Sunday, February 25, 2024

What Causes Her2-positive Breast Cancer

The Details: In Depth Analysis Of The Impact Of Anti


Research data set forth above has illustrated the current status of anti-HER2 therapy in China and in the USA. Will the adoption of targeted therapy for HER2-positive breast cancer affect the survival of patients, and if so, how much is the impact? We will look for answers through clinical data and analysis on real-world treatment conditions.

How Long Does It Take To Recur With Trastuzumab

The mean age in the cohort was 49.5 years, and the median time to recurrence or death was 2.5 years for patients without an event, the median follow-up time was 8.0 years. A total of 54.5% of patients had HR-positive disease, and 48.0% of all patients were treated with adjuvant trastuzumab-based chemotherapy.

What Happens During A Her2 Breast Cancer Test

Most HER2 testing involves taking a sample of tumor tissue in a procedure called a biopsy. There are three main types of biopsy procedures:

  • Fine needle aspiration biopsy, which uses a very thin needle to remove a sample of breast cells or fluid
  • Core needle biopsy, which uses a larger needle to remove a sample
  • Surgical biopsy, which removes a sample in a minor, outpatient procedure

Fine needle aspiration and core needle biopsies usually include the following steps:

  • You will lay on your side or sit on an exam table.
  • A health care provider will clean the biopsy site and inject it with an anesthetic so you won’t feel any pain during the procedure.
  • Once the area is numb, the provider will insert either a fine aspiration needle or core biopsy needle into the biopsy site and remove a sample of tissue or fluid.
  • You may feel a little pressure when the sample is withdrawn.
  • Pressure will be applied to the biopsy site until the bleeding stops.
  • Your provider will apply a sterile bandage at the biopsy site.

In a surgical biopsy, a surgeon will make a small cut in your skin to remove all or part of a breast lump. A surgical biopsy is sometimes done if the lump can’t be reached with a needle biopsy. Surgical biopsies usually include the following steps.

  • Once the biopsy area is numb or you are unconscious, the surgeon will make a small cut into the breast and remove part or all of a lump. Some tissue around the lump may also be removed.
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    Time To Brain Metastasis And Timing Of Brain Metastasis

    The median TTBM was 30.1 months for all patients. BM occurred significantly later in patients who received anti-HER2 treatment before BM compared with those who did not . Brain was the first site of metastasis in 62 patients. Patients who received adjuvant trastuzumab were more likely to present with brain as the first site of metastasis than those who did not .

    Blocking Her2 Slows Or Stops Some Types Of Breast Cancer

    Adjuvant Pertuzumab and Trastuzumab in Early HER2

    NCI-funded researcher Dennis Slamon, M.D., was among the many scientists searching for genes that can lead to cancer. In 1987, he and his colleagues discovered that the growth factor receptor gene HER2, which produces HER2 proteins, might be a good candidate.

    At the same time, a team of NCI researchers led by Stuart Aaronson, M.D., were among the first to show that the HER2 protein could cause normal cells to grow uncontrollably like aggressive cancer cells.

    Dr. Slamons team found that the HER2 protein is present at high levels in about 30 percent of breast cancers. They also discovered that high levels of HER2 are linked to a greater likelihood of metastasis and relapse and an overall decrease in patient survival. The group concluded that HER2 might play a role in the development and growth of breast cancer.

    NCI-funded researcher Dennis J. Slamon, M.D., discovered the genetic link between HER2 and breast cancer.

    This led researchers to a groundbreaking hypothesis: If HER2 could be blocked, the growth of HER2-positive breast cancer might be slowed.

    One way to block the action of a protein is to use laboratory-made monoclonal antibodies that attach to a specific protein and disrupt its function. With NCI support, Dr. Slamon and colleagues from the University of Texas Health Sciences Center had a breakthrough. They showed that an antibody specific to HER2 could slow the growth of metastatic breast cancer cells and other types of cancer in a laboratory dish.

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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.

    Her2 Positive Breast Cancer Symptoms

    The symptoms of HER2 positive breast cancer are much like the symptoms of other breast malignancies. Most individuals with this form of cancer first notice a hard lump in a breast. Many breast lumpsthe majority, in factare not cancerous, but it is still important to promptly speak with a physician if you notice a lump in one of your breasts.

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    The Meaning Of The Test Results

    In most cases, the cancerâs HER2 status will first be checked using the IHC test. Possible results from the IHC test include:

    • HER2-negative: an IHC score of 0 or 1+. HER2-targeted therapy will not be effective. Your treatment will be based on other characteristics of the cancer, such as the hormone receptor status.
    • Equivocal, or borderline: an IHC score of 2+. This cancer is considered equivocal, meaning the results are uncertain. Some doctors may refer to this as borderline. If the cancer tests as 2+, youâll need further testing to know your HER2 status and whether HER2-targeting therapies are an option for you.
    • HER2-positive: an IHC score of 3+. HER2-targeted therapies are very effective in treating this cancer.

    If the tumor is sent for ISH testing, the results reflect the number of extra copies of HER2 genes found in the breast cancer cells and whether the cells have more than one chromosome 17, shown as HER2/CEP17 ratio. Chromosome 17 is where the HER2 gene is located. The results of the ratio as well as the number of HER2 genes will help your doctor decide whether the tumor is ultimately considered HER2-positive or HER2-negative.

    Loss Or Masking Of Her2 Epitope

    HER2-Positive Breast CancerReduce Your Risk of Recurrence | Access Health

    The presence of p95HER2 has been associated with poor outcomes in patients with HER2+ EBC, and patients with MBC overexpressing p95HER2 had lower response rates to trastuzumab than those expressing full-length HER2 . Chemotherapy sensitized p95HER2/611CTF xenografts to trastuzumab, presumably via HER2 stabilization induced by chemotherapy. Lapatinib inhibited p95HER2 phosphorylation in cell lines, reducing downstream activation of AKT and MAPK and inhibiting cell growth. Retrospective analyses from clinical trials with lapatinib noted that the presence of p95HER2 had no influence on lapatinib efficacy. Similarly, in the CHER-LOB neoadjuvant study, which randomized patients to receive trastuzumab, lapatinib or their combination, p95HER2 expression was not predictive of outcome nor did it predict for sensitivity to either anti-HER2 agent. Therefore, the role of p95HER2 as a biomarker of resistance or sensitivity remains to be confirmed.

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    Current Status Of Anti

    Professor Liu Guangyu, Fudan University Cancer Hospital, has pointed out that, there is a lack of large-scale data on our anti-HER2 treatment of HER2-positive breast cancer patients. A 2011 study published in the Journal of Cancer Research China reported data on the anti-HER2 therapy for HER2-positive breast cancer patients in the Beijing area in 2008 the results showed that only 20% HER2-positive patients received a targeted therapy. A 2014 study published in the Lancet Oncology also showed that, in spite of trastuzumab being listed in China in 2002, only 20.6% of HER2-positive breast cancer patients received the anti-HER2 therapy in Beijing .

    To further understand the current status of anti-HER2 therapy in breast cancer patients and fight for the benefit of survival for patients, CBCS launched a large-scale survey named the Goddess Project . The study carried out a nationwide survey on the rate of adjuvant anti-HER2 targeted therapy for HER2-positive breast cancer patients, including summary analysis of the rate of targeted treatment to factors of patient age, TNM stage, and hormone receptor expression.

    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.

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    Treatment For Her2 Positive Breast Cancer

    HER2 positive breast cancer life expectancy is affected by many factors, including the stage at diagnosis and the treatment used. However, several effective HER2 positive breast cancer treatmentsare available for this subtype and your doctor will choose the right one/s for you based on several factors .

    For most people,HER2 positive breast cancer treatment involves targeted therapies drugs that specifically aim to block HER2 protein to stop the cancer cells from growing. Patients with HER2 positive breast cancer may also receive a combination of treatments that may include surgery, radiation, chemotherapy, targeted and hormonal therapies . The drugs used for patients with HER2 positive breast cancer may include:

    Who May Not Be Able To Have Herceptin

    Absence of integrin α3β1 promotes the progression of HER2

    Herceptin should not be used to treat people with breast, oesophageal or stomach cancer that is not HER2 positive.

    It may also not be suitable if:

    • you have a pre-existing heart condition, such as heart failure, severe angina or a problem with your heart valves
    • you have poorly controlled high blood pressure
    • you’re pregnant
    • you’re breastfeeding

    Avoid becoming pregnant while taking herceptin and for at least 7 months after treatment stops, as it could harm your developing baby.

    Also avoid breastfeeding until at least 7 months after treatment stops, as the medicine can enter breast milk and may be harmful for babies.

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    Overall Survival After Brain Metastasis

    At the end of the study period, 61.8% had died, of which 54.9% died due to complications of brain metastases. The median OS after BM was 10.9 months for all patients. OS after BM was significantly longer in patients who received anti-HER2 treatment after BM than those who did not . The greatest survival benefit was observed in patients who received both trastuzumab and lapatinib, followed by lapatinib alone , trastuzumab alone , and without anti-HER2 treatment .

    Overall survival after brain metastasis by anti-HER2 treatment received after diagnosis of brain metastasis . Anti-HER2 treatment vs no anti-HER2 treatment. Median OS after BM for all patients was 10.9 months . Both agents vs lapatinib only vs trastuzumab only vs no anti-HER2 treatment. Median OS after BM for all patients was 10.9 months . *Trastuzumab and lapatinib given sequentially or concomitantly.

    Her2s Genetic Link To Breast Cancer Spurs Development Of New Treatments

    Single breast cancer cell and microenviornment visualized by transparent tumor tomography.

    When NCI-supported researchers discovered that the HER2 gene is important for breast cancer growth, this led to the development of the drug trastuzumab and other targeted treatments that have improved survival for women with HER2-positive breast cancer.

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    Box 3 Toxicities With Her2

    Although highly effective in disease control and improving survival, approved anti-HER2 therapies are not without potential adverse events , some of which require careful monitoring.

    Cardiotoxicity. Cardiac dysfunction with trastuzumab is an AE of concern in the metastatic breast cancer and early breast cancer settings, particularly when given in combination with anthracyclines,. Dual HER2-targeted therapy with pertuzumab and trastuzumab in HER2+ MBC has not been shown to exacerbate cardiotoxicity or lead to increased cardiac events after long-term follow-up in the adjuvant setting,.

    • Trastuzumab-induced cardiotoxicity is usually asymptomatic, not related to cumulative dose and largely reversible.

    • Numerous measurements of left ventricular ejection fraction during trastuzumab therapy may lead to false positive elevations.

    • Increased rates of cardiotoxicity have not been observed in long-term follow-up,.

    • The FDA recommends baseline LVEF evaluation before initiating trastuzumab.

    • Cardiac monitoring strategies have been developed by the American Society of Clinical Oncology and the European Society for Medical Oncology ,.

    Gastrointestinal toxicity. Gastrointestinal toxicities and rash are frequently observed with tyrosine kinase inhibitors , primarily due to epidermal growth factor receptor targeting.

    Liver toxicity. Elevated liver enzymes are commonly reported with ado-trastuzumab emtansine and tucatinib,,.

    • Mitigation strategies include dose interruptions and dose modifications.

    What Do The Results Mean

    Reduce the Risk of Recurrence in Early Stage HER2 Breast Cancer

    If HER2 protein levels are higher than normal or extra copies of the HER2 gene are found, it probably means you have HER2-positive cancer. If your results show normal amounts of HER2 protein or the normal number HER2 genes, you probably have HER2-negative cancer.

    If your results were not clearly positive or negative, you will probably get retested, either using a different tumor sample or using a different testing method. Most often, IHC is done first, followed by FISH . IHC testing is less expensive and provides faster results than FISH. But most breast specialists think FISH testing is more accurate.

    Treatments for HER2-positive breast cancer can substantially shrink cancerous tumors, with very few side effects. These treatments are not effective in HER2-negative cancers.

    If you are being treated for HER2-positive cancer, normal results may mean you are responding to treatment. Results that show higher than normal amounts may mean your treatment is not working, or that cancer has come back after treatment.

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    Her2 Positive Breast Cancer: What It Is Diagnosis And Treatment

    The human epidermal growth factor 2 also known as HER2 is a protein that tells human cells when to grow and when not to grow. Sometimes, a random genetic mutation or extra copies of the gene that encodes HER2 make these cells grow even when they shouldnt.

    This type of cancer is called HER2 positive. Because it grows more quickly, its more aggressive than other cancers. Bladder cancer, gastrointestinal cancers, ovarian cancer and stomach cancer can also be HER2 positive.

    About 20% of breast cancer diagnoses are HER2 positive, but its not clear why this develops or who is most at risk.

    Debu Tripathy, M.D., has been studying and treating HER2 positive breast cancer since the 1980s. We spoke to him about what makes HER2 positive breast cancer different and how to get an accurate diagnosis to ensure more effective treatment.

    How is HER2 positive breast cancer diagnosed?

    HER2 positive breast cancer has the same symptoms as other types of breast cancer. Patients often find a lump, or a routine mammogram spots one. Inflammatory breast cancer can also be HER2 positive, so patients may notice a rash or other breast changes.

    To know for sure if the cancer is HER2 positive, your care team will take a biopsy and examine cancerous cells more closely. There are two tests used to determine HER2 status:

    What are the treatment options for HER2 positive breast cancer?

    Treatment for HER2 positive breast cancer depends on the tumors size.

    Breast Cancer Research At Moffitt Cancer Center

    Moffitt Cancer Center has been designated a Comprehensive Cancer Center by the National Cancer Institute, an achievement that speaks directly to our commitment to advancing research and treatment for this malignancy. We are researching the causes of HER2 positive breast cancer every day, and we wont be satisfied until there is a cure. To advance the treatment of this malignancy, Moffitt spearheads a robust clinical trials program where eligible patients can receive the latest breakthroughs in treatment before they are available elsewhere.

    If you would like to learn more about the causes of HER2 positive breast cancer, or if you have been diagnosed with this malignancy and would like to explore the treatment options available to you at Moffitt, we encourage you to request an appointment. To do so, call or submit a new patient registration form. We accept patients with or without referrals.

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    Causes And Risk Factors Of Her2 Positive Breast Cancer

    There are several lifestyle, environmental and genetic risk factors for breast cancers, including HER2 positive breast cancer.

    • HER2 breast cancer is not hereditary. It is caused by the excess production of HER2 protein.
    • The risk of breast cancer in general increases if you have breast cancer cases in the family.
    • Being overweight or obese increases the risk of developing breast cancer in post-menopausal women, including HER2 breast cancer.
    • Living a sedentary lifestyle, smoking, and drinking alcohol can also increase an individuals risk of developing breast cancer.
    • Other risk factors may include ageing, previous breast cancer diagnoses, having dense breasts , having radiation to the chest area before the age of 30, beginning menstruation before age 12, and having mutations of genes such as BRCA1, BRCA2as well as less common mutations in PTEN, PALB2, CHEK2, ATM, CDH1 and P53.

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