinicians advocate using an AI at some time during adjuvant therapy for most postmenopausal women with hormone receptor-positive malignancies. At the moment, the usual therapy is to take these medicines for around 5 years, alternating with tamoxifen for at least 5 years, or take in sequence with tamoxifen for at least 3 years. An AI for ten years may be advised for women who are at a higher risk of recurrence. For some women who are unable to take an AI, tamoxifen is an alternative. Tamoxifen used for ten years is thought to be more effective than tamoxifen taken for five years, but you and your doctor will determine the optimal treatment plan for you.

Possible adverse effects of AIs: Compared to tamoxifen, AIs have less significant side effects. They seldom cause blood clots and don't cause uterine cancer. However, they can induce muscular discomfort as well as stiffness and/or pain in joints. The joint discomfort might be akin to having arthritis in several joints at the same time. While switching to a different AI may help with this adverse effect, it has led to some women discontinuing therapy. If this occurs, most doctors advise taking tamoxifen for the remaining 5 to 10 years of hormone therapy.

Because AIs significantly reduce estrogen levels in women after menopause, they can contribute to bone weakening, osteoporosis, and even fractures.

Pre-menopausal women are successfully made post-menopausal by removing or shutting down their ovaries (ovarian suppression), which are the major source of estrogen. Other hormone treatments, such as AIs, may be able to be utilized as a result.

To treat breast cancer, there are various options for removing or shutting down the ovaries:

Oophorectomy is the surgical removal of the ovaries. This is a type of ovarian ablation that is permanent.

Analogues of the luteinizing hormone-releasing hormone (LHRH): The use of these medicines is more common than the use of oophorectomy.

They block the body's signal to the ovaries to produce estrogen, resulting in temporary menopause. Goserelin (Zoladex) and leuprolide are two common LHRH medications (Lupron). They can be used as hormone treatment in premenopausal women alone or combination with other hormone medications (tamoxifen, aromatase inhibitors, fulvestrant).

Medications used in chemotherapy: Some chemotherapy treatments can cause premenopausal women's ovaries to stop producing estrogen. In some women, ovarian function might recover months or years later, while in others, ovarian damage is irreversible and leads to menopause.

Hormone treatment that isn't as well-known

Other hormone therapies that were utilised more often in the past but are now rarely used include:

• Megace (megestrol acetate) is a progesterone-like medication.
• Androgens are male hormones that are produced in the body (male hormones)
• Estrogen in high dosages

These may be viable choices if other kinds of hormone treatment have failed, but they are frequently associated with negative side effects.

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Reference:

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2. Tremont A, Lu J, Cole JT. Endocrine Therapy for Early Breast Cancer: Updated Review. Ochsner J. 2017 Winter;17(4):405-411. PMID: 29230126; PMCID: PMC5718454.