Hormones And Breast Cancer
The hormones estrogen and progesterone make some breast cancers grow. They are called hormone-sensitive breast cancers. Most breast cancers are sensitive to hormones.
Estrogen and progesterone are produced in the ovaries and other tissues such as fat and skin. After menopause, the ovaries stop producing these hormones. But the body continues to make a small amount.
Hormone therapy only works on hormone-sensitive cancers. To see if hormone therapy may work, doctors test a sample of the tumor that has been removed during surgery to see if the cancer might be sensitive to hormones.
Hormone therapy can work in two ways:
What Are Hormone Receptors
Breast cancers that are hormone receptor positive have receptors for the female hormones oestrogen and/or progesterone on the inside of the cancer cells.
In breast cancer cells that are hormone receptor positive, oestrogen and/or progesterone, which are naturally produced in the body, make the cancer grow. You can think of it as the receptor being the lock and oestrogen being the key. The oestrogen fits into the receptor and switches the cancer cell on, causing it to grow. Hormone therapy for breast cancer can starve cancer cells by upsetting this process.
Testing for hormone receptors is part of the routine pathology testing following surgery. Testing is done on a core biopsy sample if surgery is not planned.
Your doctor will be able to tell you if your breast cancer is hormone receptor positive or not. Most, but not all breast cancer is hormone receptor positive.
The hormonal therapies described in this brochure only work against breast cancers that are hormone receptor positive. Other treatments need to be used for cancers that are hormone receptor negative.
Managing Symptoms & Side Effects
General side effects can happen when hormonal therapy is given, but they depend on a number of things, including the specific cancer being treated, how your body responds to the treatment and the type of hormonal therapy being administered. Side effects vary between men and women and by drug. Some of the most common side effects include:
- loss of interest in sex
We offer ways for you to document, track, recognize and reduce your symptoms and side effects. Even with all these resources available, we want to remind you that its still important to discuss your symptoms with your healthcare team.
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Aromatase Inhibitors And Treatment For Early And Locally Advanced Breast Cancers
For women with hormone receptor-positive breast cancer, treatment with an aromatase inhibitor lowers the risk of :
- Breast cancer in the opposite breast
- Death from breast cancer
Among postmenopausal women with hormone receptor-positive breast cancer, aromatase inhibitors offer the same or slightly greater benefit compared to tamoxifen alone .
Anastrozole, exemestane and letrozole are equally effective and have similar side effects . However, you may tolerate one drug better than another.
Learn about aromatase inhibitors and treatment for metastatic breast cancer.
For a summary of research studies on aromatase inhibitors and early breast cancer, visit the Breast Cancer Research Studies section.
Targeted Drug Therapy For Breast Cancer
Targeted drug therapy uses medicines that are directed at proteins on breast cancer cells that help them grow, spread, and live longer. Targeted drugs work to destroy cancer cells or slow down their growth. They have side effects different from chemotherapy and can be given in the vein , as an injection under the skin, or as a pill.
Some targeted therapy drugs, for example, monoclonal antibodies, work in more than one way to control cancer cells and may also be considered immunotherapy because they boost the immune system.
Like chemotherapy, these drugs enter the bloodstream and reach almost all areas of the body, which makes them useful against cancers that have spread to distant parts of the body. Targeted drugs sometimes work even when chemo drugs do not. Some targeted drugs can help other types of treatment work better.
Several types of targeted therapy drugs can be used to treat breast cancer.
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How Are Aromatase Inhibitors Taken
Aromatase inhibitors are pills. You take one pill every day.
Postmenopausal women with hormone receptor-positive breast cancer can:
- Begin hormone therapy with an aromatase inhibitor
- Begin hormone therapy with tamoxifen and then after a few years, switch to an aromatase inhibitor
When an aromatase inhibitor is the only hormone therapy given, its taken for 5-10 years.
When an aromatase inhibitor is taken after tamoxifen, the drugs are taken for a combined total of 5-10 years.
Talk with your health care provider about how long you should take an aromatase inhibitor.
Find a list of questions on hormone therapy you may want to ask your health care provider.
Drugs That Block Estrogen
Some drugs work by blocking estrogen from causing cancer cells to grow.
Tamoxifen is a drug that prevents estrogen from telling cancer cells to grow. It has a number of benefits:
- Taking Tamoxifen for 5 years after breast cancer surgery cuts the chance of cancer coming back by half. Some studies show that taking it for 10 years may work even better.
- It reduces the risk that cancer will grow in the other breast.
- It slows the growth and shrinks cancer that has spread.
- It reduces the risk of getting cancer in women who are at high risk.
Other drugs that work in a similar way are used to treat advanced cancer that has spread:
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If Cancer Has Come Back Or Spread
Hormone therapy can be used to treat breast cancer that has come back or that has spread to another part of the body .
Its given either alone or with other treatments, depending on what treatments you had before.
If your breast cancer came back during or after treatment with hormone therapy, you may be offered a different type of hormone therapy.
Endocrine Therapy For Hormone Receptor
Background: Clinical guidelines generally recommend endocrine therapy as first-line treatment of hormone receptor-positive advanced breast cancer whereas chemotherapy should be considered in the presence of life-threatening disease or limited clinical benefit after three sequential ET regimens. However, it is unclear if real-world clinical practice is in accordance with the current guidelines. This study was to present the real-world treatment patterns and ET regimens among HR+ ABC patients in China.
Methods: Using data from the Nation-wide Multicenter Retrospective Clinical Epidemiology Study of Female Advanced Breast Cancer in China , we investigated the clinicopathological characteristics, clinical profiles, and treatment patterns of HR+ ABC patients from January 2012 to December 2014.
Less than one quarter of patients initiated palliative ET for HR+ ABC in routine clinical practice. Patients who received multi-lines of ET experienced successive shorter durations following each line of therapy. This real-life data provides a solid overview of ET for HR+ ABC from China, indicating unmet need for treatment options that improve the effectiveness of endocrine therapy.
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Drug Shows Promise In Overcoming Endocrine Therapy Resistance In Breast Cancer
DALLAS Nov. 15, 2022 For patients with estrogen receptor -positive breast cancer, development of the so-called Y537S mutation signals that their disease has taken an aggressive course and may become resistant to endocrine therapy. Now a preclinical study, led by researchers at UT Southwestern Medical Center, suggests that a class of new drugs already in clinical trials might work especially well in breast cancer patients who have acquired this mutation.
Identifying drugs that selectively target this highly aggressive mutation has been elusive, said Prasanna Alluri, M.D., Ph.D., Assistant Professor of Radiation Oncology, a member of UTSWs Harold C. Simmons Comprehensive Cancer Center, and senior author of the study published in JCI Insight. Now we have uncovered a new therapeutic vulnerability in breast cancers that have developed resistance to endocrine therapy through acquisition of the Y537S mutation. When used early, this drug may prevent or delay development of endocrine therapy resistance by blocking an increase in the proportion of cells harboring the Y537S mutation.
In the U.S., over 250,000 patients are diagnosed with breast cancer each year. About 75% of breast cancers are ER-positive, meaning that the growth of these tumor cells is fueled by the binding of estrogen to the estrogen receptor protein in the cytoplasm. This binding results in the ER protein entering the nucleus and altering the on/off status of many genes, stimulating growth of the tumor.
Why Is Knowing Hormone Receptor Status Important
Knowing the hormone receptor status of your cancer helps doctors decide how to treat it. If your cancer has one or both of these hormone receptors, hormone therapy drugs can be used to either lower estrogen levels or stop estrogen from acting on breast cancer cells. This kind of treatment is helpful for hormone receptor-positive breast cancers, but it doesnt work on tumors that are hormone receptor-negative .
All invasive breast cancers should be tested for both of these hormone receptors either on the biopsy sample or when the tumor is removed with surgery. About 3 of 4 breast cancers have at least one of these receptors. This percentage is higher in older women than in younger women. DCIS should also be checked for hormone receptors.
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Who Gets Hormone Therapy For Breast Cancer
When youÃ¢re diagnosed with breast cancer, your doctor will test cells from your tumor to see if they have parts on their surfaces called receptors that use estrogen or progesterone. If they do, it means that they depend on these hormones to grow. In that case, your doctor will probably recommend hormone therapy as part of your treatment plan.
If youÃ¢ve already been treated for breast cancer, you might use hormone therapy to help keep it from coming back. It also helps lower your odds of getting new cancers in the other breast.
Also, if you donât have the disease but have a family history of it, or genes that raise your risk, your doctor may recommend hormone therapy to lower your chances of getting it.
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Cefficacy End Points For Regular Approval Of Cancer Drugs
Sponsors must first select the primary clinical end point. The end point must reliably measure clinical benefit, and trial design should minimize bias. Blinding of randomized trials is the most reliable method to prevent bias. The common stance that oncology trials cannot be blinded should be carefully evaluated because blinding allows additional end points to be used, such as tumor-related symptoms, and enhances the credibility of end points like TTP.
The law requires demonstration of clinical benefit for drug approval. Clinical benefit can be defined as treatment effects judged to be clinically meaningful and suitable as the primary efficacy endpoint for regular drug approval. In oncology, the most reliable end point is survival. However, the FDA also considers other end points to represent clinical benefit in cancer patients. In the following subsections, several non-survival end points are described which have supported cancer drug approval.
Additional information on trial designs and results from trials supporting approval of cancer drugs can be found in the Clinical Trials Section of approved package inserts, in transcripts from meetings of the ODAC , and in FDA guidance documents .
1Regular Approval, RR, and TTP
TABLE 11.4. End Points for Regular Approval of Cancer Drugs*
- Based on applications approved by CDER’s DODP from 19902002.
2Regular Approval, Quality of Life , and Patient Reported Outcomes
3Composite Clinical Benefit End Points
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Is Estrogen A Cause Of Breast Cancer
While the link between estrogen and breast and ovarian cancer in women has been known for many years, its been unclear if there is a link between male breast cancer and estrogen. Now an international study has found that men with naturally high levels of estrogen may have a higher-than-average risk of breast cancer.
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.
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:
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Having Hormonal Therapy For Breast Cancer
Hormonal therapy drugs reduce the risk of breast cancer coming back. It is important to take it for as long as you have been prescribed it for. Try to make taking it part of your daily routine so it becomes a habit.
Most women cope well with the side effects of hormonal therapy. They may be more of a problem in the first few months, but usually get better over time. If the side effects do not improve or are difficult to cope with, talk to your specialist nurse or cancer doctor. They can prescribe drugs to help and suggest ways of coping.
If you are still having problems after this, then your cancer doctor may suggest changing to a different type of hormonal therapy.
Tamoxifen And Breast Cancer Prevention
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 .
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Endocrine Therapy For Postmenopausal Women
Postmenopausal women with hormone receptor positive breast cancer may be offered adjuvant therapy with either tamoxifen or with an aromatase inhibitor. Aromatase inhibitors belong to a class of drugs that work by reducing the levels of estrogen in the body. Even if you have stopped menstruating, your body may still produce small amounts of estrogen in the adrenal glands, fat tissue and even breast tissue. These drugs first became available in the mid-to-late 1990s and have been shown to reduce the risk of breast cancer recurrence in postmenopausal women with early stage breast cancer. Such drugs include anastrozole , exemestane and letrozole .
Postmenopausal women with hormone-positive tumors may do just as well or perhaps a bit better with an aromatase inhibitor when compared to tamoxifen. It is not recommended for these women to undergo ovarian suppression as adjuvant treatment since their ovaries are not producing estrogen. Oophorectomy would be considered in this case in women who are BRCA 1 or 2 mutation carriers or have a strong family history of ovarian cancer as a preventive measure.
Endocrine therapy may be considered to reduce the risk of future breast cancer in hormone receptor-positive DCIS.
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:
- turning off or removing the ovaries
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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Treatments To Stop Ovarian Function In Premenopausal Women
Women who haven’t undergone menopause â either naturally or as a result of cancer treatment â may opt to undergo treatment to stop their ovaries from producing hormones.
Options may include:
- Surgery to remove the ovaries
- Radiation therapy aimed at the ovaries
- Medications, such as goserelin
Treatments to stop ovarian function may allow premenopausal women to take medications only available to postmenopausal women.
Data Collection And Quality Control
A questionnaire was designed to obtain demographic information and clinical variables, such as age at diagnosis, geographic region, histology grade, hormone receptor , human epidermal growth factor receptor 2 status, and treatment information including breast surgery, adjuvant therapy, targeted therapy, radiation therapy, and palliative systemic treatment.
All of the aforementioned information was extracted from medical charts to the designed case report form by trained doctors. Then, data was double-entered into computer-based database by two independent data input clerks. All completed databases were sent to CHCAMS for validation. Inconsistencies between the two databases were reported to the local doctors for revision until the databases were consistent. After that, one of the databases was selected to perform a final assessment with the original medical record, then 5% of the medical charts were sent to CHCAMS for quality control review.
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The Effects Of Serms And Serds On The Tumor Immune Microenvironment
SERMs and SERDs are currently the most important endocrine therapeutic regimens for BC. SERMs, represented by tamoxifen, toremifene and raloxifene, work through competitive blockage of the interaction between estrogen and ER. SERDs, such as fulvestrant, contribute to the downregulation and degradation of ER . Accumulating evidence from experimental and clinical studies has revealed the multifaceted immunomodulatory effects of SERMs and SERDs in particular, progress has been made to elaborate how SERMs and SERDs act upon the immune microenvironment of BC .
Table 1 The effects of different endocrine therapeutic strategies on immune cells
In addition to being effective for treating BC, tamoxifen and raloxifene have also been shown to reduce the risk of BC in highly susceptible women . Tamoxifen administration was found to upregulate IFN-related genes in normal human mammary epithelial cells from in vitro experiments, implying its positive effect on the immune surveillance of normal breast tissue . Moreover, tamoxifen and toremifene were also found to enhance TNF-R2 expression on activated T cells by inhibiting the activation of JNK and promoting TNF-R2-mediated T cell proliferation . These results might explain their BC-preventive effect.