Breast Cancer And Hormone Replacement Therapy
Menopause can trigger unpleasant side effects such as hot flushes and vaginal dryness. Hormone replacement therapy eases the symptoms by boosting sex hormone levels. It also reduces the risk of osteoporosis and heart disease.;
Since some breast cancers depend on oestrogen, women taking HRT for a long time have a 0.3-fold increased risk. Women who undergo HRT for shorter periods have the same risk of breast cancer as women who have not used HRT. The health benefits of HRT in women in early post-menopause may outweigh the risks in many cases.
How Does Hormone Therapy Work
About 2 out of 3 breast cancers are hormone receptor-positive. Their cells have receptors for the hormones estrogen and/or progesterone which help the cancer cells grow and spread.
There are several types of hormone therapy for breast cancer. Most types of hormone therapy either lower estrogen levels or stop estrogen from acting on breast cancer cells.
What Is Hormone Therapy
Hormone therapy slows or stops the growth of hormone-sensitive tumors by blocking the bodys ability to produce hormones or by interfering with effects of hormones on breast cancer cells. Tumors that are hormone insensitive do not have hormone receptors;and do not respond to hormone therapy.
Hormone therapy for breast cancer should not be confused with menopausal hormone therapy treatment with estrogen alone or in combination with progesterone to help relieve symptoms of menopause. These two types of therapy produce opposite effects: hormone therapy for breast cancer blocks the growth of HR-positive breast cancer, whereas MHT can stimulate the growth of HR-positive breast cancer. For this reason, when a woman taking MHT is diagnosed with HR-positive breast cancer she is usually asked to stop that therapy.
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Signs Of Estrogen Dominance
Estrogen can be metabolized in your body in different ways. Some pathways lead to estrogen metabolites that can compromise your health. This can be a particular problem if your liver is not functioning well. Then your liver doesnt process estrogen metabolites and help remove them from your body, and you end up with more estrogen circulating, causing havoc and estrogen excess.
ED can mean one of two things: you either have too much estradiol in relation to progesterone, or an imbalance in your estrogen metabolites .
This can lead to the following symptoms:
- Worsening PMS
- Lumpy, painful or swollen breasts
- Weight gain, particularly around the hips
How Is The Test Used
Hormone receptor testing of breast tumor tissue is used to determine if estrogen receptors and/or progesterone receptors are present and whether the tumor tissues depend on estrogen and/or progesterone to grow. Knowing if a tumor grows under the influence of hormones indicates whether removal of ones ovaries, which produce the hormones, or blocking the hormones with drugs can inhibit tumor growth to prolong survival. Studies have demonstrated a benefit from such hormone therapy for patients with ER-positive tumors.
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Role Of Estrogen Receptor Signaling In Breast Cancer Metastasis
Ratna K. Vadlamudi
1Department of Obstetrics and Gynecology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
Metastatic breast cancer is a life-threatening stage of cancer and is the leading cause of death in advanced breast cancer patients. Estrogen signaling and the estrogen receptor are implicated in breast cancer progression, and the majority of the human breast cancers start out as estrogen dependent. Accumulating evidence suggests that ER signaling is complex, involving coregulatory proteins and extranuclear actions. ER-coregualtory proteins are tightly regulated under normal conditions with miss expression primarily reported in cancer. Deregulation of ER coregualtors or ER extranuclear signaling has potential to promote metastasis in ER-positive breast cancer cells. This review summarizes the emerging role of ER signaling in promoting metastasis of breast cancer cells, discusses the molecular mechanisms by which ER signaling contributes to metastasis, and explores possible therapeutic targets to block ER-driven metastasis.
2. ER Signaling Mechanisms
3. ER Genomic Actions and Metastasis
4. ER Extranuclear Actions and Metastasis
. Green; EDC; Blue, DAPI.
5. ER Regulation of Metastasis
6. ER Regulation of Cell Migration and Metastasis
7. Estrogen Regulation of EMT
8. Tumor Microenvironment Regulation of ER Signaling
Estrogen And Progesterone Receptor Testing For Breast Cancer
To help doctors give their patients the best possible care, the American Society of Clinical Oncology and the College of American Pathologists developed evidence-based guidelines to improve the accuracy of testing for estrogen and progesterone receptors for breast cancer. This guide for patients is based on ASCO’s and CAP’s 2020 updated recommendations.
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What Are The Treatment Options For Er
In addition to surgery, treatments for ER-positive breast cancers include:
- Targeted therapies
Burstein says there has been a sea change in the use of chemotherapy for early-stage ER-positive breast cancer, thanks to tests of the genomic characteristics of a tumor and which allow the majority of women to avoid chemotherapy.
For premenopausal women with early, low-risk breast cancers, there is growing recognition that ovarian suppression rather than chemotherapy is an important treatment to reduce the chances of recurrence. Chemotherapy is indicated, however, for women with larger ER-positive tumors with higher-risk genomic features.
Endocrine therapy for five to 10 years, to prevent metastatic disease, recurrence, and tumors in the opposite breast, is recommended for almost all patients with ER-positive breast cancer. Previously, tamoxifen was the standard endocrine therapy, but in recent years, there have been more options, such as aromatase inhibitors, which are more effective than tamoxifen, especially in higher-risk cancers. Endocrine therapy is also standard treatment for metastatic disease.
All the endocrine therapies carry some risks and have side effects. Bursteins review notes that better understanding of these side effects and how to manage them can help providers individualize therapy for patients.
Less Common Types Of Hormone Therapy
Some other types of hormone therapy that were used more often in the past, but are rarely given now include:
- Megestrol acetate , a progesterone-like drug
- High doses of estrogen
These might be options if other forms of hormone therapy are no longer working, but they can often cause side effects.
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What Are The Symptoms Of Breast Cancer
The most common symptom of most breast cancers is a lump in the breast. A painless, hard mass with irregular edges is most likely cancer, but breast cancers can also have a lump that is soft and tender to the touch. Other possible symptoms in the first three stages of breast cancer include:
- Change in the size and shape of the breast
- Asymmetry in the breast compared to the other
- Skin dimpling or other abnormal changes in the breastâs skin
Breast Cancer Hormone Receptor Status
Breast cancer cells taken out during a biopsy or surgery will be tested to see if they have certain proteins that are estrogen or progesterone receptors. When the hormones estrogen and progesterone attach to these receptors, they fuel the cancer growth. Cancers are called hormone receptor-positive or hormone receptor-negative based on whether or not they have these receptors . Knowing the hormone receptor status is important in deciding treatment options. ;Ask your doctor about your hormone receptor status and what it means for you.
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How Her2 Status Affects Treatment
For more than 30 years, researchers have been studying HER2-positive breast cancer and ways to treat it.
Targeted therapies have now changed the outlook of stage 1, 2, and 3 breast cancers from poor to good.
While targeted therapies are part of the standard treatment for HER2-positive breast cancer, theyre only used occasionally in HER2-negative breast cancer.
Another difference between HER2-positive treatments and HER2-negative treatments is that HER2-negative treatments are often oral medications. HER2-positive treatments are usually administered intravenously or by injection.
For HER2-positive or HER2-negative breast cancers that are estrogen-positive or progesterone-positive, treatment with hormonal therapy may also be recommended.
Medications that may be used to treat HER2-negative breast cancers that are hormone-negative include:
- sacituzumab govitecan , an IV treatment
Medications that may be used to treat HER2-negative breast cancers that are hormone-positive include:
Some of these medications are taken on their own, while others must be administered with other medications. Factors that affect your treatment regimen include whether:
- youve gone through menopause
- youve already received hormone therapy or chemotherapy
- you have certain gene mutations
Trastuzumab is a biologic therapy thats administered intravenously.
Other treatments for HER2-positive breast cancer include:
Current Treatment Options For Er+ Breast Cancer
In general, surgery is the only way to cure most malignancies originated from solid organs. After diagnosis, patients with breast cancer in early stage should undertake surgery with or without radiotherapy, irrespective to the subtypes of breast cancer. There are two major surgical approaches for breast cancersmastectomy and lumpectomy . The appealing advantage of lumpectomy enables patients to preserve their breast without compromising survival outcome. With the addition of radiotherapy following lumpectomy, survival outcomes have been reported to be equivalent to those after mastectomy as primary disease control in breast cancers with early stage .
Besides primary tumor resection, axillary lymph node dissection or sentinel lymph node biopsy and resection is also essentially performed on breast cancer patients to determine possible spread of cancer cells to lymph nodes from the original breast tumor. If the SLN examination reveals no evidence of malignant cell involvement, any other area of the body without cancer cell metastases would be highly postulated. Notably, the effectiveness of the SLN procedure to determine the presence of lymph node metastases is demonstrated to be identical to that of ALN dissection in various clinical studies.
2.2.2 Selective estrogen receptor modulators
2.2.3 Aromatase inhibitors
Clinical benefits of using aromatase inhibitors in ER+ breast cancers.
DFS, disease-free survival; HT, hormone therapy; HR, hazard ratio.
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Survival Analysis Of Single Hormone Receptor
Approximately 97% of patients with ER + PR- tumors and 88% of patients with ER-PR+ tumors received endocrine therapy. More patients with ER + PR- and ER-PR+ tumors received chemotherapy than the group with ER + PR+ tumors , but less than the group with ER-PR- tumors . Approximately 72% of patients with ER + PR- tumors received both endocrine therapy and chemotherapy, and 24.9% of patients received only endocrine therapy. In ER-PR+ tumors, 80% of patients received both chemotherapy and endocrine therapy, 8.2% of patients received only endocrine therapy and 9.4% of patients received only chemotherapy.
With univariate analysis by Kaplan-Meier method, the survival graph of ER + PR- tumors was located between that of ER + PR+ tumors and ER-PR- tumors. The 5-year and 10-year DFS of ER + PR- tumors was 91.4% and 79.6%, respectively, and the 5-year and 10-year OS was 95.9% and 93.9%, respectively. Patients with ER-PR+ tumors had worse DFS and OS than those with ER + PR-.
Among 1,376 patients with HER2 overexpression, there was no significant difference in DFS between four subgroups , and patients with ER-PR-HER+ tumors had the worst OS . However, the 790 patients who received trastuzumab therapy had similar OS , as did the 586 patients who did not receive trastuzumab therapy .
Figure 2Figure 3Table 2 Multivariate analysis of disease-free survival and overall survival in 1.376 women with HER2-positive breast cancer
When Is Hormone Therapy Used
Hormone therapy is often used after surgery to help reduce the risk of the cancer coming back. Sometimes it is started before surgery . It is usually taken for at least 5 to 10 years.
Hormone therapy can also be used to treat cancer that has come back after treatment or that has spread to other parts of the body.
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Minimize Exposure To Heavy Metals
Heavy metals including copper, cobalt, arsenic, cadmium, mercury and lead have been found to stimulate estrogen receptors. Sources of arsenic include some brands of rice, seafood, well water; cadmium is high in cigarettes and can be found in some soils; mercury is mainly prevalent in larger fish and old dental amalgams; and lead contamination is a component of air pollution, paint and dyes, and ceramic glazes among other sources.
Essentially, heavy metal and toxin exposure is hard to completely avoid in our world, even with careful choices. Because of this, I advise my patients to use compounds that provide safe, gentle detoxification of heavy metals and other contaminants, on a daily or periodic basis.
Modified citrus pectin, is derived from the pith of citrus fruit and has been shown in human studies to remove harmful heavy metals and reduce toxic body burden over time. MCP is able to cross the intestinal barrier and circulate in the bloodstream, where it binds to toxins and heavy metals and helps safely excrete them, without removing essential minerals. I also recommend ingredients such alpha-lipoic acid, N-acetyl cysteine, garlic, cilantro and other herbs and nutrients that provide support for our bodys complex detoxification systems.
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 2 of 3 breast cancers have at least one of these receptors. This percentage is higher in older women than in younger women. DCIS should be checked for hormone receptors, too.
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Questions To Ask Your Doctor
To learn more about estrogen and progesterone receptor testing for breast cancer, consider asking your doctor the following questions:
What are the results of the ER and PR tests on my tumor sample? What do they mean?
Does this laboratory meet the standard guidelines like those from ASCO and the CAP?
Has a board-certified pathologist diagnosed my cancer?
Do you know if this is an experienced lab and if my tissue was quickly given to the pathologist after my biopsy or surgery, as recommended by guidelines?
Can I obtain a copy of my pathology report ?
Is my ER and PR status indicated on the pathology report? Was the ASCO-CAP guideline recommendation used to define the status?
Based on these test results, what treatments do you recommend and why?
- What are the possible side effects of these treatments?
What Are Estrogen And Progesterone Receptors
Receptors are proteins in or on cells that can attach to certain substances in the blood. Normal breast cells and some breast cancer cells have receptors that attach to the hormones estrogen and progesterone, and depend on these hormones to grow.
Breast cancer cells may have one, both, or none of these receptors.
- ER-positive: Breast cancers that have estrogen receptors are called ER-positive cancers.
- PR-positive: Breast cancers with progesterone receptors are called PR-positive cancers.
- Hormone receptor-positive: If the cancer cell has one or both of the receptors above, the term hormone-receptive positive breast cancer may be used.
- Hormone receptor-negative: If the cancer cell has neither the estrogen nor the progesterone receptor, it’s called hormone-receptor negative .
Keeping the hormones estrogen and progesterone from attaching to the receptors can help keep the cancer from growing and spreading. There are drugs that can be used to do this.
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How Breast Cancer Forms And Multiplies
Cancer cells are triggered when a mutation in normal cells occur. This can happen due to well-known problematic lifestyle factors like living on junk food, chronic sunburn and cigarette smoking, but hormones can also play a big role. Once cancer cells are born they grow and divide to make more cancer cells, which form a tumor that may contain millions of cancer cells.
Cancers need a blood supply to provide them the oxygen, nutrients and hormones like estrogen, which help them grow and multiply. But as they get bigger they are often further away from the blood vessels so they need to set up their own supply. They do this by sending out signals that tell your body to grow new blood vessels like capillaries. This process is called angiogenesis. And it is ongoing, so once it occurs the cancer keeps getting bigger and then may start to spread to organs like your liver . Thats why scientists are working on cancer vaccines and drugs to try to halt the process of angiogenesis.
Breast cancer is often caused by cancer cells growing in the lobules, where milk is produced or the ducts, where the milk travels to the nipple. Breast cancer cells may then spread to surrounding breast tissue, then move to the lymph nodes under the arms and migrate to other parts of the body.
Oestrogen Receptor Positive Breast Cancer
Oestrogen is a hormone that plays an important role in the female reproductive system.;
Sometimes breast cancer cells contain oestrogen receptors. This is called oestrogen receptor positive or ER positive breast cancer, often shortened to ER+.
When oestrogen receptors are found in breast cancer cells, this can help the breast cancer to grow.;
All invasive breast cancers are tested for oestrogen receptors using tissue from a biopsy or after surgery. Invasive breast cancer is cancer that has the potential to spread.
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