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Side Effects Of Hormone Suppression Therapy

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Tamoxifen And Breast Cancer Prevention

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A large study by the National Cancer Institute looked at whether tamoxifen lowered cases of breast cancer in healthy women who were known to be likely to get the disease. The results of the trial showed a 50% reduction in breast cancer in the women who took the drug.

Studies have also shown that tamoxifen lessens the risk of breast cancer returning in women who have had the earliest form of the disease, ductal carcinoma in situ .

For The Population Studied As A Whole There Was An Overall Deterioration In The Quality Of Life At Two Years From Diagnosis This Deterioration Was Greater In Patients Who Had Received Hormone Therapy Especially After The Menopause By Contrast Chemotherapy Had A Bigger Effect On Quality Of Life In Non

It is important in the future that we are able to predict which women are going to develop severe symptoms with anti-hormonal treatment so that we can support them, added Dr Vaz-Luis. While it has been shown that hormone therapy provides a real benefit in reducing the relapse rate of hormone-dependent cancers which represent 75% of all breast cancers, the deterioration in quality of life may also have a negative effect on patient adherence to treatment. It is, therefore, important to offer them symptomatic treatment, in particular for menopausal symptoms, musculoskeletal pain, depression, severe fatigue and cognitive dysfunction and to combine this with supportive measures such as physical exercise and cognitive behaviour therapy.

Learn More About How Hormone Therapy Is Used To Target Cancer Cells

Hormone therapy may also be called endocrine therapy or hormone-blocking therapy.

Some cancers grow in response to particular hormones. These cancers are known as hormone-dependent cancers. They include some types of breast, uterine and prostate cancers. The aim of hormone therapy is the slow or stop the growth of hormone receptor positive cells.

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When Is Hormone Therapy Used

Hormone therapy may be used:

  • If the cancer has spread too far to be cured by surgery or radiation, or if you cant have these treatments for some other reason
  • If the cancer remains or comes back after treatment with surgery or radiation therapy
  • Along with radiation therapy as the initial treatment, if you are at higher risk of the cancer coming back after treatment
  • Before radiation to try to shrink the cancer to make treatment more effective

What Are Male Sex Hormones

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Hormones are substances that are made by glands in the body. Hormones circulate in the bloodstream and control the actions of certain cells or organs.

Androgens are a class of hormones that control the development and maintenance of male characteristics. The most abundant androgens in men are testosterone and dihydrotestosterone .

Androgens are required for normal growth and function of the prostate, a gland in the male reproductive system that helps make . Androgens are also necessary for prostate cancers to grow. Androgens promote the growth of both normal and cancerous prostate cells by binding to and activating the androgen receptor, a protein that is expressed in prostate cells . Once activated, the androgen receptor stimulates the expression of specific genes that cause prostate cells to grow .

Almost all testosterone is produced in the testicles a small amount is produced by the adrenal glands. Although prostate cells do not normally make testosterone, some prostate cancer cells acquire the ability to do so .

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Why Does Hormone Therapy Cause Side Effects

Hormones are chemicals made by the body that move through your bloodstream. They control the activity of certain cells or organs. Changes to the amount of a hormone in your body can interfere with a specific activity in the body and cause side effects. Some hormones affect several body functions, so hormone therapy can cause many different side effects.

Side Effects Of Hormone Therapy In Men

Many men find that the side effects are often worse at the start of treatment. They usually settle down after a few weeks or months.

The side effects you might have depend on the type of hormone therapy that you are having.

Some side effects are common to all hormone therapies. Some vary from drug to drug. You might not have all of these side effects.

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Guidelines On Ovarian Suppression Therapy

The American Society of Clinical Oncology has put forth guidelines for the treatment of premenopausal women with breast cancer. It’s important to note that these guidelines are suggestions based on the most recent research, but not absolute rules. There are many nuances when it comes to cancer that general guidelines do not take into account.

In general, premenopausal women who have stage II or stage III breast cancers for which chemotherapy is recommended should receive ovarian suppression therapy. The treatment should also be offered to some women with stage I breast cancer who have a greater risk of recurrence .

In contrast, women with stage I breast cancers for which chemotherapy is not recommended, or who have tumors that are node-negative and 1 centimeter or less in diameter should not receive ovarian suppression therapy.

For those who have a high risk of recurrence, for example, women with lymph node positive or larger tumors, the use of an aromatase inhibitor may be considered over tamoxifen because of further reduction in recurrence risk.

Before beginning an aromatase inhibitor, however, women should have an ultra-sensitive estradiol blood test to make sure they are postmenopausal, and this should be repeated periodically unless permanent ovarian suppression via surgery is chosen.

What Types Of Cancer Is Hormonal Therapy Used For

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  • Breast cancer: An estimated 80% of breast cancers are hormone-sensitive , which means they are fueled by hormones. More specifically, these are called estrogen-receptor-positive or progesterone-receptor-positive breast cancers. These terms mean this particular cancer has estrogen and/or progesterone receptors, which invite hormones to bind to them. Hormone-receptor-negative cancers are not influenced by hormones.
  • Prostate cancer: Most prostate cancers are stimulated by male sex hormones called androgens, says Dr. Leapman this is why urologists also refer to this treatment as androgen deprivation therapy. These hormones are made in the adrenal glands and testicles. Hormonal therapy for prostate cancer is used in several ways, including as short-term therapy for men prior to and during radiation therapy, as well as for men with advanced or metastatic cancer.

Hormonal therapy is sometimes used to destroy hormone-sensitive cancer cells that have spread to other parts of the body or those that have returned .

Hormonal therapy can also be used to ease a cancer patients symptoms . This is especially helpful for patients who are not able to have surgery or radiotherapy because of other health concerns.

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Drugs That Stop Androgens From Working

Anti-androgens

For most prostate cancer cells to grow, androgens have to attach to a protein in the prostate cancer cell called an androgen receptor. Anti-androgens are drugs that also connect to these receptors, keeping the androgens from causing tumor growth. Anti-androgens are also sometimes called androgen receptor antagonists.

Drugs of this type include:

They are taken daily as pills.

In the United States, anti-androgens are not often used by themselves:

  • An anti-androgen may be added to treatment if orchiectomy or an LHRH agonist or antagonist is no longer working by itself.
  • An anti-androgen is also sometimes given for a few weeks when an LHRH agonist is first started. This can help prevent a tumor flare.
  • An anti-androgen can also be combined with orchiectomy or an LHRH agonist as first-line hormone therapy. This is called combined androgen blockade . There is still some debate as to whether CAB is more effective in this setting than using orchiectomy or an LHRH agonist alone. If there is a benefit, it appears to be small.
  • In some men, if an anti-androgen is no longer working, simply stopping the anti-androgen can cause the cancer to stop growing for a short time. This is called the anti-androgen withdrawal effect, although it is not clear why it happens.

Newer anti-androgens

Enzalutamide , apalutamide and darolutamide are newer types of anti-androgens. They can sometimes be helpful even when older anti-androgens are not.

These drugs are taken as pills each day.

Joint And Muscle Pain

Joint pain and muscle pain are common side effects of aromatase inhibitors . The pain may be in the hands and wrists, feet and ankles, knees, back or other parts of the body. Joint and muscle pain are most common after youve been sleeping or inactive.

Almost half of women taking aromatase inhibitors have joint pain and about 15 percent have muscle pain .

Joint and muscle pain can mimic carpal tunnel syndrome. In rare cases, aromatase inhibitors can cause carpal tunnel syndrome .

Although aromatase inhibitors can cause joint and muscle pain, they dont cause permanent joint or muscle damage.

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What Is Intermittent Adt

Researchers have investigated whether a technique called intermittent androgen deprivation can delay the development of hormone resistance. With intermittent androgen deprivation, hormone therapy is given in cycles with breaks between drug administrations, rather than continuously. An additional potential benefit of this approach is that the temporary break from the side effects of hormone therapy may improve a mans quality of life.

Randomized clinical trials have shown similar overall survival with continuous ADT or intermittent ADT among men with metastatic or recurrent prostate cancer, with a reduction in some side effects for intermittent ADT .

How Often Is Ovarian Suppression Therapy Used

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Knowing that ovarian suppression therapy has benefits for some premenopausal women with breast cancer, you may be wondering how often this therapy is used. A 2019 study found that the use of ovarian suppression therapy has been increasing since 2014, and roughly 25% of women overall received ovarian suppression in addition to hormonal therapy.

Among those who received ovarian suppression, more than 30% chose an aromatase inhibitor in combination rather than tamoxifen. This study also found a survival benefit associated with ovarian suppression.

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Ovarian Suppression: Tamoxifen Vs An Aromatase Inhibitor

For women who are premenopausal, tamoxifen must be used rather than an aromatase inhibitor unless ovarian suppression therapy is used. Tamoxifen works by binding to estrogen receptors on breast cancer cells so that estrogen cannot bind .

Aromatase inhibitors, in contrast, work by blocking the conversion of androgens in the adrenal glands to estrogen . Before menopause, the greatest source of estrogen in the body is the ovaries, whereas after menopause, it is from this peripheral conversion of androgens.

Ovarian suppression therapy, by inducing menopause, allows premenopausal women to thus take an aromatase inhibitor. In postmenopausal women, it appears that aromatase inhibitors are 30% more effective in preventing breast cancer recurrence after five years relative to tamoxifen and decrease the risk of death by 15% after five years.

Studies are suggesting that an aromatase inhibitor may also be preferable to tamoxifen in high-risk premenopausal women. In addition, there are several drug interactions with tamoxifen that may make taking the medication challenging for some women.

Current aromatase inhibitors include:

The benefit of combining ovarian suppression therapy with either tamoxifen or an aromatase inhibitor depends on the stage of the tumor as well as a few other characteristics.

When During Cancer Treatment Is Hormonal Therapy Given

Hormonal therapy is often given in conjunction with other treatments. The timing varies depending on the tumor, its stage and its location, among other factors:

  • Neoadjuvant hormonal therapy is when hormones are given before surgery or radiotherapy. The goal is to make a tumor shrink, so its smaller, which can make it easier to treat.
  • Adjuvant hormonal therapy is given after the patient has received surgery, radiation therapy or chemotherapy. Given after treatment, hormones decrease the risk of cancer recurring or spreading.

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Hormone Therapy Has A Bigger Impact Than Chemotherapy On Womens Quality Of Life

Cellules cancéreuses. Expression de la protéine PML en rouge et du gène ZNF703 en vert dans des cellules de la lignée de cancer du sein MCF7. ©Inserm/Ginestier, Christophe

Analysis of the CANTO cohort published in the journal Annals of Oncology will upset received wisdom on the effects that hormone therapy and chemotherapy have on the quality of life in women with breast cancer. Contrary to the commonly held view, 2 years after diagnosis, hormone therapy, a highly effective breast cancer treatment worsens quality of life to a greater extent and for a longer time, especially in menopausal patients. The deleterious effects of chemotherapy are more transient. Given that current international guidelines recommend the prescription of hormone therapy for 5 to 10 years, it is important to offer treatment to women who develop severe symptoms due to hormone antagonist medication and to identify those who might benefit from less prolonged or intensive treatment strategies.

This work was directed by Dr Inès Vaz-Luis, specialist breast cancer oncologist and researcher at Gustave Roussy in the lab Predictive Biomarkers and Novel Therapeutic Strategies in Oncology .

Effectiveness For Metastatic Breast Cancer

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When evaluating potential treatments for metastatic breast cancer, it’s important to know that the goals of therapy are different than with early stage cancers. With early stage breast cancer, the goal is ultimately a cure . Metastatic breast cancer is, at this time, incurable. For this reason, the goal of treatment is to extend survival and improve or maintain quality of life.

For premenopausal women, the effectiveness of ovarian suppression therapy must be weighed against any side effects that lessen quality of life.

An older review of premenopausal women with breast cancer found that combining ovarian suppression therapy with tamoxifen improved overall survival. Given the advantage of an aromatase inhibitor over tamoxifen in early stage breast cancer, this may be beneficial as well.

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How Will I Know That My Hormone Therapy Is Working

Doctors cannot predict how long hormone therapy will be effective in suppressing the growth of any individual mans prostate cancer. Therefore, men who take hormone therapy for more than a few months are regularly tested to determine the level of PSA in their blood. An increase in PSA level may indicate that a mans cancer has started growing again. A PSA level that continues to increase while hormone therapy is successfully keeping androgen levels extremely low is an indicator that a mans prostate cancer has become resistant to the hormone therapy that is currently being used.

Medical Ovarian Suppression Therapy

Ovarian suppression can also be accomplished by interfering with the signals from the pituitary/hypothalamus that tell the ovaries to secrete estrogen. Hormones given once a month by injection lead to less secretion of gonadotropins by the pituitary gland .

This reduced release of luteinizing hormone and follicle-stimulating hormone by the pituitary gland decreases signals to the ovaries to produce estrogen and progesterone. Without this stimulation, the ovaries essentially go dormant.

Medications called gonadotropin hormone agonists include:

  • Trelstar, Decapeptyl Depot, or Ipssen

GnRH agonists are given by injection either every month or every three months, but when they are discontinued, the ovarian suppression is reversible.

A different GNRH agonist, Firmagon, is also being evaluated in clinical trials. Since conventional GnRH agonists may not maintain suppression in some people , especially when combined with an aromatase inhibitor, other options are being evaluated.

A clinical trial found that, when combined with the aromatase inhibitor letrozol, Firmagon resulted in a more rapid response that was maintained after cycle one. In contrast, triptorelin did not adequately maintain ovarian suppression in 15.4% of people using the injection.

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Side Effects Of Hormonal Therapy

Side effects can happen with any type of treatment for cancer, but everyones experience is different. Some people have many side effects. Other people have few or none at all.

If you develop side effects, they can happen any time during, immediately after or a few days or weeks after hormonal therapy. Sometimes late side effects develop months or years after hormonal therapy. Most side effects go away on their own or can be treated, but some side effects may last a long time or become permanent.

Side effects of hormonal therapy will depend mainly on the type of hormonal therapy, the dose of a drug or combination of drugs and your overall health.

It is important to report side effects and your concerns about side effects to the healthcare team. Doctors may measure how severe certain side effects are. Sometimes hormonal drug therapy may need to be adjusted if side effects are severe.

The following are the most common side effects that people tend to experience with hormonal therapy.

How Is Hormone Therapy Used To Treat Breast Cancer

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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 approved for adjuvant hormone treatment of premenopausal and postmenopausal women with ER-positive early-stage breast cancer, and the aromatase inhibitorsanastrozole, letrozole, and exemestane are approved for this use in postmenopausal women.

Research has shown that women who receive at least 5 years of adjuvant therapy with tamoxifen after having surgery for early-stage ER-positive breast cancer have reduced risks of breast cancer recurrence, including a new breast cancer in the other breast, and reduced risk of death at 15 years .

Until recently, most women who received adjuvant hormone therapy to reduce the chance of a breast cancer recurrence took tamoxifen every day for 5 years. However, with the introduction of newer hormone therapies , some of which have been compared with tamoxifen in clinical trials, additional approaches to hormone therapy have become common .

Some premenopausal women with early-stage ER-positive breast cancer may have ovarian suppression plus an aromatase inhibitor, which was found to have higher rates of freedom from recurrence than ovarian suppression plus tamoxifen or tamoxifen alone .

Men with early-stage ER-positive breast cancer who receive adjuvant therapy are usually treated first with tamoxifen. Those treated with an aromatase inhibitor usually also take a GnRH agonist.

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