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Her2-positive Breast Cancer Treatment Guidelines 2021

Clinicopathological Characteristics Of Patients With T2 Gbc

Metastatic HER2-Positive Breast Cancer: Newer and Emerging Treatment Considerations

Of 90 patients with T2 GBC, 51.1% were female and 48.9% were male. The mean age was 68.3±9.2 years and the percentage of patients over 65 years of age was 64.4% . We identified 83 and 7 cases with well to moderately and poorly differentiated tumors, respectively. Lymph node metastasis occurred in 20 patients . The median duration of follow-up after surgery was 64.5±40.4 months . During this period,

Targeted Therapy For Her2

In about 15% to 20% of breast cancers, the cancer cells make too much of a growth-promoting protein known as HER2 . These cancers, known as HER2-positive breastcancers, tend to grow and spread more aggressively than HER2-negative breast cancers. Different types of drugs have been developed that target the HER2 protein.

Stage Information For Breast Cancer

In This Section

The American Joint Committee on Cancer staging system provides astrategy for grouping patients with respect to prognosis. Therapeuticdecisions are formulated in part according to staging categories but also according to other clinical factors such as the following, some of which are included in the determination of stage:

  • Estrogen-receptor and progesterone-receptorlevels in the tumor tissue.
  • Human epidermal growth factor receptor 2 status in the tumor.
  • General health of thepatient.

The standards used to define biomarker status are described as follows:

  • Estrogen receptor expression: ER expression is measured primarily by immunohistochemistry . Any staining of 1% of cells or more is considered positive for ER.
  • Progesterone receptor expression: PR expression is measured primarily by IHC. Any staining of 1% of cells or more is considered positive for PR.
  • HER2 expression: HER2 is measured primarily by either IHC to assess expression of the HER2 protein or by in situ hybridization to assess gene copy number. The American Society of Clinical Oncology/College of American Pathologists consensus panel has published guidelines for cases when either IHC or ISH testing is equivocal.

    IHC:

  • Negative: 0 or 1+ staining
  • Equivocal: 2+ staining
  • Possible negative results:
  • HER2/chromosome enumeration probe ratio < 2.0 ANDHER2 copy number < 4
  • Possible equivocal results:
  • HER2/CEP17 ratio < 2.0 ANDHER2 copy number 4 but < 6
  • ISH :

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    Neoadjuvant Therapy Of Her2+ Bc: State Of The Art

    Neoadjuvant treatment was long reserved for patients with inoperable, locally advanced or inflammatory BC, with the aim of making the tumor operable and also of improving the surgical rates and quality. Furthermore, one of the key objectives of neoadjuvant chemotherapy was the clinical and pathological downstaging of positive axillary lymph nodes. Randomized clinical trials performed in the 1980s and 1990s demonstrated the same survival benefit for chemotherapy administered as neoadjuvant therapy or as adjuvant therapy. Since then, the approach to neoadjuvant treatment has changed and treatment decisions are currently based on the tumor biology and tumor stage. In the context of operable disease, most patients with HER2-positive tumors measuring > 1 cm and/or node-positive disease undergo neoadjuvant treatment . In Italy, the main indications for neoadjuvant chemotherapy currently include the following: locally advanced BC , since in most cases these are not susceptible to conservative surgery and because of the higher risk of relapse early-stage BC if conservative surgery is not feasible, for example, due to a high tumorbreast ratio or if the expected cosmetic outcome is suboptimal due to the particular tumor location.

    Ajcc Pathological Prognostic Stage Groups

    Metastatic Breast Cancer (MBC) : Odonate

    The Pathological Prognostic Stage applies to patients with invasive breast cancer initially treated with surgery. It includes all information used for clinical staging, surgical findings, and pathological findings following surgery to remove the tumor. Pathological Prognostic Stage is not used for patients treated with neoadjuvant therapy before surgery to remove the tumor.

    References
  • Barnes DM, Harris WH, Smith P, et al.: Immunohistochemical determination of oestrogen receptor: comparison of different methods of assessment of staining and correlation with clinical outcome of breast cancer patients. Br J Cancer 74 : 1445-51, 1996.
  • Wolff AC, Hammond MEH, Allison KH, et al.: Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol 36 : 2105-2122, 2018.
  • Breast. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer 2017, pp. 589628.
  • Wolff AC, Hammond ME, Hicks DG, et al.: Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 31 : 3997-4013, 2013.
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    Treatment In The First

    The CLEOPATRA trial examined the addition of pertuzumab to the doublet trastuzumab + docetaxel as first-line treatment in patients with HER2-positive metastatic breast cancer . Results demonstrated an improvement in median progression-free survival and an even greater improvement in overall survival with the addition of pertuzumab to the doublet in the first-line setting . As a result of the CLEOPATRA trial, pertuzumab + trastuzumab + docetaxel was approved as the standard of care for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease .

    In a more recent analysis after a median follow-up of 99.9 months, the 8-year landmark OS rates were 37% with the addition of pertuzumab and 23% in the doublet group, demonstrating a long-term survival benefit after first-line treatment with the addition of pertuzumab . Moreover, the 8-year landmark PFS rates were 16% with the addition of pertuzumab and 10% in the doublet group, suggesting that a subgroup of patients might be cured after first-line treatment. Patients who present with de novo metastatic disease, not previously exposed to HER2-targeting agents, are more likely to experience long-term disease control, particularly with oligometastatic disease . PFS and OS estimates are strikingly good for these patients if they can achieve a no-evidence-of-disease status.

    Treatment Of Locally Advanced Or Inflammatory Breast Cancer

    In This Section
    • Fungating/painful breast or chest wall lesions.
    • After surgery for decompression ofintracranial or spinal cord metastases.
    • After fixation of pathologicfractures.

    Strontium chloride Sr 89, a systemically administered radionuclide, can beadministered for palliation of diffuse bony metastases.

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    Starting With Neoadjuvant Therapy

    Most often, these cancers are treated with neoadjuvant chemotherapy. For HER2-positive tumors, the targeted drug trastuzumab is given as well, often along with pertuzumab . This may shrink the tumor enough for a woman to have breast-conserving surgery . If the tumor doesnt shrink enough, a mastectomy is done. Nearby lymph nodes will also need to be checked. A sentinel lymph node biopsy is often not an option for stage III cancers, so an axillary lymph node dissection is usually done.

    Often, radiation therapy is needed after surgery. If breast reconstruction is planned, it is usually delayed until after radiation therapy is done. For some, additional chemo is given after surgery as well.

    After surgery, some women with HER2-positive cancers will be treated with trastuzumab for up to a year. Many women with HER2-positive cancers will be treated first with trastuzumab followed by surgery and then more trastuzumab for up to a year. If after neoadjuvant therapy, any residual cancer is found at the time of surgery, ado-trastuzumab emtansine may be used instead of trastuzumab. It is given every 3 weeks for 14 doses. For women with hormone receptor-positive cancer that is in the lymph nodes, who have completed a year of trastuzumab, the doctor might also recommend additional treatment with an oral targeted drug called neratinib for a year.

    Whats The Difference Between Her2

    Use of HER2-Targeted Therapy in Breast Cancer

    HER2 proteins can indicate whether breast cancer cells are likely to divide and replicate. HER2-negative breast cancer is more common and means that cancer cells are not producing a lot of HER2.

    HER2-positive breast cancer, on the other hand, means that the cells are producing a large number of these hormone receptors, indicating a more aggressive cancer.

    • having a history of receiving radiation therapy in your chest area
    • smoking or using other tobacco products

    Also, while having a family history of breast cancer generally increases your personal risk of breast cancer development, HER2-positive breast cancer is not hereditary.

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    Breast Cancer Clinical Practice Guidelines Consensus Documents And Position Statements

    Over time, some areas of breast cancer management may go through a phase of rapid change, whilst others may remain relatively constant over that time. Changes may occur as a result of the introduction of newer drugs or operative techniques. Most significant changes in practice come about following randomised trial evidence demonstrating efficacy.

    From the maximum tolerable to the minimum effective treatment, it is essential to escalate treatment when necessary, and to de-escalate when unnecessary. The most significant changes in breast cancer surgery and radiation oncology in the recent past involve de-escalation, the aim of which is to protect patients as much as possible from unnecessary morbidities of treatment, and to make treatment more tolerable.

    For example, instead of the previous 25 or 30 fractions of postoperative radiation after surgery for early breast cancer, which was administered over 5-6 weeks, it is now fairly standard that hypofractionated radiation courses are recommended in most cases, which usually involve 16 fractions over around 3 weeks, which proves much more convenient for patients.

    Treating Stage Iv Inflammatory Breast Cancer

    Patients with metastatic IBC are treated with systemic therapy. This may include:

    • Hormonal therapy
    • Targeted therapy with a drug that targets HER2
    • Immunotherapy if the cancer makes a protein called PD-L1
    • Targeted drug therapy with a PARP inhibitor called olaparib if the woman has a BRCA mutation

    One or more of these treatments might be used. Many times, a targeted drug is given along with chemotherapy or with hormone therapy. Surgery and radiation may also be options in certain situations. See Treatment of Stage IV Breast Cancer for more information.

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    Questions To Ask Your Doctor About Her2

    • What are my treatment options?
    • What is the best course of treatment for my cancer, and why?
    • Whats the overall goal of treatment in my case?
    • When should I start treatment?
    • Can I still work and manage my regular activities during this time?
    • How often will I be coming in to see you for treatment?
    • Will I be coming here for all my visits and treatments, or going elsewhere?
    • What short-term side effects and long-term risks are associated with my treatment?
    • What are the next steps if the desired treatment doesnt work?
    • How likely is it for my cancer to come back in the future? What symptoms should I be aware of?
    • What is the cost of my treatment?
    • What should I discuss with my insurance company?

    Physical Emotional And Social Effects Of Cancer

    Efficacy and safety of palbociclib in combination with letrozole as ...

    In general, cancer and its treatment cause physical symptoms and side effects, as well as emotional, social, and financial effects. Managing all of these effects is called palliative care or supportive care. It is an important part of your care that is included along with treatments intended to slow, stop, or eliminate the cancer.

    Supportive care focuses on improving how you feel during treatment by managing symptoms and supporting patients and their families with other, non-medical needs. Any person, regardless of age or type and stage of cancer, may receive this type of care. And it often works best when it is started right after a cancer diagnosis. People who receive supportive care along with treatment for the cancer often have less severe symptoms, better quality of life, and report that they are more satisfied with treatment.

    Supportive care treatments vary widely and often include medication, nutritional changes, relaxation techniques, emotional and spiritual support, and other therapies.

    • Music therapy, meditation, stress management, and yoga for reducing anxiety and stress.

    • Meditation, relaxation, yoga, massage, and music therapy for depression and to improve other mood problems.

    • Meditation and yoga to improve general quality of life.

    • Acupressure and acupuncture to help with nausea and vomiting from chemotherapy.

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    Targeted Drug Therapy For Breast Cancer

    Targeted drug therapy uses medicines that are directed at proteins on breast cancer cells that help them grow, spread, and live longer. Targeted drugs work to destroy cancer cells or slow down their growth. They have side effects different from chemotherapy and can be given in the vein , as an injection under the skin, or as a pill.

    Some targeted therapy drugs, for example, monoclonal antibodies, work in more than one way to control cancer cells and may also be considered immunotherapy because they boost the immune system.

    Like chemotherapy, these drugs enter the bloodstream and reach almost all areas of the body, which makes them useful against cancers that have spread to distant parts of the body. Targeted drugs sometimes work even when chemo drugs do not. Some targeted drugs can help other types of treatment work better.

    Several types of targeted therapy drugs can be used to treat breast cancer.

    Side Effects Of Her2 Targeted Drug Therapy

    The side effects of HER2 targeted drugs are often mild, but some can be serious. Discuss what you can expect with your doctor. If you are pregnant, you should not take these drugs. They can harm and even cause death to the fetus. If you could become pregnant, talk to your doctor about using effective birth control while taking these drugs.

    Monoclonal antibodies and antibody-drug conjugates can sometimes cause heart damage during or after treatment. This can lead to congestive heart failure. For most women, this effect lasts a short time and gets better when the drug is stopped. The risk of heart problems is higher when these drugs are given with certain chemo drugs that also can cause heart damage, such as doxorubicin and epirubicin . Other factors that can increase your risk of heart problems are being older than 50, being overweight or obese, having heart problems, and taking medicines for high blood pressure.

    Because these drugs can cause heart damage, doctors often check your heart function before treatment, and regularly while you are taking the drug. Let your doctor know if you develop symptoms such as shortness of breath, a fast heartbeat, leg swelling, and severe fatigue.

    Lapatinib, neratinib, tucatinib, and the combination of pertuzumab with trastuzumab can cause severe diarrhea, so its very important to let your health care team know about any changes in bowel habits as soon as they happen.

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    Explaining Differences Between Two Her2

    Several differences between T-DXd and T-DM1 could explain why T-DXd is more effective, Dr. Cortés said.

    The two drugs carry different types of chemotherapy payloads, and each molecule of T-DXd delivers about twice as much chemotherapy to HER2-positive cells as a molecule of T-DM1 does, Dr. Cortés explained.

    Perhaps most important, studies in mice and lab-grown cells indicate that once the chemotherapy component of T-DXd has been released, it can enter and kill neighboring cells, including tumor cells that do not overproduce HER2.

    In HER2-positive breast cancer, not all cells within a tumor overproduce HER2, Dr. Modi explained. So this bystander effect of T-DXd, which has not been seen with T-DM1, is particularly important for treating this form of breast cancer, she said.

    Treatment Of Breast Cancer Stages I

    Current Treatment Options for Patients With HER2-Positive Metastatic Breast Cancer

    The stage of your breast cancer is an important factor in making decisions about your treatment.

    Most women with breast cancer in stages I, II, or III are treated with surgery, often followed by radiation therapy. Many women also get some kind of systemic drug therapy . In general, the more the breast cancer has spread, the more treatment you will likely need. But your treatment options are affected by your personal preferences and other information about your breast cancer, such as:

    • If the cancer cells have hormone receptors. That is, if the cancer is estrogen receptor -positive or progesterone receptor -positive.
    • If the cancer cells have large amounts of the HER2 protein
    • How fast the cancer is growing
    • Your overall health
    • If you have gone through menopause or not

    Talk with your doctor about how these factors can affect your treatment options.

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    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 .

    Ajcc Anatomic And Prognostic Stage Groups

    There are three stage group tables for invasive cancer:

    • Anatomic Stage Group. The Anatomic Stage Group table is used in regions of the world where tumor grading and/or biomarker testing for ER, PR, and HER2 are not routinely available.
    • Clinical Prognostic Stage Group. The Clinical Prognostic Stage Group table is used for all patients in the United States. Patients who have neoadjuvant therapy as their initial treatment should have the clinical prognostic stage and the observed degree of response to treatment recorded, but these patients are not assigned a pathological prognostic stage.
    • Pathological Prognostic Stage Group. The Pathological Prognostic Stage Group table is used for all patients in the United States who have surgery as initial treatment and have pathological T and N information reported.

    In the United States, cancer registries and clinicians must use the Clinical and Pathological Prognostic Stage Group tables for reporting. It is expected that testing is performed for grade, HER2, ER, and PR status and that results are reported for all cases of invasive cancer in the United States.

    AJCC Anatomic Stage Groups

    AJCC Prognostic Stage Groups

    The Clinical Prognostic Stage is used for clinical classification and staging of patients in the United States with invasive breast cancer. It uses TNM information based on the patients history, physical examination, imaging results , and biopsies.

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