Most Breast Cancers Are Not Genetic
Only five percent of breast cancers are related to genetics and even then, that doesnt mean that all women with the BRAC genes that make them more vulnerable, will go on to develop breast cancer.
Though you cant alter risk factors like your age or parents, simple lifestyle changes can do a great deal to protect you from developing breast cancer.
One of the least discussed but most important steps is to reduce risks caused by too much estrogen.
In my experience working with women, estrogen dominance is very common, but often women dont know the signs or even realize that ED is a concern or that it kick starts substantial health risks.
Load Up On Fruits And Vegetables
The fiber, antioxidants and other phytonutrients in fruits and vegetables have the potential to reduce cancer growth, although research results have been mixed on their role in breast cancer. In fact, data from the Women’s Healthy Eating and Living trial, a study of more than 3,000 women with a history of early-stage breast cancer, failed to show a diet rich in these foods reduced the rate of recurrence.
However, data from the Women’s Health Observational Study , a trial of nearly 94,000 postmenopausal women with a history of early-stage breast cancer, linked a higher intake of carotenoid-rich fruits and vegetables, such as leafy greens, carrots, sweet potatoes and nectarines, to a lower recurrence of ER-positive breast cancer.
In addition, a 2008 study in the Journal of Clinical Oncology of nearly 1,500 women with early-stage breast cancer found those who ate at least five daily servings of fruits and vegetables and exercised 30 minutes daily cut their risk of death in half over a 10-year period. This benefit was greatest among women with ER-positive breast cancer.
Eating a diet rich in fruits and vegetables can do more than cut cancer risk. A plant-centered, high-fiber diet can also reduce the risk of other health problems that breast cancer patients may face, such as obesity and cardiovascular disease. Consequently, women with breast cancer are encouraged to include a variety of colorful fruits and vegetables in their daily diets.
Mechanisms Of Hormone Therapy Resistance In Er+ Breast Cancer
Despite various hormone therapy agents have been developed and proven to be effective in treating ER+ early stage breast cancer, intrinsic and acquired resistance to hormone therapy are frequently observed in breast cancer patients. In the following sections, we will discuss the biology behind the induction of hormone therapy resistance in ER+ breast cancer in details.
2.3.1 Dysregulation and conformation alteration of ER
Under normal physiological conditions, the binding of estrogen to ER will trigger ER conformation changes and ER dimerization . Then, the activated ER dimers will bind onto the estrogen response elements and drive the expression of the ERE-regulated cell survival- and growth-related genes. Decreased ER expression and reduced survival dependence on the estrogen-ER signaling pathway are both known to promote hormone therapy resistance in ER+ breast cancer. For example, upregulation of the zinc-finger-homeodomain transcription factor, zinc-finger E-box binding homeobox 1 , has been shown to downregulate ER expression epigenetically through formation of a ZEB1/DNA methyltransferase 3B /histone deacetylase 1 complex on the promoter of ER and to induce tamoxifen resistance in breast cancer cells. High ZEB1 expressions also correlate with ER promoter hyper-methylation and reduced ER expression in breast cancer patients .
2.3.2 Dysregulation of cell survival-related signaling pathways and pro-/anti-apoptotic molecules
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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.
Targeting Er And Oestrogen Signalling In Breast Cancer Prevention And Treatment
For several decades following Beatsons initial published report, castration by surgical means or by irradiation was used to treat premenopausal women with recurrent or distant metastatic breast cancer. In some postmenopausal women, high doses of androgen or, paradoxically, the synthetic non-steroidal oestrogen diethylstilbestrol was effective in the treatment of advanced diseases . Identification of ER and the development of methodology to detect its expression by hormone binding assays in tumour samples enabled the clinical studies required that ER be established as a prognostic marker for response to hormone therapy, and determining the ER-status of tumour samples is now standard practice in clinical oncology .
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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.
Proteins For Targeted Cancer Drugs
Testing cancer cells for particular proteins can help to show whether targeted drug treatments might work for your breast cancer.
Targeted cancer drugs are treatments that change the way cells work and help the body to control the growth of cancer.
Some breast cancers have large amounts of a protein called HER2 receptor . They are called HER2 positive breast cancers. About 15 out of every 100 women with early breast cancer have HER2 positive cancer.
Targeted cancer drugs such as trastuzumab can work well for this type of breast cancer. These drugs attach to the HER2 protein and stop the cells growing and dividing.
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How Do Hormone Therapies Work
Hormone therapies slow or stop the growth of hormone receptor-positive tumors by preventing the cancer cells from getting the hormones they need to grow.
They work in a few ways:
- Some hormone therapies, such as tamoxifen, attach to the hormone receptor in the cancer cell and block estrogen from attaching to the hormone receptor.
- Some hormone therapies, such as aromatase inhibitors and ovarian suppression, lower the level of estrogen in the body so the cancer cells cant get the estrogen they need to grow.
When Is Hormone Therapy Used For Breast Cancer
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 years. Treatment longer than 5 years might be offered to women whose cancers have a higher chance of coming back. A test called the Breast Cancer Index might be used to help decide if a woman will benefit from more than 5 years of hormone therapy.
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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Clinicopathologic Characteristics Of The Study Population
The flowchart of selection process was shown in Supplementary Figure 1. A total of 203406 patients were included, including 133662 patients for ER+PR+HER2-, 16906 for ER+PR-HER2-, 1395 for ER-PR+HER2-, 21439 for ER-PR-HER2- and 15646 for ER+PR+HER2+, 5381 for ER+PR-HER2+, 537 for ER-PR+HER2+, and 8440 for ER-PR-HER2+. The median follow-up duration of the study population was 35 months . The clinicopathologic characteristics of each subtype were summarized in Table 1.
Table 1 Clinicopathologic characteristics of the study population .
What Does Estrogen Receptor Positive Mean
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.
Combined Oral Contraceptive Use
COC use was not associated with risk of either ER+PR+ or ER-PR- breast cancer . Women who had used COC for 10 years or longer had a slightly higher OR of ER- PR- breast cancer but a lower OR of ER+PR+ breast cancer compared with never users. ER+PR+ case patients were less likely to have had longer duration of COC use than ER- PR- case patients .
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Side Effects Of Tamoxifen And Toremifene
The most common side effects of tamoxifen and toremifene are:
- Hot flashes
- Vaginal dryness or discharge
- Changes in the menstrual cycle
When tamoxifen treatment starts, a small number of women with cancer that has spread to the bones might have a tumor flare which can cause bone pain. This usually decreases quickly, but in some rare cases a woman may also develop a high calcium level in the blood that is hard to control. If this happens, the treatment may need to be stopped for a time.
Rare, but more serious side effects are also possible:
Determining Your Breast Cancer Type
At Rocky Mountain Cancer Centers , we understand that the diagnosis of cancer can be overwhelming, not only for you, but also for your friends and relatives. Therefore, the sooner we determine your specific breast cancer type, the sooner we can get you on the path to treatment and recovery. To do this, we will perform an in-depth evaluation on the tissue sample collected from your breast biopsy, or on the tumor itself after your breast cancer surgery.
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Clinical Case Selection And Controls
A retrospective pathology report search of the Yale Pathology electronic pathology record was performed to identify invasive breast carcinomas with reported low ER expression between the years of 2011 and 2018, and interpreted using 2010 ASCO/CAP criteria. Glass slides of the original ER stained sections were retrieved from the archive for digital scanning. Pathologic and clinical features including patient age at the time of diagnosis, tumor grade, ER, PR and HER2 status were obtained from the pathologic report .
Discovery And Characterisation Of Ers
Adding to the mechanistic complexity and refinement of oestrogen signalling, a second ER gene was discovered in 1996 by Gustafsson and Kuiper and was named ER . The original ER was renamed ER. ER and ER share a 56% similarity in their ligand-binding domains, and both bind the predominant endogenous oestrogen 17-estradiol. The differences in their ligand-binding domains, however, also result in selective binding of natural and synthetic ligands and allow for selective targeting of each receptor subtype. The two receptors have nearly identical DNA binding domains and share affinity for the canonical ERE. Studies of ER-positive MCF7 breast cancer cells engineered to express ER have confirmed a substantial overlap of DNA-binding sites between the two receptors . Intriguingly, their similarities in DNA binding resulted in different gene expression profiles with only a minority of ER-regulated genes also regulated by ER . These functional differences may be due to the low conservation of their respective N-terminal AF-1 domains and their different abilities to interact with co-regulators . When co-expressed, ER and ER can function as both homodimers and heterodimers these complexes appear to have their own transcriptional activities and regulate distinct gene sets .
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Progesterone And Breast Cancer
Progesterone is another hormone that plays a role in the female reproductive system.
Sometimes breast cancer cells contain progesterone receptors. This is called progesterone receptor positive or PR positive breast cancer, often shortened to PR+.
Invasive breast cancers should also be tested for progesterone receptors.
How Are Breast Tumors Tested For Her2
Either a test called an immunohistochemistry test or fluorescence in situ hybridization test is used to find out if cancer cells have a high level of the HER2 protein.
See Testing Biopsy and Cytology Specimens for Cancer and Understanding Your Pathology Report: Breast Cancerto get more details about these tests.
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What This Means For Patients
Because the results of ER and PR testing can make a difference in a persons treatment and chance of recurrence, it’s important that these tests are accurate. This guideline was developed to help both doctors and laboratories know how to improve the accuracy of ER and PR testing for those with breast cancer. Understanding the ER/PR status of the primary tumor and any distant or recurrent tumors can help doctors make sure that patients receive the appropriate treatment and avoid side effects of a treatment that may not work. Use this guideline to talk with your doctor about the accuracy of your ER and PR test results and what that means for your treatment.
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:
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?