What This Means For You
If youve been diagnosed with early-stage breast cancer, your doctor may recommend treatments after surgery to reduce your risk of recurrence.
If you were diagnosed with hormone receptor-positive, early-stage breast cancer, its likely that your doctor will recommend you take some type of hormonal therapy medicine either tamoxifen or an aromatase inhibitor depending on your menopausal status for five to 10 years after surgery.
Chemotherapy after surgery is usually completed in three to six months. If youre also receiving a targeted therapy, such as Herceptin , with chemotherapy, you may continue to receive the targeted therapy for up to a year after completing chemotherapy.
Radiation therapy after surgery can be completed in one to seven weeks.
So, hormonal therapy after surgery takes the longest to complete. Hormonal therapy medicines also can cause troubling side effects, such as hot flashes, night sweats, and joint pain. Less common but more severe side effects include heart problems and blood clots.
Research has shown that about 25% of women who are prescribed hormonal therapy to reduce the risk of recurrence after surgery either dont start taking the medicine or stop taking it early, in many cases because of side effects.
Learn more about Staying on Track With Treatment. You can read about why its so important to stick to your treatment plan, as well as ways to manage side effects after radiation, chemotherapy, and hormonal therapy.
What Increases The Risk Of Invasive Breast Cancer
Thereâs no way to know if youâll develop an invasive form of breast cancer, but there are things that increase your chances, many of which you canât change.
Older women are at higher risk. About 10% of women diagnosed with invasive breast cancer are under age 45. And 2 out of every 3 women with invasive breast cancer are age 55 or older when theyâre first diagnosed.
Your genetics and family history of breast cancer play roles. Itâs more common among white women than black, Asian, or Hispanic women.
Also, youâre at higher risk if youâre obese, your breasts are dense, you didnât have children, or you became pregnant after the age of 35.
Not Diagnosed But Worried
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Breast cancer symptoms vary widely. According to the American Cancer Society, in addition to a lump, breast cancer symptoms can include swelling, skin irritation, dimpling, breast pain, changes to the nipple, thickening of the breast skin, or unusual nipple discharge. Still, some breast cancers cause no symptoms at all. Note: Please do not post pictures of your symptoms. It’s important to have anything unusual checked by your doctor
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Compensatory Crosstalk Between Signaling Pathways
Upregulation of parallel oncogenic pathways can compensate for ER blockade . Using a genome-wide CRISPR/Cas9 screen on estrogen-deprived ER+ cell lines, Xiao et al. identified C-terminal Src kinase as one of the top tumor suppressors whose deletion restored cell growth in the absence of estrogen. The authors demonstrated that E2-bound ER activates the transcription of CSK to create a negative feedback loop that inhibits the oncogenic function of Src family tyrosine kinases /PAK2 via inhibitory phosphorylation. However, endocrine therapy disrupts this estrogen-induced negative feedback, leading to SFKs/PAK2 hyperactivation and worse clinical outcome. The combination of ER antagonists with a PAK2 inhibitor achieved durable suppression of ER+ xenograft growth .
What Is Invasive Lobular Carcinoma
Invasive lobular carcinoma is a cancer that starts in the breasts lobules and invades surrounding tissue. ILC is the second most common form of invasive breast cancer, accounting for 10 to 15% of breast cancer cases. ILC doesnt always form a lump, but women who have it may notice a thick or full area that doesnt feel like the rest of the breast.
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What Are The Signs Of Invasive Breast Cancer
- A lump or thickening in or near the breast or in the underarm that continues after your monthly menstrual cycle
- A mass or lump, which may feel as small as a pea
- A change in the size, shape, or contour of the breast
- A blood-stained or clear fluid from the nipple
- A change in the feel or appearance of the skin on the breast or nipple — dimpled, puckered, scaly, or inflamed
- Redness of the skin on the breast or nipple
- A change in shape or position of the nipple
- An area that is distinctly different from any other area on either breast
- A marble-like hardened area under the skin
You may notice changes when you do a monthly breast self-exam. By doing a regular self-check of your breast, you can become familiar with the normal changes in your breasts.
The Overall Hormone Receptor Status Of A Breast Tumor Helps Predict Behaviour And Responsiveness To Treatment
Indeed, specialists consider the hormone-receptor status of a tumor to be more of a predictive factor rather than a prognostic factor. It helps determine what you are up against, and how best to treat it.
However, research shows that the outlook for a particular breast cancer is more likely to be influenced by the histological type and grade of the breast cancer tumor at the time of discovery.
Also, whether or not there is lymphatic involvement is another important factor, and not the hormone receptor status.
It is true, however, that breast cancer tumors with a positive hormone receptor status have a more indolent course than do hormone receptor-negative tumors.
Indolent is kind of a strange term to use, but it means that a tumor is less responsive or lazy in response to treatment than hormone negative receptor status tumors. Some kind of extra intervention or boost is often necessary to really get a positive healing response from cancer.
However, the good news is that certain kinds of hormone-receptor-positive tumors are actually more responsive to endocrine therapy. So, there is a positive aspect to this as well.
In fact, there is often a kind of inverse relationship between the HER-2 hormone receptor status, and the ER and PR status of a tumor.
Alterations In Er And Aromatase
While the LBD mutations reduce the potency of fulvestrant , next-generation oral SERMs or SERDs that target both WT and mutant ER are in clinical development . For example, GDC-9545 and elacestrant are oral SERDs that have shown preliminary clinical activity in ESR1-mutant MBCs, some of which had progressed on prior SERDs these agents demonstrated acceptable toxicity profiles . Similarly, the oral SERD AZD9496 reduced on-treatment ESR1-mutant ctDNA levels and GDC-0810 reduced 18F-fluoroestradiol uptake by positron emission tomography in patients with ESR1 mutations . The selective estrogen receptor covalent antagonist H3B-6545 covalently binds the Cys530 residue of both WT and mutant ER, enforcing an irreversible antagonist conformation .
Why Do I Need An Er/pr Test
You may need this test if you’ve been diagnosed with breast cancer. Knowing your hormone receptor status will help your health care provider decide how to treat it. If you have ER-positive, PR-positive, or HR-positive cancer, drugs that lower hormone levels or stop the hormones from fueling cancer growth can be very effective. If you have HR-negative cancer, these types of drugs won’t work for you.
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Will I Need To Do Anything To Prepare For The Test
You won’t need any special preparations if you are getting local anesthesia . If you are getting general anesthesia, you will probably need to fast for several hours before surgery. Your surgeon will give you more specific instructions. Also, if you are getting a sedative or general anesthesia, be sure to arrange for someone to drive you home. You may be groggy and confused after you wake up from the procedure.
Optimizing Breast Cancer Therapy
As advances in breast cancer surgery and other modalities occur, we will continue to reevaluate whether we can de-escalate treatment approaches to lessen the burden of treatment for patients.
At MSK, we adopted the no ink on tumor consensus guideline early and conducted a study to confirm the benefits for our patients. We also pioneered the de-escalation of axillary dissection in women with invasive breast cancer and sentinel node metastasis following evidence that found no difference in overall survival or nodal recurrence between sentinel lymph node biopsy and complete axillary lymph node dissection.
The diagnosis and treatment of invasive breast cancer requires a collaborative, multidisciplinary approach. At MSK, the breast cancer team evaluates more than 4,500 new breast cancer cases and sees 3,300 surgical inpatients and outpatients annually. Our objective is to create the most effective individualized treatment plan for each patient to optimize outcomes, reduce the burden of treatment, and improve quality of life.
Monica Morrow, MD, FACS, Chief, Breast Service, Department of Surgery, and Anne Burnett Windfohr, Chair, Clinical Oncology, discuss MSKs evidence-based, leading-edge breast cancer surgical program.
Disclosure: Dr. Morrow has received honoraria from Genomic Health and Roche.
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Is There Anything Else I Need To Know About Er/pr Tests
HER2 testing is often done at the same time as ER/PR testing. That is because some hormone receptor cancers are also HER2-positive. HER2 is a protein found on the surface of all breast cells. Treatments for HER2-positive breast cancer can be very effective but are not effective for HER2-negative cancers.
Limitations Of Her2 Testing
Before the implementation of the first 2007 ASCO/CAP HER2 testing guidelines, the number of patients with equivocal HER2 test results was rather large.
Since 2007, the quality of HER2 testing has improved the frequency of equivocal and inaccurate results has decreased. These improvements are believed to be due in part to the implementation of the testing guidelines since 2007.
With the increasing number of laboratories performing HER2 testing, uniform standards and quality control are mandatory.
The updated 2013 ASCO/CAP guidelines contain even more detailed recommendations on what physicians should discuss with their patients regarding HER2 status reasons for HER2 testing types of tests used interpretation of test results, and any potential need for re-testing in the case of disease recurrence .
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Regulators Of Gene Expression
Razavi et al. found enrichment of alterations in the transcriptional regulators MYC, FOXA1, CTCF, and TBX3 in endocrine-resistant MBCs. These were mutually exclusive with alterations in ESR1 or MAPK pathway components. Alterations in MYC, FOXA1, and CTCF were found to be either pre-existing or acquired following endocrine therapy . A Myc activation signature was previously associated with endocrine resistance in long-term estrogen-deprived cells and poor response to tamoxifen in patients . CTCF is a transcriptional repressor of Myc , suggesting CTCF loss-of-function mutations may lead to Myc upregulation. Decreasing Myc expression with BET inhibitors may be a potential strategy to overcome resistance in tumors with MYC or CTCF alterations . Recent studies have demonstrated that direct targeting of Myc may also be possible . FOXA1 is a pioneering factor involved in chromatin remodeling and has been shown to cooperate with ER to induce gene expression . Thus, tumors with FOXA1 mutations may still rely on ER protein expression and hence remain sensitive to SERDs. However, promoter hotspot mutations in FOXA1 that increased FOXA1 expression were associated with reduced sensitivity to fulvestrant .
More Information About The Tnm Staging System
The T category describes the original tumor:
- TX means the tumor can’t be assessed.
- T0 means there isn’t any evidence of the primary tumor.
- Tis means the cancer is “in situ” .
- T1, T2, T3, T4: These numbers are based on the size of the tumor and the extent to which it has grown into neighboring breast tissue. The higher the T number, the larger the tumor and/or the more it may have grown into the breast tissue.
The N category describes whether or not the cancer has reached nearby lymph nodes:
- NX means the nearby lymph nodes can’t be assessed, for example, if they were previously removed.
- N0 means nearby lymph nodes do not contain cancer.
- N1, N2, N3: These numbers are based on the number of lymph nodes involved and how much cancer is found in them. The higher the N number, the greater the extent of the lymph node involvement.
The M category tells whether or not there is evidence that the cancer has traveled to other parts of the body:
- MX means metastasis can’t be assessed.
- M0 means there is no distant metastasis.
- M1 means that distant metastasis is present.
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Can Hormone Therapy Be Used To Prevent Breast Cancer
Yes. Most breast cancers are ER positive, and clinical trials have tested whether hormone therapy can be used to prevent breast cancer in women who are at increased risk of developing the disease.
A large NCI-sponsored randomized clinical trial called the Breast Cancer Prevention Trial found that tamoxifen, taken for 5 years, reduces the risk of developing invasive breast cancer by about 50% in postmenopausal women who were at increased risk . Long-term follow-up of another randomized trial, the International Breast Cancer Intervention Study I, found that 5 years of tamoxifen treatment reduces the incidence of breast cancer for at least 20 years . A subsequent large randomized trial, the Study of Tamoxifen and Raloxifene, which was also sponsored by NCI, found that 5 years of raloxifene reduces breast cancer risk in such women by about 38% .
As a result of these trials, both tamoxifen and raloxifene have been approved by the FDA to reduce the risk of developing breast cancer in women at high risk of the disease. Tamoxifen is approved for this use regardless of menopausal status. Raloxifene is approved for use only in postmenopausal women.
All About Er Positive Her2 Negative Breast Cancer
About one in eight women in the United States will develop breast cancer, according to commonly used statistics.
But other reports indicate that breast cancer rates are on the decline, likely because of improved recognition, prevention, and treatment. One advancement is the ability to identify different breast cancer types based on specific molecules found in tumors. The distinction greatly aids in breast cancer treatment selection and helps doctors predict how aggressive cancers will advance.
A crucial step in the process of beast cancer evaluation is testing tumor tissue removed during a biopsy or surgery to determine if it has estrogen and progesterone receptors molecules that the hormones bind to.
Cancerous cells may have none, one, or both receptors. Breast cancers that have estrogen receptors are called ER-positive . Those with progesterone receptors are referred to as PR-positive .
In addition to hormone receptors, some breast cancers have high levels of a growth-promoting protein called HER2/neu. If a tumor has this property, it is called HER2-positive. HER2 positive cancers are more aggressive than HER2 negative cancer.
Knowing breast cancer type, leads doctors to determining best treatments.
HER2 negative cancers will not respond to treatment with drugs that target HER2, such as trastuzumab and lapatinib .
Overall, estrogen receptor-positive breast cancer is treatable, especially when diagnosed early.
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Questions To Ask About Your Breast Cancer Diagnosis
Being diagnosed with cancer or any major illness is overwhelming and confusing. You dont know what questions to ask when you walk into a doctors office. Here are seven questions to ask your oncologist about your diagnosis so you can understand your stage, prognosis and treatment options:
1. What type of breast cancer do I have?
Not all breast cancers are the same. Doctors classify them in a number of different ways. Probably the most basic is where the cancer cells originate. Their origin is a factor in whether your cancer may spread and helps decide the kind of treatment youll get. Most breast cancers 70 to 80 percent start in the milk ducts. Theyre known as infiltrating or invasive ductal carcinomas, meaning theyve broken through the milk ducts wall and have proliferated into the breasts fatty tissue. Ten percent of breast cancers start in the milk-producing glands, or lobules, and are called invasive lobular carcinomas. Theyre also capable of spreading. Some breast cancers are non-invasive, meaning they havent spread. Theyre contained within the milk ducts and are called ductal carcinoma in situ, or DCIS.
2. How big is my tumor?
Tumor size is another factor that will determine your course of treatment. The tumors dimensions are estimated by a physical exam, mammogram and an ultrasound or MRI of the breast. The precise size wont be known until a pathologist studies the tumor after surgical removal.
3. Is the cancer in my lymph nodes?
Some Proteins Make Breast Tumors More Receptive To Certain Hormones
Sometimes medics use the phrase hormone receptor status along with terms like protein status and HER-2 status. These are all related terms because the presence of certain proteins is what makes a tumor more receptive to certain hormones.
Some hormones affect growth rates, such as the hormones attracted by HER-2 proteins. However, other hormones might suppress growth or actually aid with healing and blood flow.
The hormone receptor status of a tumor is a composite of all the different proteins that might influence the behaviour of a particular tumor in a particular patient. So, the HER-2 status is a small subset of the overall hormonal picture, that specifically rates to the probable growth rate of the new cancer cells.
HER-2 gene amplification in breast cancer:-
- reduces apoptosis
- means more progressive regional and distant metastases.
So, breast cancers presenting with a higher-than-average or positive HER-2 status will almost certainly be more aggressive.
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What Are Estrogen Receptor/progesterone Receptor Tests
Estrogen receptor/progesterone receptor tests are used to help guide breast cancer treatment. Receptors are proteins that attach to certain substances. ER/PR tests look for receptors that attach to the hormones estrogen and progesterone in a sample of breast cancer tissue. Estrogen and progesterone play key roles in a woman’s sexual development and reproductive functions. Men also have these hormones, but in much smaller amounts.
About 70 percent of all breast cancers in women have receptors that attach to estrogen and/or progesterone. About 80 percent to 90 percent of breast cancers in men have these receptors. Breast cancers with estrogen and/or progesterone receptors include the following types:
- ER-positive : Cancers that have estrogen receptors
- PR-positive : Cancers that have progesterone receptors
- Hormone receptor-positive : Cancers that have one or both types of these receptors.
Breast cancers without ER or PR receptors are known as HR-negative .
ER/PR tests will show whether there are ER and/or PR receptors on your breast cancer cells. Test results are frequently referred to as the hormone receptor status. If your hormone receptor status shows you have one or both of these receptors on your cancer cells, you may respond well to certain types of treatments.
Other names: ER/PR IHC testing, hormone receptor status