Endocrine (Hormone) 

Overview

Hormones are naturally produced in the body. They regulate proper cell development and activity. Prior to menopause, the ovaries generate the hormones oestrogen and progesterone, according to a vocabulary entry. Oestrogen is produced in body fat and muscle after menopause. Some breast cancer cells can be stimulated by these hormones.

Hormones can encourage the growth of certain breast cancer cells. Hormone treatment reduces the quantity of hormones in the body or prevents them from reaching breast cancer cells. There are several varieties, and the one you require is determined by a variety of criteria. They may have unintended consequences.

 

What are hormones and hormone receptors?

Hormones are chemicals that act as chemical messengers in the body. They influence the activity of cells and tissues throughout the body, frequently reaching their targets via the circulation.

Premenopausal women's ovaries generate estrogen and progesterone, as do several other tissues, including fat and skin, in both premenopausal and postmenopausal women and men. Estrogen aids in the development and maintenance of female sex traits, as well as the growth of long bones. Progesterone affects the menstrual cycle and pregnancy.

Some breast cancers, known as hormone-sensitive (or hormone-dependent) breast cancers, are also aided in their development by estrogen and progesterone. Hormone-sensitive breast cancer cells possess proteins called hormone receptors (ERs and PRs) that get activated when hormones attach to them. When receptors are triggered, they alter the expression of particular genes, which can encourage cell growth.

Doctors examine samples of tumor tissue retrieved during surgery to identify whether breast cancer cells possess hormone receptors. If the tumor cells possess estrogen receptors, the malignancy is known as estrogen receptor positive (ER positive), estrogen sensitive (ES), or estrogen responsive (ER responsive). 

Similarly, if progesterone receptors are found in the tumor cells, the malignancy is referred to be progesterone receptor positive (PR or PgR positive). Breast cancers with estrogen and/or progesterone receptors are commonly referred to as hormone receptor positive (HR positive). The vast majority of ER-positive breast tumors are also PR positive.

Breast cancers that lack ERs are referred to as ER negative, while those that lack both ER and PR may be referred to as HR negative. Approximately 67%-80% of female breast cancers are ER positive. Approximately 90% of male breast cancers are ER positive, and 80% are PR positive.

 

What is Endocrine (Hormone) therapy?

Hormone therapy (also known as hormonal therapy, hormone treatment, or endocrine therapy) slows or prevents the growth of hormone-sensitive cancers by interfering with the effects of hormones on breast cancer cells or by limiting the body's ability to manufacture hormones. Hormone-insensitive tumors lack hormone receptors and do not react to hormone treatment.

Menopausal hormone therapy (MHT)—treatment with estrogen alone or in combination with progesterone to assist alleviate menopausal symptoms—should not be confused with hormone therapy for breast cancer. The effects of these two forms of therapy are diametrically opposed: hormone therapy for breast cancer inhibits the growth of HR-positive breast cancer, but MHT can increase the growth of HR-positive breast cancer. As a result, when a woman receiving MHT is diagnosed with HR-positive breast cancer, she is typically advised to discontinue the medication. 

 

When Hormone Therapy is Given?

Hormonal treatment medications are utilized in four different ways: To reduce the size of the cancer before surgery: If your breast cancer is big and hormone receptor-positive, your doctor may advise you to try hormonal treatment before surgery to decrease the malignancy. Because therapies administered before to surgery are referred to as neoadjuvant treatments, hormonal therapy administered in this manner is referred to as neoadjuvant hormonal therapy. To minimize the likelihood of recurrence: If you have early-stage hormone receptor-positive breast cancer, your treatment plan will likely involve hormonal therapy following surgery as well as other therapies to lower the chance of the disease returning (recurrence).

Adjuvant therapies are those administered after surgery, therefore hormonal therapy administered in this manner is known as adjuvant hormonal therapy. To slow the progression of advanced-stage cancer: If you've been diagnosed with advanced-stage, hormone receptor-positive breast cancer, hormonal treatment can be used to assist slow the progression of the disease. 

To lessen the possibility of an initial diagnosis: Hormonal treatment can also be used to minimize the risk of breast cancer in women who have not yet been diagnosed. Women who have a substantially greater than usual risk of developing hormone receptor-positive breast cancer may take a hormonal therapy drug as a prophylactic measure.

 

What types of hormone therapy are used for breast cancer?

 

Several strategies are used to treat hormone-sensitive breast cancer:

Blocking ovarian function:

Because the ovaries are the primary source of estrogen in premenopausal women, ovarian activity can be eliminated or suppressed to lower estrogen levels in these people. Ovarian ablation is the process of preventing ovarian function. Ovarian ablation can be performed surgically during an oophorectomy (removal of the ovaries) or by radiation therapy. Ovarian ablation of this sort is typically permanent.

Alternatively, gonadotropin-releasing hormone (GnRH) agonists, also known as luteinizing hormone-releasing hormone (LHRH) agonists, can be used to temporarily decrease ovarian activity. These medications interfere with signals that drive the ovaries to make estrogen by imitating GnRH. Ovarian suppression medicines include goserelin (Zoladex) and leuprolide (Lupron).

 

Blocking estrogen production: 

Aromatase inhibitors are medications that suppress the function of an enzyme called aromatase, which the body utilizes to produce estrogen in the ovaries and other tissues. Aromatase inhibitors are mostly utilized in postmenopausal women since premenopausal women's ovaries generate too much aromatase for the inhibitors to properly block. These medications, however, can be utilized in premenopausal women if combined with an ovarian function suppressant.

Aromatase inhibitors authorized by the FDA include anastrozole (Arimidex) and letrozole (Femara), both of which temporarily suppress aromatase, and exemestane (Aromasin), which inhibits aromatase permanently.

 

Blocking estrogen’s effects: 

Several medications work against estrogen's potential to increase the development of breast cancer cells:

• Selective Estrogen Receptor Modulators (SERMs) bind to estrogen receptors and inhibit estrogen from binding. Tamoxifen (Nolvadex) and toremifene are two SERMs authorized by the FDA for the treatment of breast cancer (Fareston). SERMs can possibly not only inhibit estrogen action (by blocking estrogen from attaching to its receptor) but also mimic the effects of estrogen, depending on where they are produced in the body. Tamoxifen, for example, limits the effects of estrogen in breast tissue while acting like estrogen in the uterus and bone.
• Other antiestrogen medications, such as fulvestrant (Faslodex), function in a slightly different way to prevent the effects of estrogen. Fulvestrant, like SERMs, binds to the estrogen receptor and acts as an estrogen blocker. Fulvestrant, unlike SERMs, does not imitate estrogen. Be a result, it is referred to as a pure antiestrogen. Furthermore, when fulvestrant interacts to the estrogen receptor, the receptor is destroyed.

 

How is hormone therapy used to treat breast cancer?

There are three main ways that hormone therapy is used to treat hormone-sensitive breast cancer:

Adjuvant therapy for early-stage breast cancer:

Tamoxifen is FDA-authorized for adjuvant hormone therapy of ER-positive early-stage breast cancer in premenopausal and postmenopausal women (and males), and the aromatase inhibitors anastrozole, letrozole, and exemestane are approved for similar purpose in postmenopausal women.

According to research, women who get at least 5 years of adjuvant tamoxifen medication following surgery for early-stage ER-positive breast cancer had a lower chance of recurrence, including a new breast cancer in the other breast, and a lower risk of mortality after 15 years.

Until recently, the majority of women who got adjuvant hormone treatment to minimize the risk of recurrence of breast cancer took tamoxifen every day for 5 years. However, with the emergence of novel hormone medications (such as aromatase inhibitors), some of which have been clinically compared to tamoxifen, various approaches to hormone therapy have become prevalent.

For example, instead of tamoxifen, some women may take an aromatase inhibitor every day for 5 years. After 5 years of tamoxifen, other women may receive further therapy with an aromatase inhibitor. Finally, after 2 or 3 years of tamoxifen, some women may move to an aromatase inhibitor, for a total of 5 or more years of hormone treatment. Adjuvant treatment with an aromatase inhibitor lowers the incidence of recurrence and increases overall survival in postmenopausal women treated for early-stage breast cancer when compared to adjuvant tamoxifen.

Some premenopausal women with early-stage ER-positive breast cancer may be treated with ovarian suppression with an aromatase inhibitor, which has been shown to have a greater rate of recurrence-free survival than ovarian suppression plus tamoxifen or tamoxifen alone.

Tamoxifen is often given first to men with early-stage ER-positive breast cancer who are receiving adjuvant treatment. Those on an aromatase inhibitor are frequently also taking a GnRH agonist. Adjuvant hormone treatment decisions are challenging and must be determined on an individual basis in cooperation with an oncologist.

 

Treatment of advanced or Metastatic breast cancer: 

Several hormone therapies are licensed for the treatment of metastatic or recurring hormone-sensitive breast cancer. Hormone therapy is also a therapeutic option for ER-positive breast cancer that has returned after treatment in the breast, chest wall, or adjacent lymph nodes.

Tamoxifen and toremifene, two SERMs, are licensed to treat metastatic breast cancer. Fulvestrant, an antiestrogen, has been authorized for postmenopausal women with metastatic ER-positive breast cancer that has spread following therapy with other antiestrogens. Fulvestrant is also authorized for postmenopausal women who have not previously had hormone treatment and have HR-positive, HER2-negative locally advanced or metastatic breast cancer. It may also be used in premenopausal women who have had ovarian ablation.

The aromatase inhibitors anastrozole and letrozole are licensed for use as first-line treatment in postmenopausal women with metastatic or locally progressed hormone-sensitive breast cancer. Both of these medications, as well as the aromatase inhibitor exemestane, are licensed to treat postmenopausal women with advanced breast cancer whose illness has deteriorated following tamoxifen therapy. Men with advanced breast cancer who take an aromatase inhibitor are also given a GnRH agonist.

Some women with advanced breast cancer are treated with a combination of hormone therapy and one of several targeted therapies: 

• Palbociclib (Ibrance) is authorized as a first therapy in postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer in conjunction with letrozole. Palbociclib reduces the development of HR-positive breast cancer cells by inhibiting two cyclin-dependent kinases (CDK4 and CDK6). Palbociclib is also licensed for use in conjunction with fulvestrant to treat postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer that has progressed despite treatment with another hormone therapy.
• Abemaciclib (Verzenio), another CDK4 and CDK6 inhibitor, is licensed for use in conjunction with fulvestrant in postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer that has progressed despite hormone therapy. Abemaciclib is also licensed for use alone in women and men with HR-positive, HER2-negative advanced or metastatic breast cancer whose condition worsened following treatment with hormone therapy and prior chemotherapy for metastatic disease.
  
  
• Ribociclib (Kisqali), another CDK4/6 inhibitor, is licensed for use in postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer that has not been treated with hormone therapy in conjunction with an aromatase inhibitor.
• Tykerb (lapatinib) is licensed for use in conjunction with letrozole to treat HR-positive, HER2-positive metastatic breast cancer in postmenopausal women who require hormone treatment. It is a small-molecule inhibitor of the tyrosine kinases HER2 and EGFR.
• Alpelisib (Piqray) is authorized to treat HR-positive, HER2-negative breast cancer with a PIK3CA gene mutation. It is used in conjunction with fulvestrant to treat postmenopausal women and men with advanced or metastatic breast cancer that has worsened during or after hormone therapy treatment.
• Hormone treatment plus trastuzumab with or without pertuzumab may be given to certain patients with advanced breast cancer who are HER2 and HR positive.

Neoadjuvant treatment of breast cancer: Clinical studies have been conducted to investigate the use of hormone treatment to treat breast cancer in order to minimize tumor growth prior to surgery (neoadjuvant therapy). These studies have demonstrated that neoadjuvant hormone treatment, particularly with aromatase inhibitors, can reduce the growth of breast cancers in postmenopausal women, but it is unclear how effective it is in premenopausal women.

Hormone therapy is occasionally used as a neoadjuvant treatment for HR-positive breast cancer in postmenopausal women who cannot take chemotherapy or who need to postpone surgery.

 

Can Endocrine therapy be used to prevent breast cancer?

Yes. Most breast cancers are ER positive, and clinical trials have been conducted to see whether hormone treatment may be used to prevent breast cancer in women who are predisposed to the illness.

The FDA has authorized tamoxifen and raloxifene to lower the chance of developing breast cancer in women at high risk of the illness. Tamoxifen can be used for this purpose independently of menopause. Raloxifene is exclusively approved for postmenopausal women.

 

What are the side effects of hormone therapy?

The adverse effects of hormone therapy are mostly determined by the exact medicine or treatment. The advantages and risks of hormone treatment should be carefully considered for each individual. A popular adjuvant therapy switching strategy in which patients receive tamoxifen for 2 or 3 years, followed by an aromatase inhibitor for 2 or 3 years, may give the optimal mix of advantages and dangers of these two forms of hormone therapy.

All hormone therapy cause hot flashes, nocturnal sweats, and vaginal dryness as adverse effects. Hormone treatment may also cause menstrual irregularities in premenopausal women. The following are some of the less common yet dangerous adverse effects of hormone treatment medicines.

Tamoxifen

• Risk of blood clots, especially in the lungs and legs
• Stroke
• Cataracts
• Endometrial cancer and uterine sarcoma
• Bone loss in premenopausal women, but no increased risk of fracture
• Mood swings, depression, and loss of libido
• In men: headaches, nausea, vomiting, skin rash, impotence, and loss of libido

Raloxifene

• Risk of blood clots, especially in the lungs and legs
• Stroke in certain subgroups

Ovarian suppression

• Bone loss
• Mood swings, depression, and loss of libido

Aromatase inhibitors

• Risk of heart attack, angina, heart failure, and hypercholesterolemia
• Bone loss
• Joint pain
• Mood swings and depression

Fulvestrant

• Gastrointestinal symptoms, including nausea, vomiting, and constipation
• Weakness and fatigue
• Pain, including bone pain, back pain, musculoskeletal pain, joint pain, and in the extremities 
• Headache
• Hot flashes
• Breathing problems, including painful breathing, shortness of breath, and cough
• Loss of appetite

 

Conclusion 

Hormonal treatment, also known as anti-estrogen therapy, endocrine therapy, or hormone therapy, is used to treat hormone receptor-positive breast cancer at all stages.