Tyrosine Kinase Receptor Inhibitor
Given that the activated MAPK and PI3K/AKT signaling and crosstalk between ER and growth factor pathways are the potential mechanisms of ER downregulation, blocking the growth factor pathway to treat ERlow breast cancer deserves investigation. An ongoing clinical trial is underway to assess the effect of the addition of afatinib, a highly selective, irreversible inhibitor of HER2 and EGFR , to the conventional endocrine therapy in patients with ERlow positive by Hscore measurement.
Why Does Your Estrogen Level Matter
Estrogen is a hormone. Although present in the body in small amounts, hormones have big roles in maintaining your health.
Estrogen is commonly associated with the female body. Men also produce estrogen, but women produce it in higher levels.
The hormone estrogen:
- is responsible for the sexual development of girls when they reach puberty
- controls the growth of the uterine lining during the menstrual cycle and at the beginning of a pregnancy
- causes breast changes in teenagers and women who are pregnant
- is involved in bone and cholesterol metabolism
- regulates food intake, body weight, glucose metabolism, and insulin sensitivity
Girls who havent reached puberty and women approaching menopause are most likely to experience low estrogen. Still, women of all ages can develop low estrogen.
Common symptoms of low estrogen include:
What Do The Hormone Receptor Test Results Mean
Test results will give you your hormone receptor status. It will say a tumor is hormone receptor-positive if at least 1% of the cells tested have estrogen and/or progesterone receptors. Otherwise, the test will say the tumor is hormone receptor-negative.
Hormone receptor-positive breast cancer cells have either estrogen or progesterone receptors or both. These breast cancers can be treated with hormone therapy drugs that lower estrogen levels or block estrogen receptors. Hormone receptor-positive cancers tend to grow more slowly than those that are hormone receptor-negative. Women with hormone receptor-positive cancers tend to have a better outlook in the short-term, but these cancers can sometimes come back many years after treatment.
Hormone receptor-negative breast cancers have no estrogen or progesterone receptors. Treatment with hormone therapy drugs is not helpful for these cancers. These cancers tend to grow faster than hormone receptor-positive cancers. If they come back after treatment, its often in the first few years. Hormone receptor-negative cancers are more common in women who have not yet gone through menopause.
Triple-positive cancers are ER-positive, PR-positive, and HER2-positive. These cancers can be treated with hormone drugs as well as drugs that target HER2.
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Novel Therapies And Ongoing Clinical Trials
In the past few years, research on the treatment strategies for ERpositive breast cancer has flourished, and the latest development mainly focused on precision medicinebased therapy. Currently, the benefit of novel therapies either alone or in combination with standard endocrine therapy for patients with ERlow positive breast cancer was still under investigation in several clinical trials, some of which have achieved favorable results . We believe these trials will pave the way for the future treatment options for ERlow positive breast cancer.
How Can I Increase My Estrogen Naturally
Foods and supplements that contain ingredients similar to estrogen may help boost your levels. Speak to your provider before starting any regimen to increase your estrogen.
Foods that contain phytoestrogens
Phytoestrogens are plant-based estrogens. Some studies suggest that eating foods that contain phytoestrogens helps with menopause symptoms like hot flashes. Some phytoestrogens may help promote heart health, bone health and skin elasticity. More research is needed to know for sure.
Foods that contain phytoestrogens include:
Supplements that contain phytoestrogens
The FDA doesnt regulate the safety and effectiveness of supplements, so its important to check with your provider before taking supplements. Some supplements contain phytoestrogens similar to the ones found in foods and may help manage symptoms associated with low estrogen:
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Anxiety And Mood Changes
Exercise, again, will help to stabilize your mood changes and reduce anxiety. If you have difficulty doing 20 to 30 minutes of aerobic exercise, three times a week, then begin with what you are comfortable with and try to increase your exercise program when you are ready.
Invoking the relaxation response by using deep abdominal breathing will also help you to relax, reduce anxiety and stabilize mood changes.
Talking with a professional also is recommended.
Intrinsic Subtype Of Erlow Positive Breast Cancer
Molecular classification based on gene expression profiling has confirmed the division of breast cancers into at least four disease subtypes: luminalA, luminalB, HER2enriched, and basallike. ERlow positive breast cancer is also a heterogeneous disease and could be further classified . In a study aiming to determine the intrinsic subtype of ERlow positive tumors, 62% and 27% of them were classified as basallike and HER2enriched, respectively, which were both considered ERnegative subtypes . Similar results were also found in another study, in which the PAM50 classifier was used to assess the molecular class by ER status. As a result, approximately 50% of the ERlow tumors were found to be basallike, 30% HER2enriched, and only 8% luminalB subtype. In that study, the average ER gene signature scores of ERnegative tumors and ER 1%9% tumors were similar, and both were significantly lower than that of ER 10% tumors .
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Can Other Drugs Interfere With Hormone Therapy
Certain drugs, including several commonly prescribed antidepressants , inhibit an enzyme called CYP2D6. This enzyme plays a critical role in the body’s use of tamoxifen because CYP2D6 metabolizes, or breaks down, tamoxifen into molecules, or metabolites, that are much more active than tamoxifen itself.
The possibility that SSRIs might, by inhibiting CYP2D6, slow the metabolism of tamoxifen and reduce its effectiveness is a concern given that as many as one-fourth of breast cancer patients experience clinical depression and may be treated with SSRIs. In addition, SSRIs are sometimes used to treat hot flashes caused by hormone therapy.
Many experts suggest that patients who are taking antidepressants along with tamoxifen should discuss treatment options with their doctors, such as switching from an SSRI that is a potent inhibitor of CYP2D6, such as paroxetine hydrochloride , to one that is a weaker inhibitor, such as sertraline or citalopram , or to an antidepressant that does not inhibit CYP2D6, such as venlafaxine . Or doctors may suggest that their postmenopausal patients take an aromatase inhibitor instead of tamoxifen.
Other medications that inhibit CYP2D6 include the following:
- quinidine, which is used to treat abnormal heart rhythms
Menopause And Breast Cancer
Breast cancer treatment often causes women to enter menopause prematurely. The change in hormone levels and estrogen depletion caused by stopping hormone replacement therapy or undergoing chemotherapy or hormonal therapy can trigger side effects commonly associated with menopause.
Although each woman reacts to therapy individually, certain side effects are common. We hope this information will provide you with useful tips to help you manage any side effects that you may be experiencing.
Before implementing these management strategies, please discuss your specific symptoms with your physician or nurse and ask any questions you may have. If you are seeing a complementary or alternative medicine practitioner, please let us know what you are using so we can incorporate the information into your care plan.
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How Is Low Estrogen Diagnosed
Diagnosis and treatment of low estrogen can help prevent many health issues.
If youre experiencing symptoms of low estrogen, talk with your doctor. They can assess your symptoms and make a diagnosis if needed. Early diagnosis may help prevent further complications.
During your appointment, your doctor will discuss your family health history and assess your symptoms. Theyll also perform a physical exam. Blood tests will likely be needed to measure your hormone levels.
Your follicle stimulating hormone levels may also be tested to determine whether your estrogen is low if youre experiencing:
- frequently missed periods
Does Estrogen Cause Cancer
Estrogen plays a role in causing certain cancers.
Cells in your body have hormone receptors. The hormone receptors are a type of protein. Estrogen in your bloodstream can attach to the receptors. This hormone-receptor process is part of typical body function. In healthy cells, estrogen aids normal cell function and growth.
Today, experts know that several different factors play a role in turning healthy cells cancerous. When these factors are present, estrogen can act as a spark. The hormone causes cancer cells to multiply and spread.
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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.
Clinical Suggestions For Erlow Breast Cancer
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Can Cancer Symptoms Be Mistaken For Menopause
Eleonora Teplinsky, MD, is the head of breast medical oncology at Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, and is a clinical assistant professor of medicine at the Icahn School of Medicine at Mount Sinai. She specializes in the treatment of breast and gynecologic cancers. Her research interests focus on the role of exercise and nutrition in cancer and survivorship. She is also a member of the Cancer.Net Editorial Board. You can follow Dr. Teplinsky on . View Dr. Teplinskys disclosures.
People approaching or going through menopause may be concerned that the symptoms theyre experiencing are related to menopause or another medical condition, such as cancer. But can the symptoms of menopause mimic those of certain types of cancer? Or, can menopause and its treatment increase a persons risk of cancer?
Heres what to know about how the symptoms of menopause can be similar to those of cancer and whether menopause impacts cancer risk.
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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Efficacy Of Adjuvant Hormonal Treatment
Adjuvant endocrine therapy is recommended for nearly all women with a breast tumor that expresses ERs or progesterone receptors. The first critical overview of data unequivocally demonstrated that tamoxifen was associated with a highly significant improvement in relapse-free and overall survival . Its efficacy in the treatment and prevention of ER-positive breast cancer was indisputably established 8 years later in all age groups that were studied . Accordingly, 5 years of tamoxifen is the standard adjuvant treatment for patients with hormone receptor-positive early breast cancer irrespective of age, menopausal status or tumor stage .
To date, results in the adjuvant setting, regarding aromatase inhibitors, are available only for anastrozole, which was tested in the worldâs largest individual cancer trial: the Anastrozole, Tamoxifen Alone or in Combination trial. Anastrozole achieved significantly longer disease-free survival than tamoxifen as a first-line adjuvant therapy at a median follow-up of 33 months . The efficacy re-analysis at a median follow-up of 47 months confirmed the continued disease-free survival benefit in the anastrozole-treated group.
The has confirmed that in women , overall survival and recurrence-free survival significantly improved after ovarian ablation. Combination chemotherapy has also been found to substantially improve the long-term relapse-free and overall survival of both premenopausal and postmenopausal women up to the age of 70 years .
What Is Unique About The Young Mammary Gland That Makes It So Susceptible To Cancer Induction And Protection
The fact that two crucial reproductive events, menarche and young age at parity, have the greatest effect on lifetime breast cancer risk suggests that the young mammary gland represents a crucial window in tumorigenic susceptibility. Why this is the case is less clear. Based on the epidemiological evidence for this, a few hypotheses have been generated, but again few have been tested experimentally, and this work is largely restricted to rodent models.
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Outcomes From Chrt Versus Placebo
This WHI study reported six times. The first five reports between 2002 and 2009 were based on a randomized controlled trial. The fifth report incorporated a prospective observational cohort with follow-up for a further 8 years .
The second report focused more on women who developed breast cancer after an average of 5.6 years in the randomized controlled trial. Shapiro et al highlighted that there was a degree of contamination with 331 women in the concurrent estrogen replacement trial who still had a uterus, who were unblinded and added to the combined estrogen plus progesterone group versus placebo trial. Nevertheless, for all breast cancers, the hazard ratio was 1.24 : 1.02 – 1.50) when 8,507 women aged 50 – 79 years who received cHRT were compared to 8,102 similar women who received placebo.
Based on the WHI randomized controlled trial only and not the sixth report , which was a combination of randomized controlled trial and follow-on observational study, the WHI studies of cHRT versus placebo show a causal link between cHRT and incidence of breast cancer. The long-term results confirm this causality .
Biological Basis For The Carcinogenic Effects Of Estrogen
Richard Santen, MD: Compelling evidence that endogenous estrogen and breast cancer are associated comes from studies of breast cancer in women undergoing bilateral oophorectomy before age 35 years from 1920 to 1940. These women were followed for 20 to 40 years after surgery to determine whether they would develop breast cancer. The control group consisted of age-matched women who had undergone unilateral oophorectomy.
Breast cancer developed 75% less frequently in women without functioning ovaries. This protective effect gradually increased over a follow-up period of more than 25 years .
Prospective studies conducted by Toniolo et al provide additional evidence of this association. They found that women who develop breast cancer over a 5- to 10-year period have levels of estradiol approximately 20% higher than those who do not. As shown in Figure 3, these data have been confirmed by some more recent investigations but not by all such studies.
There are multiple sources of endogenous estrogen. The premenopausal ovary secretes estradiol, peripheral adipose tissues can aromatize androgen substrates to estrogens, and breast tissue itself contains aromatase and can synthesize estrogen in situ. Nearly 100% of endogenous estrogen originates from the ovary during the mid-cycle estrogen surge, whereas extraglandular production provides 50% at the time of menses. In postmenopausal women, the ovary produces no estradiol, whereas extraglandular sites predominate as sources.
Discussion
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Normal Benign Breast Control Cases
Normal breast epithelium was present in 10 core samples from YTMA-55. The number of interpretable individual ductal profiles within each clinical case ranged from 2 to 10 with positive object counts ranging from 2 to 51, demonstrating a dynamic range of mean nuclear DAB from 38.3 to 212 . As expected, there was no correlation between the mean nuclear DAB OD and positive object count . Mean nuclear DAB of the low ER cases were significantly lower than that of the normal ER control cases and the YTMA-55 control cases based on linear mixed effects model .
Fig. 2: Mean Nuclear OD in Low ER and control groups.
The mean nuclear OD values were log transformed. Cases of Low ER are compared to normal epithelium in the matched clinical full section control cases and in core tissue on YTMA-55. The lower and upper bars represent the minimum and maximum, respectively the lower and upper edges of the box represent the 25th and 75th percentiles, respectively the line in the middle of the box represents the median the gray dots represent log transformed mean nuclear OD values.