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Breast Cancer Hormone Positive Her2 Negative

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How Long Does It Take For Stage 1 Breast Cancer To Develop Into Stage 2

Updates on hormone receptor-positive HER2-negative breast cancer

It is not possible to determine exactly how long it will take for newly diagnosed breast cancer to progress from stage 1 to stage 2. It can happen within months if it is an aggressive high-grade tumor, or it can take longer. Itâs important to know that stage 1 breast cancer could have already been present for a while before being detected, so it may progress quickly.

Evaluation Of Immunohistochemical Staining

Positive controls and internal areas of normal breast tissues showed strong and uniform staining of the epithelial cells lining the ducts and lobules with minimal back ground reactivity for various cytokeratins, smooth muscle actin, BRCA-1, E-cadherin and GCDFP. For evaluating EGFR, CerbB2 and p53 immunostaining, a known positive external control was utilized. Two cores were evaluated from each tumor. Each core was scored individually then the mean of the two readings was calculated. If one core was uninformative, the overall score applied was that of the remaining core. Assessment of staining was based on a semiquantitative approach. A modified histochemical score was used which includes an assessment of both the intensity of staining and the percentage of stained cells. For the intensity, a score index of 0, 1, 2 and 3 corresponding to negative, weak, moderate and strong staining intensity was used and the percentage of positive cells at each intensity was estimated subjectively. A final score of 0300 is the product of both the intensity and the percentage. Staining of ER and p53 was evaluated in the nuclei of the malignant cells and scored as positive or negative. An H-score of 0 and 50 were considered as cutoff points for positive staining of ER and rest of the markers, respectively. One observer scored the staining pattern , without previous knowledge of the outcomes on two separate occasions and a good correlation between the results was found.

What Is The Prognosis For Triple Negative Breast Cancer

Triple negative breast cancer can be more aggressive and difficult to treat. Also, the cancer is more likely to spread and recur. The stage of breast cancer and the grade of the tumor will influence your prognosis. Research is being done currently to create drug therapies that are specific for triple negative breast cancer.

Interested in learning more? i3Health is hosting an upcoming webinar Metastatic Triple-Negative Breast Cancer: Applying Treatment Advances to Personalized Care. Learn more here.

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B Sequential Use Of Tamoxifen And Aromatase Inhibitors

Multiple trials evaluated the benefit of extended endocrine therapy using the strategy of switching to an AI after initial therapy with tamoxifen. For example, in the MA.17 study, 5 years of letrozole after completion of 5 years of tamoxifen was associated with improved DFS and OS compared to placebo . Likewise, the National Surgical Adjuvant Breast and Bowel Project B-33 trial demonstrated that 5 years of exemestane following 5 years of tamoxifen improved relapse free survival in patients with HR-positive, lymph node positive breast cancer . These studies coupled with others support the use of up to 10 years of endocrine therapy using sequential approaches such as 2-3 years of tamoxifen followed by an AI for 5 years or tamoxifen for 5 years followed by 5 years of an AI.

Adjuvant Chemotherapy For Hr

HER2

Recent years have witnessed an evolution in the use of adjuvant chemotherapy for HR-positive disease, with genomic assays allowing the better identification of which patients are unlikely to benefit and reducing unnecessary toxicity. Current ESMO guidelines recommend consideration of adjuvant chemotherapy for patients who have luminal A tumors and a high disease burden as well as those who have luminal B, highly proliferative tumors. In contrast, patients who have low-grade luminal A tumors with strong HR expression and low genomic risk likely derive less benefit from adjuvant chemotherapy and can be considered for endocrine therapy alone.

Regimen selection

There are considerable regional differences regarding the preferred chemotherapy regimens for HR-positive early breast cancers. In the United States and Germany, there has been a general shift away from using anthracyclines in patients who have HR-positive tumors with minimal or no nodal involvement, although practice varies between institutions. In southern Europe and the United Kingdom, anthracyclines are still commonly used, including in patients with node-negative disease.

Tolerability of adjuvant chemotherapy

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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.

Tamoxifen

  • breathing problems, including painful breathing, shortness of breath, and cough
  • loss of appetite

What Is A Hormone Receptor

Hormones are chemical messengers that circulate in the bloodstream. Hormone receptors are proteins located in and around breast cells. When the corresponding hormone binds to a receptor, it tells the cells how to grow and divide.

In the case of breast cancer, these receptors allow abnormal cells to grow out of control, which results in a tumor.

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Heterogeneity Of Hormone Receptor

Hormone receptor -positive breast cancers make up a highly heterogeneous group of malignancies. These malignancies have a risk for both early and late recurrence, with at least one-half of disease recurrences occurring > 5 years after initial diagnosis and some occurring well beyond 10 years after diagnosis. Variations in tumor grade, expression of hormone receptors and proliferative genes , and genomic alterations all contribute to the diversity of early stage, HR-positive breast cancers. These characteristics are closely tied to intrinsic subtypes and can provide valuable information regarding risk for recurrence and sensitivity to systemic therapies. However, between these 2 intrinsic subtypes lies a wide spectrum of HR-positive early breast cancers that have unique tumor biology and recurrence risk, reinforcing the importance of individualized treatment decisions .

Characteristic
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  • Abbreviations: ER, estrogen receptor HR, hormone receptor PgR, progesterone receptor.
  • a Reprinted from: Burstein H. Systemic therapy for estrogen receptor-positive, HER2-negative breast cancer. N Engl J Med. 2020 383:2557-2570, with permission from the Massachusetts Medical Society. Copyright © 2020 Massachusetts Medical Society.

Why Receptor Status Matters

Treatments for HR , HER2-Negative Metastatic Breast Cancer

Breast cancer is not a single disease, and researchers now have the ability to break down breast cancer into different subtypes based on the receptor status of the tumors. Among the variations between different types of breast cancers are the proteins found on cell surfaces, which are involved tumor growth. These proteins are related to the genetic material of cancer cells.

For example, with estrogen receptor-positive breast cancer, estrogen binds to specific receptors on breast cancer cells, stimulating proliferation. Similarly, HER2 receptors on the surface of breast cancer cells are stimulated by HER2 protein, promoting the growth and spread of breast cancer.

It’s important to note, however, that all breast cellsboth cancerous and noncanceroushave HER2 receptors on their surfaces. The difference is that HER2-positive breast cancer cells have 40 to 100 times more receptors than HER2-negative breast cancer cells or normal breast cells. In positive cases, the abundance of receptors fuels the cancer.

Breast Cancer Discussion Guide

Get our printable guide for your next healthcare provider’s appointment to help you ask the right questions.

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Overview Of Systemic Therapy Options

The treatment modalities generally employed for early stage HR-positive, HER2-negative breast cancer encompass a combination of definitive local therapy, which includes primary surgical management of the breast and axilla with or without adjuvant radiation, and adjuvant endocrine therapy with or without chemotherapy. The Early Breast Cancer Trialists Collaborative Group analysis of adjuvant chemotherapy in early stage breast cancer demonstrated that the risk of disease recurrence and death is significantly reduced with the use of adjuvant chemotherapy, irrespective of HR status. In addition, adjuvant endocrine therapy is associated with decreased risk of recurrence and death in early stage ER-positive breast cancer . Newer studies incorporating biomarkers have demonstrated that the benefit of chemotherapy is not uniform for all HR-positive breast cancers, and these are discussed in more detail below.

Hormone Receptor Status And 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 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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Tests On Your Breast Cancer Cells

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.

What Is The Life Expectancy For Each Cancer Stage

Cancers

Your outlook depends on the stage of your cancer when its discovered. Cancer is staged by number, starting with 0 and going to 4. Stage 0 is the very beginning and stage 4 is the last stage, also called the metastatic stage, because its when cancer has spread to other areas in the body.

Each number reflects different characteristics of your breast cancer. These characteristics include the size of the tumor and whether the cancer has moved into lymph nodes or distant organs, like the lungs, bones, or brain.

Research on survival statistics for people with breast cancer tends to separate participants into categories of women and men.

Survival statistics of women with the major subtypes of breast cancer such as ER-positive, HER2-positive, and triple-negative are grouped together. With treatment, most women with very early stage breast cancers of any subtype can expect a normal life span.

Survival rates are based on how many people are still alive years after they were first diagnosed. Five-year and 10-year survival are commonly reported.

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Understanding Hormone Receptor Test Results

Most labs use a special staining process that makes hormone receptors show up in a sample of breast cancer tissue. The test is called an immunohistochemical staining assay, or ImmunoHistoChemistry . Not all labs use the same method for analyzing the results of the test, and they donât report the results in exactly the same way. So you may see any of the following on your pathology report:

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    A percentage that tells you how many cells out of 100 stain positive for hormone receptors. You will see a number between 0% and 100% .

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    An Allred score between 0 and 8. This scoring system is named for the doctor who developed it. The system looks at what percentage of cells test positive for hormone receptors, along with how well the receptors show up after staining, called intensity. This information is then combined to score the sample on a scale from 0 to 8. The higher the score, the more receptors were found and the easier they were to see in the sample.

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    The word positive or negative.

Keep in mind that the breast cancer should be tested for both estrogen receptors and progesterone receptors. If your result is reported as just positive or negative, ask your doctor for a more definite percentage, rating, or other number. You also can ask about how these more precise results might influence treatment decisions for your particular situation.

Most breast cancers are hormone receptor positive:

Learn more at Hormonal Therapy.

What Are Immune Checkpoints

Immune “checkpoints” are proteins that usually help your immune system distinguish between healthy and dangerous cells. Breast cancer cells can mimic checkpoint proteins to avoid being detected by the immune system.

One IV drug, Keytruda , targets a checkpoint protein called PD-1. By blocking PD-1, Keytruda can expose and boost the immune response against breast cancer cells, which can often shrink the cancer.

Keytruda is used with chemotherapy to treat triple-negative breast cancer, which is estrogen receptor-negative, progesterone receptor-negative, and HER2-negative.

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Pam50 Cibersort And Tgf

Probe level data were normalized and converted to expression values using robust multiarray average procedure. Quality control assessment was performed in R statistical environment using affy, affyQCReport, and affyPLM Bioconductor packages.

PAM50 subtype predictor was used to assign intrinsic subtype using nearest centroid procedure. If the nearest centroid for a sample was Normal-like, second nearest centroid was selected.

Proportion of infiltrating immune cell subsets was calculated using the CIBERSORT deconvolution method . A 0.05 p-value threshold for the deconvolution result was used to filter out samples with poor fitting.

A previously published TGF- signaling response gene-expression signature was calculated and compared between luminal and non-luminal subtypes.

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What Types Of Hormone Therapy Are Used For Breast Cancer

Several strategies are used to treat hormone-sensitive breast cancer:

Blocking ovarian function: Because the ovaries are the main source of estrogen in premenopausal women, estrogen levels in these women can be reduced by eliminating or suppressing ovarian function. Blocking ovarian function is called ovarian ablation.

Ovarian ablation can be done surgically in an operation to remove the ovaries or by treatment with radiation. This type of ovarian ablation is usually permanent.

Alternatively, ovarian function can be suppressed temporarily by treatment with drugs called gonadotropin-releasing hormone agonists, which are also known as luteinizing hormone-releasing hormone agonists. By mimicking GnRH, these medicines interfere with signals that stimulate the ovaries to produce estrogen.

Estrogen and progesterone production in premenopausal women. Drawing shows that in premenopausal women, estrogen and progesterone production by the ovaries is regulated by luteinizing hormone and luteinizing hormone-releasing hormone . The hypothalamus releases LHRH, which then causes the pituitary gland to make and secrete LH and follicle-stimulating hormone . LH and FSH cause the ovaries to make estrogen and progesterone, which act on the endometrium .

Examples of ovarian suppression drugs are goserelin and leuprolide .

Blocking estrogens effects: Several types of drugs interfere with estrogens ability to stimulate the growth of breast cancer cells:

Conflict Of Interest Disclosures

We have read and understood Current Oncologys policy on disclosing conflicts of interest, and we declare the following interests: AAJ has previously provided advisory board services to Roche, Novartis, Pfizer, Eisai, and AstraZeneca, and has received educational meeting travel support from Novartis and AstraZeneca . MG and RF have no conflicts to declare. MJC has previously received meeting support from Amgen and Novartis, and has received educational meeting travel support from Novartis .

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What Is Her2 And What Does It Mean

HER2 is a protein that helps breast cancer cells grow quickly. Breast cancer cells with higher than normal levels of HER2 are called HER2-positive. These cancers tend to grow and spread faster than breast cancers that are HER2-negative, but are much more likely to respond to treatment with drugs that target the HER2 protein.

All invasive breast cancers should be tested for HER2 either on the biopsy sample or when the tumor is removed with surgery.

What Do The Test Results Mean

Cancers

The results of HER2 testing will guide you and your cancer care team in making the best treatment decisions.

It is not clear if one test is more accurate than the other, but FISH is more expensive and takes longer to get the results. Often the IHC test is done first.

  • If the IHC result is 0, the cancer is considered HER2-negative. These cancers do not respond to treatment with drugs that target HER2.
  • If the IHC result is 1+, the cancer is considered HER2-negative. These cancers do not usually respond to treatment with drugs that target HER2, but new research shows that certain HER2 drugs might help in some cases .
  • If the IHC result is 2+, the HER2 status of the tumor is not clear and is called “equivocal.” This means that the HER2 status needs to be tested with FISH to clarify the result.
  • If the IHC result is 3+, the cancer is HER2-positive. These cancers are usually treated with drugs that target HER2.

Some breast cancers that have an IHC result of 1+ or an IHC result of 2+ along with a negative FISH test might be called HER2-low cancers. These breast cancers are still being studied but appear to benefit from certain HER2-targeted drugs.

Triple-negative breast tumors dont have too much HER2 and also dont have estrogen or progesterone receptors. They are HER2-, ER-, and PR-negative. Hormone therapy and drugs that target HER2 are not helpful in treating these cancers. See Triple-negative Breast Cancer to learn more.

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