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.
- Breathing problems, including painful breathing, shortness of breath, and cough
- Loss of appetite
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 7 of 10 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.
What Do Cell Receptors Do
Receptors are located on the outer surface of a cell, and they behave like little light switches for the cell. Those receptors can be activated, or turned on, when they bind to certain hormones or molecules in the body. This activation process tells the cancer cell to grow and multiply.
Breast cancer can have a few specific receptors that do this. After you have a biopsy of cancer cells, those cells can be tested for the presence of these receptors.
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Progesteronepr Signaling Klf5 And Breast Cancer
Progesterone is essential for normal postnatal mammary gland development during pregnancy and lactation by stimulating ductal side branching and development of lobuloalveolar structures . A recent study showed that progesterone promotes proliferation and activity of mammary stem cells . In addition, PR knockout mice showed incomplete mammary gland ductal side branching due to insufficient cell proliferation .
Accumulated evidence suggests that Pg and PR promote mammary tumorigenesis . Administration of medroxyprogesterone acetate, a synthesized progesterone, induces mammary ductal carcinomas with a mean latency of 52 weeks and an incidence of about 80% in BALB/c female mice . Moreover, Pg has been shown to increase breast cancer risk for menopausal women in several large-scale hormone-replacement therapy clinical studies . In these studies, Pg plus estrogen significantly increased the risk of invasive breast cancer compared with estrogen alone. Additionally, Pg has been shown to have proliferative effects in the PR-positive breast cancer cell lines in vitro and in nude mice . Importantly, Pg was shown to reprogram a small subset of ER +/PR +/cytokeratin 5 -differentiated luminal cells into ERPRCK5 + progenitor cancer cells .
Taken together, these findings suggest that KLF5 is an important downstream target gene of the PgPR signaling to regulate the development of normal breast and breast cancer.
Yikyung Park, in, 2019
What Do Estrogen Receptors Do
Estrogen receptors are receptors that are activated by the hormone estrogen . They are found most commonly in the inner lining of the uterus , breast cells, ovarian cells, and a part of the brain . In males, they are found in the ducts attached to the testes. Some have also been found in the kidney, brain, bone, heart, lungs, intestine, and prostate.
When estrogen and/or progesterone attach to their specific hormone receptors, they help contribute to the growth and function of breast cells. Estrogen and progesterone are female hormones playing a key role in the sexual and reproductive cycle of women. These hormones are also found in men but exist in smaller quantities.
The ER is also a target of growing interest to develop medicines for osteoporosis, breast cancer, and other endocrine female disorders.
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Triple Negative Breast Cancer
Triple negative breast cancers don’t have oestrogen receptors, progesterone receptors or HER2 receptors. Around 15 out of 100 women have this type . It is more common in younger women.
Hormone therapies and targeted cancer drugs do not work well for this type of breast cancer. So you are more likely to have chemotherapy.
What Is A Hormone Receptor
In breast cancer, hormone receptors are the proteins located in and around breast cells. These receptors signal cells both healthy and cancerous to grow. In the case of breast cancer, the hormone receptors tell the cancer cells to grow uncontrollably, and a tumor results.
Hormone receptors can interact with estrogen or progesterone. Estrogen receptors are the most common. This is why ER-positive is the most common form of breast cancer.
Some people are diagnosed with progesterone receptor-positive breast cancer. The key difference is whether cancerous cells are getting growth signals from estrogen or progesterone.
Testing for hormone receptors is important in treating breast cancer. In some cases, there are no hormone receptors present, so hormone therapy isnt a good treatment option. This is called hormone receptor-negative breast cancer.
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Progesterone Receptor: Historical Perspective
Like ER, PR status is an independent predictive factor for benefit from adjuvant endocrine therapy and a prognostic indicator for early recurrence in breast cancer.3436 This discovery was preceded by observations that a subset of ER-positive breast cancers failed to respond to hormonal manipulation, indicating that ER presence alone was not a sufficient indicator of hormone dependence in breast cancer. It was shown that ER-positive/PR-positive breast cancers fared better compared with ER-positive/PR-negative tumors to adjuvant treatment.37 Studies by Horowitz and associates, the same group that extensively studied ER, suggested that the presence of PR might serve as an indicator of the functionality of the estrogen signaling pathway in the breast.38
Ligand-binding assays were the gold standard for early characterization and measurement of PR.45 With the advent of monoclonal antibodies to PR, IHC largely replaced the biochemical assays for PR measurement in the mid-1990s.46
Several studies demonstrated that IHC was superior to ligand-binding assays and enzyme immunoassays for assessing ER and PR status in primary breast cancer and had equivalent or better ability to predict response to adjuvant endocrine therapy.4650 However, reproducible and reliable IHC assays are essential with proper standardization for meaningful clinical application.
Issam Makhoul, in, 2018
What Do The Results Mean
After testing, your doctor will be able to tell you which of the following categories best describes the breast cancer. Most breast cancers are hormone-receptor-positive.
- ER+: About 80% of breast cancers are estrogen-receptor positive.
- ER+/PR+: About 65% of estrogen-receptor-positive breast cancers are also progesterone-receptor-positive. This means that the cells have receptors for both hormones, which could be supporting the growth of the breast cancer.
- ER+/PR-: About 13% of breast cancers are estrogen-receptor-positive and progesterone-receptor-negative. This means that estrogen, but not progesterone, may be supporting the growth and spread of the cancer cells.
- ER-/PR+: About 2% of breast cancers are estrogen-receptor-negative and progesterone-receptor-positive. This means that the hormone progesterone is likely to support the growth of this cancer. Only a small number of breast cancers test negative for estrogen receptors but positive for progesterone receptors. More research is needed to better understand progesterone-receptor-positive breast cancers.
- ER-/PR-: If the breast cancer cells do not have receptors for either hormone, the cancer is considered estrogen-receptor-negative and progesterone-receptor-negative . About 25% of breast cancers fit into this category.
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Selective Estrogen Receptor Response Modulators
Selective estrogen receptor response modulators act as blockers on the breast cells. They attach to the estrogen receptors in breast cells. In this way, they stop estrogen from sending the signal to the cell to grow.
Examples of SERMs include:
- toremifene , for people with advanced ER-positive breast cancer after menopause
A doctor may prescribe one of these drugs alongside another option.
Possible adverse effects include:
- vaginal dryness or discharge
Taking additional medication may help reduce these effects.
Much less commonly, there may be a higher risk of uterine cancer, blood clots, deep vein thrombosis, pulmonary embolism, and stroke.
Hormone Receptor Positive Breast Cancer Status
As part of the staging process for confirmed breast cancer tumors, a pathological-histological evaluation of a biopsy sample will be conducted. In addition to visual features under the microscope, such as:-
- the shapes of the cells
- the cell formation
the pathologist will also test the tumor to determine the levels of expression for various hormones, proteins, and hormone receptors.
This process is typically undertaken through the injection of the tumor sample with dyes that react chemically with certain proteins contained in in the breast tumor.
Determining the hormone receptor status of a given breast cancer will give the doctors information on how fast the tumor is growing. Also, whether or not there is evidence of cell damage and death. In addition, doctors will determine the particular genetic type of cells which have become malignant. Finally, medics will try to determine how the breast carcinoma will likely respond to chemotherapy and endocrine therapy treatments.
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How It Affects Your Treatment
If you have an HR-positive breast cancer, your doctor may prescribe drugs that target certain hormones your body makes. Doing that makes it harder for cancer cells to survive.
There are different kinds of hormone treatments. Some lower the amount of those hormones that your body makes. Others block the effects of hormones in breast tissue or in other places where the cancer may have spread.
In general, the more receptors you have and the greater their intensity, the more likely it is that hormone treatments will work.
If your cancer is only âER-positiveâ or only âPR-positiveâ — not both — it may still respond to hormone treatments.
If your disease is both ER-negative and PR-negative, hormone therapy is unlikely to work. Another type of treatment may work better. Your doctor will find the best options with the fewest side effects and talk with you about the benefits and risks of each.
Are There Any Risks To The Test
You may have a little bruising or bleeding at the biopsy site. Sometimes the site gets infected. If that happens, you will be treated with antibiotics. A surgical biopsy may cause some additional pain and discomfort. Your health care provider may recommend or prescribe medicine to help you feel better.
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Predicting Endocrine Therapy Response
In the metastatic setting, a study by van Kruchten et al. assessed the predictive value of 18F-fluoroestradiol imaging for response to estradiol treatment, a therapeutic approach for extensively pretreated patients . Patients with acquired endocrine-resistant metastatic ER-positive breast cancer and progression after at least 2 lines of therapy underwent baseline 18F-fluoroestradiol PET/CT followed by estradiol treatment. For 15 evaluable patients, the positive predictive value was 60%, the negative predictive value was 80%, and the area under the curve was 0.62 using a median SUVmax cutoff of 1.5 for discriminating clinical benefit from progressive disease. The study highlighted the potential for 18F-fluoroestradiol imaging to identify patients with acquired endocrine resistance who are unlikely to benefit from estradiol therapy indicated by poor 18F-fluoroestradiol uptake. This study adds to landmark studies from Washington University and the University of Washington, which demonstrated a predictive value of 18F-fluoroestradiol imaging for endocrine therapy benefit .
Hormone Receptor Status And Early Breast Cancer Prognosis
Hormone receptor status is related to the risk of breast cancer recurrence.
Hormone receptor-positive tumors have a slightly lower risk of breast cancer recurrence than hormone receptor-negative tumors in the first 5 years after diagnosis .
After about 5 years, this difference begins to decrease and over time, goes away .
For a summary of research studies on hormone receptor status and survival, visit the Breast Cancer Research Studies section.
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Early Detection Of Breast Cancer
Breast cancer is one of a few cancers for which an effective screening test, mammography, is available. MRI and ultrasound are also used to detect breast cancer, but not as routine screening tools.
Ongoing studies are looking at ways to enhance current breast cancer screening options. Technological advances in imaging are creating new opportunities for improvements in both screening and early detection.
One new technology is 3-D mammography, also called breast tomosynthesis. This procedure takes images from different angles around the breast and builds them into a 3-D-like image. Although this technology is increasingly available in the clinic, it isnt known whether it is better than standard 2-D mammography, for detecting cancer at a less advanced stage.
NCI is funding a large-scale randomized breast screening trial, the Tomosynthesis Mammographic Imaging Screening Trial , to compare the number of advanced cancers detected in women screened for 5 years with 3-D mammography with the number detected in women screened with 2-D mammography.
For example, the Women Informed to Screen Depending on Measures of Risk study aims to determine if risk-based screeningthat is, screening at intervals that are based on each womans risk as determined by her genetic makeup, family history, and other risk factorsis as safe, effective, and accepted as standard annual screening mammography.
What Happens During Er/pr Testing
Your provider will need to take a sample of breast tissue in a procedure called a breast biopsy. There are three main types of breast biopsies:
- Fine needle aspiration biopsy, which uses a very thin needle to remove a sample of breast cells or fluid
- Core needle biopsy, which uses a larger needle to remove a sample
- Surgical biopsy, which removes a sample in a minor, outpatient procedure
Fine needle aspiration and core needle biopsies usually include the following steps:
- You will lay on your side or sit on an exam table.
- A health care provider will clean the biopsy site and inject it with an anesthetic, so you won’t feel any pain during the procedure.
- Once the area is numb, the provider will insert either a fine aspiration needle or core biopsy needle into the biopsy site and remove a sample of tissue or fluid.
- You may feel a little pressure when the sample is withdrawn.
- Pressure will be applied to the biopsy site until the bleeding stops.
- Your provider will apply a sterile bandage at the biopsy site.
In a surgical biopsy, a surgeon will make a small cut in your skin to remove all or part of a breast lump. A surgical biopsy is sometimes done if the lump can’t be reached with a needle biopsy. Surgical biopsies usually include the following steps.
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We Will Look At Several Factors Including:
- Where the cancer cells originated
- How the breast cancer cells look under the microscope
- Whether the breast cancer cells react to hormones
- The genetic makeup of the cancer cells
We will then use that information to chart a treatment course that reflects your goals, personal desires, and unique nature of your particular type of breast cancer.
Her2 Status In Breast Cancer
If your cancer appears to be aggressive and fast-growing, you might have higher levels of a protein called human epidermal growth factor receptor 2, or HER2 for short. Some genes, like HER2, and the proteins they make, do more than play a role in the development of breast cancer. They can also influence how your breast cancer behaves as well as how it may respond to a specific cancer treatment.
Normally, HER2 receptors help control how a healthy breast cell grows, divides, and repairs itself. However, if the HER2 gene doesnt work correctly and produces too many copies of itself, it leads to uncontrolled growth of breast cancer cells.
What does it mean to be HER2- negative or positive?
If your breast cancer is HER2-negative, it means that you do not have an excess of the HER2 gene. Tumors such as these will not respond to therapies that specifically target HER2 receptors.
If your breast cancer is HER2-positive, then you have too much HER2 protein or extra copies of the HER2 gene. These breast cancers tend to be fast-growing. HER2-positive breast cancer treatment typically includes targeted therapy drugs that slow the growth and kill these cancer cells. HER2-positive breast cancers account for about 25% of all breast cancer cases.
Knowing your HER2 status will help your RMCC cancer care team create the best treatment plan for you.
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Errs Agonists And Antagonists
Although no endogenous ligands have been identified for these receptors several natural phytoestrogens have been identified as potential ligands of these receptors with agonistic activities, by structure-based virtual screening and biological functional assays . Phytoestrogens are produced by plants, and represent the major natural exogenous sources of estrogenic compounds. DY131 is another ERR agonist, specific to ERR and ERR that was shown to enhance growth inhibition, which was caused by overexpression of these nuclear receptors . Inhibition of ERR with the inverse agonist XCT790 reduces cell proliferation of various cancer cell lines, including prostate and breast cancer cells .
On the other hand, diethylstilbestrol and the tamoxifen metabolite, 4-hydroxytamoxifen, have been shown to interact with ERR and ERR and act as antagonists . SR16388, a novel steroidal antiestrogen, inhibits the interaction between its coactivator peroxisome proliferator-activated receptor coactivator-1 to inhibit ERR activity .