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What Is Er Pr Positive Breast Cancer

Tests On Your Breast Cancer Cells

Treatment Options for ER/PR Positive Breast Cancers

After a biopsy or surgery to remove breast tissue, a sample of cells is sent to the laboratory. A;doctor called a pathologist does various tests on the cells. This can diagnose cancer and also show which type of cancer it is.;

Some tests can also show;how well particular treatments might work, such as hormone therapies or targeted cancer drugs.

Solving A Breast Cancer Mystery Why Do Double

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Dr Jason Carroll working in his lab

When a doctor suspects a woman might have breast cancer, one of the first things they do is take a small sample of cells from her breast, , for tests.

The cells in this tiny tissue sample carry answers to crucial questions about what happens next. First and foremost is it cancer or not? If it is cancer, has it started spreading? And how aggressive it is likely to be?

The levels of different molecules within these cells also yield information about cancers nature and in breast cancer, one of the most crucial for helping guide treatment is the oestrogen receptor .

Women with high levels of this molecule in their cancer cells benefit from hormone therapy drugs that either lower their oestrogen levels, or prevent cancer cells responding to the hormone. About 7 out of ten women have ER-positive breast cancer.

But theres a second molecule the progesterone receptor levels of which inside breast cancer cells also seem to be important. Doctors have known for a long time that women with high levels of both the oestrogen and progesterone receptors have the best chance of surviving they respond better to treatment, and their cancer is less likely to spread.

But these double-positive women are given the same hormone therapy as those who have no progesterone receptor in their breast cancer, so doctors dont always routinely test for this second molecule any more.

American Society Of Clinical Oncology Guidelines

In 2014, the American Society of Clinical Oncology published a Clinical Practice Guideline to address systemic therapy for patients with advanced HER2+ breast cancer.43 These guidelines are formulated by a multidisciplinary group of experts using a review of phase III randomized controlled trials and their clinical experience. The guidelines that are relevant to first-line treatment are reviewed here.

HER2-targeted therapy combinations should be recommended for first-line treatment, except for highly selected patients with ER- and/or PR-positive breast cancers who may receive endocrine therapy alone . This recommendation is based on trials, including the pivotal trial by Slamon and colleagues,2 which showed that HER2-targeted therapy in combination with chemotherapy in the first-line setting led to improvements in response rates, PFS, TTP, and OS compared with chemotherapy alone. In the endocrine therapy trials,39,40 the addition of HER2-targeted therapy improved RR and PFS but not OS.

The combination of trastuzumab, pertuzumab, and taxane should be recommended for first-line treatment, unless the patient has a contraindication to taxane treatment . This recommendation is based on the CLEOPATRA trial,18,19 which showed an improvement in PFS and OS. The panel felt that paclitaxel could be used in place of docetaxel. The data for other chemotherapy agents were more limited, and the panel felt that these should generally be avoided until more data are available.

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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.

Defining The Immune Landscape

Breast Cancer: Its Diagnostic Tests And Interpretation of ...

Considering the dynamic nature of the immune system, we conducted the graph learning-based dimensionality reduction analysis using reduceDimension function to illustrate the intrinsic structure and distribution of individual patients . The discriminative dimensionality reduction with trees was used as dimension reduction method, and the maximum number of components was set to 2. After dimension reduction and ordering, the immune landscape was finally inferred by plot cell trajectory function.

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About Hormone Receptors And Breast Cancer

Hormone receptors are proteins found in and on the surface of breast cancer cells that pick up signals and tell the cells to grow.

A cancer is estrogen-receptor-positive if it has receptors for the hormone estrogen. A cancer is progesterone-receptor-positive if it has receptors for the hormone progesterone.

Breast cancers can be:

  • estrogen-receptor-positive and progesterone-receptor-negative
  • estrogen-receptor-negative and progesterone-receptor-positive

A breast cancer with either estrogen or progesterone receptors or both types of receptors is considered hormone-receptor-positive. Hormone-receptor-positive breast cancer treatment plans have certain standards of care, and these standards of care do not change if the breast cancer is positive for only one hormone receptor.

Because of the way the genes that make the estrogen receptor proteins and progesterone receptor proteins work, a number of doctors believe that it is biologically impossible for a breast cancer to be estrogen-receptor-negative and progesterone-receptor-positive.

So there has been controversy over whether estrogen-receptor-negative, progesterone-receptor-positive breast cancer is a true subtype or a misclassification made when less research had been done.

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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How Her2 Affects Staging

Your HER2 status helps determine the pathology of your specific breast cancer. Your HER2 status can also help determine how aggressive the cancer is. Your doctor will use this information to evaluate your treatment options.

As of 2018, the breast cancer staging system that the American Joint Committee on Cancer uses now incorporates HER2 status.

Staging is complex and must take various other factors into account, such as:

  • the size of the tumors
  • the cancers hormone status
  • whether the cancer has spread to nearby lymph nodes
  • whether the cancer has spread beyond the breast
  • whether the cancer cells look abnormal

For example, these two cancers are both classified as stage 1B:

HER2-negative

Mexclusion Of Study Subjects Who Failed To Take Drug Long Enough To Have The Expected Efficacythe Krainick

ER positive, PR positive, HER2 negative in Breast Cancer Treatment – Dr. Nanda Rajaneesh

In study of breast cancer with letrozole, Krainick-Strobel et al. used a modified ITT analysis and PP analysis. The modified ITT analysis excluded both untreated patients and those who took study medication for less than 4 months, which was the minimum treatment duration for clinically sound assessment of tumor shrinkage. The authors stated that a valid assessment of letrozole efficacy, in terms of tumor shrinkage, required at least 4 months of treatment. The PP analysis excluded all patients with major protocol violations, these being defined as: an interval of more than 30 days between the last dose of letrozole and breast surgery; the patients refusal to undergo surgery; deviation from clinically relevant selection criteria; and any treatment with prohibited medication.

The Krainick-Strobel study is distinguished in that the subjects evaluated for efficacy were defined separately to the subjects evaluated for safety. In other words, all subjects receiving study drugs were evaluated for safety , whereas subjects evaluated for efficacy were 29 subjects and 25 subjects .

Rong Liu, … Ceshi Chen, in, 2013

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Immune Subtypes And Functional Gene Programmes

Fig. 1

Immune subtypes and gene programmes defining ER+/PR/HER2 breast cancer. A Unsupervised clustering analysis of microarray data identified five immune subtypes. B Heatmap of gene programmes significantly enriched in ER+/PR/HER2 breast cancer. Scores for gene programmes were defined as the average expression level of all genes in a particular module. In the heatmap, colors represent mean GP scores of each cluster and black dots denote modules showing highest significance for an individual subtype. C, D KaplanMeier analysis of patient survival stratified by cluster: C OS; D BCSS

How Are Breast Tumors Tested For Her2

Women newly diagnosed with invasive breast cancers should be tested for HER2.;

A biopsy or surgery sample of the cancer is usually tested with either immunohistochemical stains or Fluorescent in situ hybridization .

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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How Long Will It Take For Results

Hormone receptor status testing is not available in every laboratory. It requires experience and special training to perform and interpret. A healthcare practitioner will often send a sample to a reference laboratory and it may take several days to weeks before the results are available. It is recommended that testing be done by a lab that follows the American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations to avoid inaccurate results.

Treatment For Er Positive Breast Cancer

Er pos and pr neg breast cancer

If your breast cancer is ER positive, you may be offered hormone therapy.;;

A number of hormone therapies work in different ways to block the effect of oestrogen or reduce the amount of oestrogen in the body.;

It may be given to:

  • Reduce the risk of breast cancer coming back after surgery
  • Reduce the size of the cancer or slow down its growth
  • Treat breast cancer that has come back or spread

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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.

Comparison Of Immunogenomic Indicators And Enriched Oncogenic Pathways Among Immune Subtypes

The breast tumor-specific potential neoantigens predicted by NetMHCpan 4.0 were available from TSNAdb , by which the mutation alternation file was filtered to compute the neoantigen load in each patient . To assess the activity of oncogenic pathways, first we constructed a compendium containing 335 genes by referring to a published article . Subsequently, we applied single sample gene set enrichment analysis on these genes to calculate enrichment scores for each pathway in each sample .

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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
  • talazoparib

Medications that may be used to treat HER2-negative breast cancers that are hormone-positive include:

  • abemaciclib
  • palbociclib
  • ribociclib

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:

Hormone Therapies Slow Or Stop Cancers Growth By Changing The Hormonal Milieu

Adjuvant therapy for early stage ER-positive, HER2-negative invasive breast cancer

Tamoxifen is an oral treatment. It is a selective estrogen receptor modulator , meaning it blocks estrogen from getting into breast cells. But although tamoxifen is anti-estrogenic in the breast, it is estrogenic in others parts of the body, such as the uterus and the bones. This is good for the bones, but not good for the uterus, and this is the reason why tamoxifen slightly increases a womans risk of developing uterine cancer

The aromatase inhibitors reduce estrogen by blocking an enzyme called aromatase and keeping it from converting androgens into estrogen. Both premenopausal and postmenopausal women can use tamoxifen as hormonal therapy. But for a woman to take an aromatase inhibitor, she must be ;postmenopausal. Thats because postmenopausal women get most of their estrogen from the conversion of androgens into estrogen by the aromatase enzyme, while premenopausal women get most of their estrogen directly from their ovaries. There are drugs that a premenopausal woman can take to put her into menopause that are used as breast cancer treatments. These include goserelin and leuprolide .

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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 do this in a few ways:

  • Some hormone therapies, such as;tamoxifen, attach to the receptor in the cancer cell and block estrogen from attaching to the 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.

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-.

Figure 1

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

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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 Is A Hormone Receptor

Er Pr Positive

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.

According to BreastCancer.org, about 2 out of 3 people with breast cancer have some form of hormone receptors present. This makes them candidates for hormone therapy.

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