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.
Q: How Do You Offer Support To Others These Days
A: I believe that every day is a gift and I try to give back to others constantly. I enjoy telling my story, which includes not only the importance of faith and prayer, but also important information about the BRCA mutation, a genetic disorder most common among Jewish women of Ashkenazic ancestry. I’ve written a chapter for the book edited by Rabbi Douglas Kohn and published by URJ Press Life, Faith, and Cancer. In the book, I tell about a very special and unique ceremony I had at the conclusion of my chemo treatments.
Is The Cancer In My Lymph Nodes
Whether your breast cancer has spread to your lymph nodes the filtering mechanisms in your armpits and elsewhere in the body that are part of the immune system is one of the most important predictors of the severity of your disease.
Involvement of the lymph nodes changes the treatment plan, says Dr. Abraham. When breast cancer cells have spread to the lymph nodes, we tend to discuss more aggressive treatment options, such as chemotherapy.
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Q: Talk To Me A Little About Your Diagnosis And Treatments
A: I was diagnosed with breast cancer in 2001. As a result of having advanced breast cancer – stage 3 C invasive ductal carcinoma, in the past eight years I’ve had several cancer surgeries, including a bilateral mastectomy, bilateral oopherectomy, three different types of chemotherapy over 64 weeks, five weeks of daily radiation, lymphedema, and numerous bouts of cellulitis, a life-threatening infection.
Despite the odds against me, I’ve known how to live each day as if it were my last.
A Few Thoughts On Olivia Newton
The words celebrities use carry an enormous amount of weight.
This past week, in a televised interview, Olivia Newton-John spoke about her life with cancer. In the past, she has named her cancer as a return, or metastasis, of the breast cancer she was initially treated for two decades earlier.
Whenever there is further spread, or progression, of breast cancer outside of the breast it means that efforts to control the cancer have failed, at least for the moment. Yet, as the news spread around the globe, I felt that outlets didnt share the most basic facts about metastatic cancer. Instead, as in USA Today, the headline was Olivia Newton-John Diagnosed With Cancer For The Third Time.
On Good Morning America, cancer survivor and host Robin Roberts and Dr. Jennifer Ashton explained that cancer can metastasize/recur or there can be a second primary tumor. But in the specific case of Newton-John, who has said that the sites at her shoulder and the base of her spine, are returns of the breast cancer, there is little question that this is metastatic disease. As I watched the GMA clip, I thought it would have been helpful for the hosts to be specific about what metastatic disease is and why this is what Newton-John is facing. Although people can be diagnosed with multiple primary sites of the same or different cancers, when we’re talking about breast cancer that has spread to the bones , it is metastatic cancer.
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Cynthia Nixon Actress Was Diagnosed With Breast Cancer After A Routine Mammogram
Like many celebrities, actress Cynthia Nixon of Sex and the City fame chose not to reveal her breast cancer diagnosis until after the fact. Diagnosed in 2006, she had a lumpectomy and then six and a half weeks of radiation therapy, she told Good Morning America. Nixon, whose mother is also a breast cancer survivor, stated that knowing her personal risk“made me more aware and more empowered when I faced my own diagnosis.” She also joined the Susan G. Komen organization to help educate women around the world about breast cancer.
Emma Watsons Major Hair Chop Made Its Red
Im not signing off, she told Elle in 2020. I feel like Im a very, very healthy human being. Its hard to wrap up your affairs when you feel like youre going to live another 10 or 15 years.
Shes continued to share truthful photos of her cancer journey with her Instagram followers, speaking to both her mental and her physical health, andmost recentlyher decision to shave her head in the face of post-chemotherapy hair loss.
Current Standard Of Care For Her2+ Bc
As the understanding of HER2 biology has evolved , so has the development of agents that target HER2. HER receptors contain an extracellular ligand-binding domain, a transmembrane domain, and an intracellular tyrosine kinase domain. Ligand binding to the HER proteins results in homodimerization or heterodimerization of these receptors, leading to activation of downstream signalling pathways that promote cell division and growth and inhibit apoptosis. There is no known ligand for HER2, but it is a preferred dimerization partner for the other HER proteins, especially HER3 . HER2 overexpression or amplification leads to ligand-independent dimerization and abnormal signalling in addition to increased signalling through ligand-dependent heterodimerization. The efficacy of HER2-targeted agents is most prominent in these HER2-positive tumours.
Since the initial approval of trastuzumab for HER2+ BC, multiple agents exhibiting various mechanisms of action and safety profiles have been approved for the treatment of early-stage and metastatic disease . Below, agents that have been approved by regulatory agencies are briefly described and the advantages and limitations of each strategy are summarized.
Fig. 1: Evolution of HER2 as a biomarker and target for treatment for breast cancer.
Her2+ Breast Cancer Survivor Shares Hope
When Dorothy Paterson discovered a lump in her right breast while showering in 1998, she didnt believe it at first.
I tried to wish it away, but then felt it again the next day, she says. Id had a clear mammogram just the year before, but something was not quite right.
So, Dorothy went to her general practitioner. After a number of tests, he diagnosed her with invasive ductal carcinoma. Dorothy knew exactly what to do next. She had heard positive stories about MD Anderson for years, and several of her friends urged her to make an appointment here immediately.
An HER2+ breast cancer diagnosis
At MD Anderson, Dorothy received additional testing, which revealed she had a particularly aggressive form of breast cancer known as HER2+. The tumor in Dorothys right breast measured 5×8 centimeters . It had reached stage III in less than a year. But MD Anderson offered Dorothy treatment and more importantly, hope.
I will never forget that momentous day, she says. My parents were babysitting on Jan. 15, 1998, when my husband and I went for my first appointment. And when we came home, they were so confused because we were all smiles. My mother asked, So, you don’t have cancer? And I said, Yes, I do. But we have found the right place and the right doctor. He will leave no stone unturned to give me the best quality of care possible.
Starting breast cancer treatment at MD Anderson
Dealing with breast cancer treatment side effects
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Sandra Lee Celebrity Chef Was Diagnosed With Ductal Carcinoma In Situ
Celebrity chef Sandra Lee announced in May 2015 that she had been diagnosed with ductal carcinoma in situ at age 48 following a routine screening mammogram. She initially had a lumpectomy to treat it, but, as Lee told Good Morning America coanchor Robin Roberts in an interview, When the lumpectomy was done, they did not have clean margins. Lee reported being told she was a ticking time bomb, and she was advised to have a double mastectomy, which she did.
The longtime partner of New York State Governor Andrew Cuomo, Lee spoke out strongly in favor of starting screening mammograms early, in a womans twenties or thirties, and not waiting until age 50, as is recommended for most women by the U.S. Preventive Services Task Force. If I would have waited, she said, I probably wouldn’t even be sitting here.
Lee experienced complications following her mastectomies and required a second surgery to treat an infection.
Shannen Doherty Actress Is Working Through Advanced Breast Cancer
In August 2015, actress Shannen Doherty, best known for her roles on the shows Beverly Hills, 90210 and Charmed, confirmed to People magazine that she was being treated for breast cancer. The news came out after it was reported on TMZ that Doherty was suing her former business manager for failing to pay her health insurance premiums, causing her coverage to lapse and resulting in the cancer being detected at a later stage than it would have been otherwise. According to the lawsuit, the cancer was metastatic to at least one lymph node at the time it was discovered.
Though Doherty stated in April 2017 that she was in remission after surgery, radiation, and chemotherapy, by February 2020 the breast cancer had recurred and reached stage 4 . Speaking about her diagnosis on Good Morning America, she noted that she originally hid the news while filming the 2019 reboot of 90210 because people with stage 4 can work too. … Our life doesnt end the minute we get that diagnosis. We still have some living to do.
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Other Potential Mechanisms Of Resistance
Several other mechanisms of anti-HER2 therapy resistance have recently been elucidated. A study modelling resistance of HER2+ PIK3CA-mutant BC using two patient-derived xenografts, one resistant to paclitaxel and T-DM1 and the other insensitive to T-DM1 and pertuzumab, demonstrated that alveolar epithelial and fibroblastic reticular as well as lymphatic vessel endothelial hyaluronan receptor 1-positive macrophages may be putative drivers of therapeutic resistance. These intriguing findings require further studies comparing data from transcriptome and exome profiling from trials with anti-HER2 therapies. Preclinical studies hint that abnormal transit of T-DM1 through the endosomal maturation pathway may be responsible for resistance to T-DM1 treatment, but this has not been validated or studied in clinical trials.
Three novel markers, RAC1, CDK12 and VTCN1, have been found to correlate with response to lapatinib, neratinib and tucatinib in a study that compared the TKI anti-proliferative effects using a 115-cancer cell line panel to identify novel markers of TKI response and/or resistance markers. Prior data have implicated these genes in resistance to anti-HER2 therapies or immunotherapy,,. Hence, combinations of HER2 TKIs and CDK12 and RAC1 inhibitors may offer a therapeutic strategy in high CDK12- or RAC1-expressing HER2+ BC.
Factors That Affect Outlook
When considering your outlook, your doctor must analyze many other factors as well. Among them are:
- Stage at diagnosis. Your outlook is better when the breast cancer hasnt spread outside the breast or has spread only regionally at the start of treatment. Metastatic breast cancer, which is cancer that has spread to distant areas of the body, is harder to treat.
- Size and grade of primary tumor. This indicates how aggressive the cancer is.
- Lymph node involvement. Cancer can spread from the lymph nodes to distant organs and tissues.
- HR status and HER2 status. Targeted therapies can be used for HR-positive and HER2-positive breast cancers.
- Overall health. Other health issues you may have may complicate treatment.
- Response to therapy. Its hard to predict whether a particular therapy will be effective or produce intolerable side effects.
- Age. Younger women and those over age 75 may have a worse outlook than middle-aged women, except for those with stage 3 breast cancer, according to a .
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Prepare For A Career In Oncology Nursing
Search our extensive library for teaching materials such as books and videos.
The Oncology Nursing Society is a professional association that represents 100,000 nurses and is the professional home to more than 35,000 members. ONS is committed to promoting excellence in oncology nursing and the transformation of cancer care. Since 1975, ONS has provided a professional community for oncology nurses, developed evidence-based education programs and treatment information, and advocated for patient care, all in an effort to improve the quality of life and outcomes for patients with cancer and their families.
Will I Need Surgery And What Kind Should I Have
This is an important question but the answer may be less than definitive. It will vary from patient to patient and you may have more than one choice.
According to the American Cancer Society, most women with breast cancer have some type of surgery. But some breast cancers cant initially be surgically removed. In other cases, whether to operate and the type of surgery may depend on the cancers stage, the tumors size and location, the size of your breast and your personal preference.
In women whose breast cancers are operable, the choices are breast-conserving surgery or mastectomy. Mastectomy is the removal of most or all breast tissue and possibly nearby lymph nodes. Within each of those two broad categories are further options. Talk with your oncologist and breast surgeon. If you have any doubts, you may choose to seek a second opinion.
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Host And Tumour Immunity
ADCC is a key mechanism mediating the antitumour activity of trastuzumab, and it can be hampered by an immunosuppressive TME. NK cells have an important role in antitumour immunity, and their activity is regulated by careful modulation of inhibitory and activating receptor signalling. Tumour cells expressing high levels of HLA class I molecules can inhibit NK cells through the engagement of killer cell immunoglobulin-like receptors . HLA-G was shown to desensitize BC cells to trastuzumab by binding to the NK cell receptor KIR2DL4, and blocking this HLA-GKIR2DL4 signalling made HER2+ BC susceptible to trastuzumab treatment in vivo. Moreover, trastuzumab increased the production of TGF and interferon- by BC cells and NK cells, respectively. TGF induced PD1 expression on NK cells, and PD1 blockade significantly increased cytotoxicity of NK cells. Accordingly, combined blockade of HLA-G and PDL1/PD1 may be necessary for effective treatment of trastuzumab-resistant BC.
Jaclyn Smith Actress Discovered Breast Cancer After A Yearly Screening
Actress Jaclyn Smith’s breast cancer was found through her yearly mammogram and led to a lumpectomy and radiation in 2002. One piece of advice she shared with CNN.com is not to go it alone. Although her husband, a doctor himself, was a great source of strength and support, Smith noted, “One of the most important things you can do is remember the power of girlfriends. … Girlfriends saved my day.” In fact, one friend who was particularly helpful to Smith was a breast cancer survivor herself.
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What Do The Test Results Mean
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.
What Are The Symptoms Of Her2
Its not possible to self-determine whether you have HER2-positive breast cancer. If your doctor suspects cancer, further testing will reveal whether you are HER2-positive.
Overall, its important to see your doctor right away if you notice any of the following symptoms:
- any new or changing lumps in your breast or armpit areas
- clear, colored, or bloody nipple discharge
- unexplained pain in your breasts
- changes in your nipples or breast skin, such as dimpling, reddening, or scaliness
- nipples that turn inward
Hormone treatments may be an option for cancer thats also HR-positive.
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Activation Of Compensatory Pathways
The activation of compensatory signalling pathways to overcome effects of trastuzumab treatment has been a subject of extensive exploration. Nearly 2550% of BCs harbour PIK3CA mutations, with enrichment in HR+ and HER2+ subtypes. PIK3CA mutations are associated with reduced pCR rates to neoadjuvant anti-HER2 therapies and decreased efficacy with trastuzumab or pertuzumab in HER2+ MBC,. Loss of PTEN , which leads to hyperactivation of the PI3K pathway, has also been observed in trastuzumab-resistant tumours,. Development of PI3K and mTOR inhibitors offered hope of a therapeutic option, but early trials with buparlisib in the neoadjuvant setting did not yield the desired outcomes. The BOLERO-1 and BOLERO-3 trials evaluated the addition of the mTOR inhibitor everolimus to trastuzumab plus chemotherapy in first-line and trastuzumab-resistant HER2+ MBC settings, respectively. Biomarker analysis from the pooled study populations indicated PI3KAKTmTOR pathway aberrations in approximately 40% of tumours, with everolimus treatment leading to a consistent benefit in these patients versus patients with tumours not exhibiting the aberrations. Although these results suggested proof of concept, the triplet combinations led to increased toxicity. The advent of isoform-specific PI3K inhibitors such as alpelisib has led to a maintenance study of triplet alpelisib-trastuzumab-pertuzumab in patients with PIK3CA-mutant HER2+ MBC .