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 main source of estrogen in premenopausal women, estrogen levels in these women can be reduced by eliminating or suppressing ovarian function. Blocking ovarian function is called ovarian ablation.
Ovarian ablation can be done surgically in an operation to remove the ovaries or by treatment with radiation. This type of ovarian ablation is usually permanent.
Alternatively, ovarian function can be suppressed temporarily by treatment with drugs called gonadotropin-releasing hormone agonists, which are also known as luteinizing hormone-releasing hormone agonists. By mimicking GnRH, these medicines interfere with signals that stimulate the ovaries to produce estrogen.
Estrogen and progesterone production in premenopausal women. Drawing shows that in premenopausal women, estrogen and progesterone production by the ovaries is regulated by luteinizing hormone and luteinizing hormone-releasing hormone . The hypothalamus releases LHRH, which then causes the pituitary gland to make and secrete LH and follicle-stimulating hormone . LH and FSH cause the ovaries to make estrogen and progesterone, which act on the endometrium .
Examples of ovarian suppression drugs are goserelin and leuprolide .
Blocking estrogens effects: Several types of drugs interfere with estrogens ability to stimulate the growth of breast cancer cells:
What Are The Side Effects Of Hormone Therapy
The side effects of hormone therapy depend largely on the specific drug or the type of treatment . The benefits and harms of taking hormone therapy should be carefully weighed for each person. A common switching strategy used for adjuvant therapy, in which patients take tamoxifen for 2 or 3 years, followed by an aromatase inhibitor for 2 or 3 years, may yield the best balance of benefits and harms of these two types of hormone therapy .
Hot flashes, night sweats, and vaginal dryness are common side effects of all hormone therapies. Hormone therapy also may disrupt the menstrual cycle in premenopausal women.
Less common but serious side effects of hormone therapy drugs are listed below.
Tamoxifen
- breathing problems, including painful breathing, shortness of breath, and cough
- loss of appetite
Alternatives To Hrt For Protecting Your Bones From Osteoporosis
HRT is no longer recommended for treatment of osteoporosis due to its risks and available alternative options. Bisphosphonate medications are generally recommended to treat osteoporosis instead. Other medications that may be considered are teriparatide, denosumab, or selective estrogen receptor modulators . SERMs are a newer class of drugs, similar to estrogen, that protect against osteoporosis by increasing bone density, while also protecting against the development of breast cancer.
Evista is a widely used SERM that has been shown to increase bone growth and density and reduce the risk of breast cancer. Unfortunately, it does not relieve symptoms of menopause such as hot flashes and may actually worsen them. It is primarily used in women who are at high risk for developing breast cancer or for those who cannot tolerate other medications used to treat osteoporosis.
Additional steps you can take to prevent and/or treat osteoporosis include:
- Performing weight-bearing exercises
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Heart Disease And Strokes
HRT does not significantly increase the risk of cardiovascular disease when started before 60 years of age, and may reduce your risk.
Taking HRT tablets is associated with a small increase in the risk of stroke, but the risk of stroke for women under age 60 is generally very low, so the overall risk is still small.
Page last reviewed: 09 September 2019 Next review due: 09 September 2022
You May Be Interested To Read
A large-scale study of HRT and the risk of breast cancer: Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. The Lancet 2003 362:9382
Menopause: diagnosis and management – National Institute for Health and Care Excellence guidance on diagnosing and managing menopause.
HRT and breast cancer risk: a blog post from the ICR discussing what research about HRT and breast cancer means for women.
Further information on the Breast Cancer Now Generations Study.
Funding: This work is partially funded by the NIHR School for Primary Care Research and by Cancer Research UK through its Oxford Centre.
Conflicts of Interest: The study authors declare no conflicts of interest.
Disclaimer: NIHR Alerts are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that views expressed in NIHR Alerts are those of the author and reviewer and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
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Weighing The Risks And Benefits
The findings came as no surprise to Dr. Otis Brawley, Bloomberg distinguished professor of oncology and epidemiology at Johns Hopkins University in Baltimore, who was not involved in the new research.
For 18 years now I have been trying to convince women that they dont want to start postmenopausal estrogens, and Ive been encouraging women who have hot flashes to try to resolve those hot flashes through other medical means, Brawley said.
Now theres some women who have hot flashes that are so significant that giving them estrogen actually is worth the risk, he said. Virtually everything we do in medicine has a risk and a benefit to it, and when the benefit starts getting to be clearly higher than the risk then perhaps you ought to do it, but when the benefit is not clearly higher than the risk, I try to avoid using it.
In general, the US Food and Drug Administration says not to take hormone therapy if you have problems with vaginal bleeding have or had a history of certain cancers have or had a blood clot, stroke or heart attack or have a bleeding disorder, liver disease or allergic reactions to hormone medicine.
For women who are already taking a hormone replacement therapy and might have some concerns, Brawley said to talk to your doctor.
Hormonal Therapies For Breast Cancer
Hormonal therapy is used to treat breast cancers that are hormone receptor positive. These cancers have receptors for the hormones oestrogen and/or progesterone they are called ER and/or PR positive cancer. Around 70% of breast cancers are ER positive.
Hormonal therapy may be recommended after other treatments for breast cancer like surgery, chemotherapy or radiotherapy. Sometimes it is used to shrink breast cancer before other treatment is given. The aim of hormonal therapy is to starve breast cancer cells of the hormone that makes them grow. This lowers the risk of breast cancer coming back or a new breast cancer developing in the treated breast or in the other breast.
There are several different types of hormonal therapies. Some are taken as tablets and others may involve surgery, injections or radiotherapy to turn off ovaries in premenopausal women.
This brochure explains the following types of hormonal therapies to turn off ovaries in premenopausal women:
Hormonal therapies can also be used to treat ductal carcinoma in situ and to reduce the risk of breast cancer in women with a strong family history or other risk factors for breast cancer.
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Strengths And Weaknesses Of This Study
Some limitations of this study arise from inevitable shortfalls in completeness and accuracy within any routinely collected dataset. A small proportion of women had missing information on smoking status, alcohol consumption, and BMI, but these were dealt with by multiple imputation. As we did not have reliable data for age at onset of menopause for all women, we estimated onset from the first menopause specific record before the earliest HRT prescription. For women with no such record we assumed onset within the most common age range of 50 to 54 years. We did not investigate the differences between continuous and sequential HRT because these regimens are prescribed at different times after menopause. As our cases and controls were matched by age, they would likely have been prescribed similar regimens, making a comparison infeasible. Our primary focus, anyway, was recent long term exposure.
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 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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Possible Side Effects Of Hormone Therapy
Some side effects are common to all methods of hormone therapy and are due to the reduced levels of oestrogen.
These include:
- Mood changes.
Tamoxifen and aromatase inhibitors also produce some different side effects. You may experience some of the side effects listed, but are unlikely to experience them all.
For most people who are recommended to take hormone therapy for breast cancer, the risks of treatment are outweighed by the benefits.
Here is a list of possible side effects that might be experienced on tamoxifen and aromatase inhibitors:
| Tamoxifen |
Turning Off The Ovaries With Medication
The ovaries can be shut down temporarily with medication. This is usually done by giving a course of monthly injections of goserelin . This gradually causes the levels of oestrogen to fall, which leads to temporary menopause.The menstrual periods stop and other symptoms of menopause may develop . These symptoms can be reversed. If the injections are stopped, the oestrogen levels and menstrual periods return to normal. Some women who are considering having their ovaries removed have these injections for a few months to test out the menopausal symptoms. They still have the choice of reversing the effect if the side effects are too intense. The use of goserelin is strictly controlled by the Australian Pharmaceutical Benefits Scheme and may not be available to all women.
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Implications For Clinicians And Policymakers
This study delivers more generalisable estimates of the different risks of breast cancer associated with specific progestogen components of HRT, while confirming no increased risks from short term use of oestrogen only, estradiol-dydrogesterone, and tibolone. Increasing duration of use was generally associated with increased risk, with tibolone and estradiol-dydrogesterone showing the smallest risks. The frequency of prescribing for treatments including dydrogesterone was, however, much lower than for those including norethisterone, medroxyprogesterone, or levonorgestrel.
Stopping The Ovaries Working
In premenopausal women, doctors might use a type of hormone treatment to stop the ovaries from producing oestrogen. This type of drug is called a luteinising hormone releasing hormone . For example, goserelin and leuprorelin . You might have this on its own or with other hormone therapy drugs.
LHRH drugs work by blocking a hormone made in the pituitary gland that stimulates your ovaries to make and release oestrogen. This stops your ovaries from working. So you won’t have periods or release eggs while you are having the injections.
When you stop taking the drug, your ovaries should start working again. But, if you’re close to the age at which your menopause would naturally start, your periods might not start again.
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Can Hormone Therapy Be Used To Prevent Breast Cancer
Yes. Most breast cancers are ER positive, and clinical trials have tested whether hormone therapy can be used to prevent breast cancer in women who are at increased risk of developing the disease.
A large NCI-sponsored randomized clinical trial called the Breast Cancer Prevention Trial found that tamoxifen, taken for 5 years, reduces the risk of developing invasive breast cancer by about 50% in postmenopausal women who were at increased risk . Long-term follow-up of another randomized trial, the International Breast Cancer Intervention Study I, found that 5 years of tamoxifen treatment reduces the incidence of breast cancer for at least 20 years . A subsequent large randomized trial, the Study of Tamoxifen and Raloxifene, which was also sponsored by NCI, found that 5 years of raloxifene reduces breast cancer risk in such women by about 38% .
As a result of these trials, both tamoxifen and raloxifene have been approved by the FDA to reduce the risk of developing breast cancer in women at high risk of the disease. Tamoxifen is approved for this use regardless of menopausal status. Raloxifene is approved for use only in postmenopausal women.
Why Does Hrt Increase Breast Cancer Risk
Its not fully understood why HRT increases the risk of breast cancer, but research suggests that this is due to the higher levels of oestrogen. Some breast cancers can use oestrogen to help them to grow.
There are some factors that can influence the risk of breast cancer.
- How long you take HRT for. The longer you use HRT, the greater the risk
- The type of HRT you are taking. Breast cancer risk is greater with combined HRT than with oestrogen-only HRT
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Hormone Replacement Therapy Does Not Increase Breast Cancer Recurrence Mortality In Survivors
An analysis of data from more than 8400 postmenopausal women with a history of early-stage nonmetastatic, ER-positive breast cancer suggests there was no increase in risk of breast cancer recurrence or mortality observed with use of vaginal estrogen therapy or menopausal hormone therapy.
Undergoing hormone replacement therapy for menopausal symptoms does not increase the risk of breast cancer recurrence in women treated for breast cancer, according to a new study of more than 8000 women.
An analysis of longitudinal data from a national cohort of postmenopausal women diagnosed with early-stage invasive estrogen receptor positive nonmetastatic breast cancer who received no treatment or 5 years of adjuvant endocrine therapy, results of the analysis suggests there was no statistically significant increase in the risk of recurrence or mortality for those who received either vaginal estrogen therapy or menopausal hormone therapy.
In postmenopausal women treated for early-stage ER-positive breast cancer, use of vaginal estrogen therapy or menopausal hormone therapy was not associated with increased risk of recurrence or mortality. In patients treated with vaginal estrogen therapy and adjuvant aromatase inhibitors, we observed an increased risk of recurrence but not mortality. This association was not observed among women who received tamoxifen or in those who did not receive adjuvant endocrine therapy, wrote investigators.
Do The Benefits Of Hrt Outweigh The Risk
Hormone replacement therapy is an effective treatment for relieving hot flashes from menopause. But the known link between hormone therapy and increased breast cancer among risks has discouraged many women and their doctors from choosing or recommending this treatment.
The type of hormone therapy , as well as the woman’s individual characteristics, risk factors, and severity of menopause symptoms, should be considered when weighing the risks and benefits of HRT. The decision to use hormone therapy after menopause should be made by a woman and their health care provider after weighing all of the potential risks and benefits .
The known association between HRT and breast cancer has prevented many breast specialists from recommending it for breast cancer survivors. Unfortunately, many women experience menopause symptoms after breast cancer treatment. Some forms of chemotherapy may also cause early menopause in premenopausal women.
In the past, doctors may have offered HRT after breast cancer treatment because there weren’t clearcut studies showing any harm. However, early in 2004, a study was stopped early after showing that cancer survivors on HRT were more likely to develop a new or recurrent breast cancer. Doctors now feel it is too risky to treat breast cancer survivors with HRT.
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What Are The Risks Of Hrt
Breast cancer risk differs depending on the type of HRT and a womans personal history of breast cancer.
Based on results from the very large Womens HealthInitiative studies, combination HRT increases breast cancer risk and this increase in risk lasted for more than 10 years after the women stopped taking HRT.
Higher-dose combination HRT increases breast cancer risk more than lower-dose combination HRT.
Combination HRT also increases the likelihood that the cancer may be found at a more advanced stage. Combination HRT is linked to increased breast density, which can make it harder for mammograms to detect breast cancer.
Breast cancer risk appears to be higher with daily progesterone than with less frequent progesterone .
This increase in risk applies to bioidentical and natural hormone products as well as synthetic hormones. Bioidentical means the hormones in the product are identical to the hormones your body produces. Bioidentical hormones are derived from plants, so theyre sometimes called natural. Synthetic hormones are made in a lab and are also chemically identical to thehormones in your body. It’s important to know that many herbal and bioidentical HRT products fall outside the jurisdiction of the United States Food and Drug Administration and so aren’t subject to the same regulations and testing that medicines are.