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Targeted Therapy For Breast Cancer

Lapatinib: Blocking Abnormal Proteins That Signal Cancer Cells To Multiply

Mayo Clinic Minute: Using targeted therapy to treat breast cancer

This tablet, taken by mouth, helps stop or slow the spread of cancer cells. Lapatinib is given with chemotherapy or after other methods have not worked to slow the cancer.

Lapatinib is for HER2 positive breast cancers and is commonly used for metastatic breast cancer that has spread to the brain since it crosses the blood-brain barrier.

Side effects can include nausea, vomiting, diarrhea, tiredness, mouth sores, and rashes. It can also cause red, painful hands and feet. Before treatment, your doctor will check your heart and liver. During treatment, your doctor will watch for signs of heart, lung, or liver problems.

As with all medical treatments, if you experience unusual changes in your health during targeted therapy, notify your doctor immediately.

Tnbc And Parp Inhibitors

TNBC represent 10%-20% of invasive breast cancers in the general population and have been associated with the African-American ethnic group where a clear prevalence of the disease affects up to 28% of all patients within that group.

The main challenge of circumventing treatment induced resistance mechanisms and the emergence of alternative escape pathways, significantly lowers the overall survival rate of breast cancer patients belonging to this particular subtype as they often exhibit an incomplete pathological response.

Sunitinib seems to suppress angiogenesis, tumor proliferation, migration and growth of basal like breast cancer cells xenograft models indicate that tumor volumes decrease under sunitinib action but due to its effects on the Notch-1 protein expression and hypoxia through HIF-1, there was an increase in proliferation of breast cancer stem cells. The use of a -secretase inhibitor in addition to sunitinib may represent a promising treatment option for TNBC while simultaneously targeting cancer stem cells and angiogenesis.

Sunitinib may prove to be an effective treatment choice for patients with TNBC as this breast cancer subtype may express increased levels of VEGF. High levels of VEGF may act as a potential prognostic factor in TNBC as the vascular pathway is a key component when targeting this particularly rare subtype of breast cancer.

Ovarian Ablation Or Suppression

In women who have not yet experienced the menopause, oestrogen is produced by the ovaries.

Ovarian ablation or suppression stops the ovaries working and producing oestrogen.

Ablation can be done using surgery or radiotherapy. It permanently stops the ovaries from working and means you’ll experience the menopause early.

Ovarian suppression involves using a medicine called goserelin, which is a luteinising hormone-releasing hormone agonist .

Your periods will stop while you’re taking it, although they should start again once your treatment is complete.

If you’re approaching the menopause , your periods may not start again after you stop taking goserelin.

Goserelin comes as an injection you have once a month.

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Targeted Therapy For Men With Brca Mutations

Olaparib and talazoparib are drugs known as PARP inhibitors. PARP proteins normally help repair damaged DNA inside cells. The BRCA genes also help repair DNA , but mutations in one of those genes can stop this from happening. PARP inhibitors work by blocking the PARP proteins. Because tumor cells with a mutated BRCA gene already have trouble repairing damaged DNA, blocking the PARP proteins often leads to the death of these cells.

Olaparib and talazoparib can be used to treat metastatic, HER2-negative breast cancer in patients with a BRCA mutation who have already gotten chemotherapy .

Only a portion of men with breast cancer have a mutated BRCA gene that they are born with, and which is in all the cells of the body . If you are not known to have a BRCA mutation, your doctor will test your blood to be sure you have one before starting treatment with one of these drugs.

These drugs come in pills that are taken once or twice a day.

Side effects can include nausea, vomiting, diarrhea, fatigue, loss of appetite, taste changes, low red blood cell counts , low platelet counts, low white blood cell counts, belly pain, and muscle and joint pain. Rarely, some people treated with a PARP inhibitor have developed a blood cancer, such as myelodysplastic syndrome or acute myeloid leukemia .

Mechanisms Of Resistance To Current Her2

Targeted Therapy

Mechanisms of resistance to trastuzumab: epitope masking, such that a cell surface molecule hides the epitope to which trastuzumab binds, preventing recognition and binding of human epidermal growth factor receptor 2 by trastuzumab receptor cross talk, where cell surface receptor kinase such as insulin-like growth factor 1 receptor and Met stimulate activation of HER2 signaling increased expression and secretion of ligands that activate HER2 signaling, including growth differentiation factor 15 , transforming growth factor alpha, and heregulin increased phosphatidylinositol-3 kinase /mammalian target of rapamycin signaling reduced expression of G1 arrest mediator p27Kip1 , and increased expression of apoptotic inhibitors B-cell lymphoma 2 , myeloid cell leukemia sequence 1 , and survivin.

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Aconseguint Una Terpia Contra El Cncer Dirigida

Què és la teràpia dirigida?

Què distingeix el tractament dirigit de la quimioteràpia?

Els medicaments de teràpia dirigida, com altres teràpies contra el càncer, es classifiquen com a quimioteràpia. Els medicaments de tractament dirigit, en canvi, no són el mateix que els típics o quimioteràpia estàndard . Els medicaments dirigits tenen com a objectiu algunes de les diferències que distingeixen les cèl·lules canceroses de les normals. Això els distingeix de la quimioteràpia de dues maneres principals:

  • Aquests medicaments tenen un efecte sobre les cèl·lules canceroses, però normalment deixen les cèl·lules normals i sanes soles a causa de la seva activitat focalitzada. La quimioteràpia tradicional és citotòxica per a la majoria de les cèl·lules, el que significa que pot danyar les cèl·lules normals i sanes, així com les cèl·lules malignes.
  • Els medicaments dirigits sovint operen impedint que les cèl·lules canceroses es repliquin. D’aquesta manera, poden ajudar una cèl·lula cancerosa a deixar de dividir-se i produir noves cèl·lules canceroses. La quimioteràpia, en canvi, destrueix les cèl·lules canceroses que ja s’han format.
  • Com funciona la teràpia dirigida

    • Massa d’una determinada proteïna en una cèl·lula cancerosa
    • Una proteïna d’una cèl·lula cancerosa que no es troba a les cèl·lules normals
    • Una proteïna que es muta d’alguna manera en una cèl·lula cancerosa
    • Canvis genètics que no es troben en una cèl·lula normal.

    L’acció dels fàrmacs dirigits pot funcionar per:

    Who Gets Targeted Therapy

    Some types of cancer, like CML, almost always have a target that treatment can focus on. But sometimes, your doctor will need to test your tumor to see if it has any targets. Sometimes they’ll do a biopsy — take a small sample from the tumor and check it in a lab.

    Even if you have the same type of cancer as someone else, you might not have the same target. Not all breast cancers are HER2-positive. Targeted colon cancer medicines like cetuximab won’t work if you have the KRAS gene mutation.

    Before your doctor recommends a targeted therapy, you might have to try other treatments first. Targeted therapy is often given along with other treatments.

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    What Are Targeted Therapies

    Targeted therapies interfere with the way cancer cells grow.

    The main targeted therapy drug used in breast cancer treatment is trastuzumab. It reduces the risk of breast cancer coming back in women with HER2 positive breast cancer.

    It is also used in men with HER2 positive breast cancer.

    Trastuzumab may be given with chemotherapy, or on its own. This can be before or after surgery and radiotherapy.

    You may have trastuzumab in combination with another targeted therapy drug called pertuzumab and a chemotherapy drug. This combination may be used before surgery to treat HER2 positive breast cancer that has a high risk of coming back.

    Trastuzumab and pertuzumab attach to the HER2 receptors on the surface of breast cancer cells and stop them from dividing and growing.

    You usually have trastuzumab every 3 weeks for 1 year. It is given in the chemotherapy day unit or outpatient department.

    You have trastuzumab in one of the following ways:

    Targeted Therapy For Breast Cancer

    Targeted treatment for breast cancer – Mayo Clinic

    Targeted therapy is usually used to treat breast cancer. It uses drugs to target specific molecules on cancer cells or inside them. These molecules help send signals that tell cells to grow or divide. By targeting these molecules, the drugs stop the growth and spread of cancer cells and limit harm to normal cells. Targeted therapy may also be called molecular targeted therapy.

    You may have targeted therapy to:

    • stop breast cancer cells from growing and spreading
    • lower the risk that the cancer will come back
    • treat breast cancer that has spread to other parts of the body and that no longer responds to other breast cancer treatments

    Your healthcare team will consider your personal needs to plan the drugs, doses and schedules of targeted therapy. You may also receive other treatments.

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    What Is Targeted Therapy

    In addition to chemotherapy and hormone therapy, there are newer, more effective treatments that can attack specific breast cancer cells without harming normal cells. Currently, these targeted methods are commonly used in combination with traditional chemotherapy. However, targeted drugs often have less severe side effects than standard chemotherapy drugs.

    Side Effects Of Trastuzumab

    Your medical team will monitor you for side effects. These are usually caused by the chemotherapy. This means that once chemotherapy finishes and you are continuing with trastuzumab only, most side effects ease. For example, hair grows back, there is no nausea or vomiting, and you no longer need regular blood tests.

    Although side effects from trastuzumab itself are uncommon, they can include headache, fever and diarrhoea. In some people, trastuzumab can affect how the heart works, so you will have tests to check your heart function before and during treatment.

    Several new drugs have been developed as additional treatments after trastuzumab for people with HER2+ breast cancer, including pertuzumab and trastuzumab emtansine . Your doctor will advise if these are appropriate for you.

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    Recent Development Of Targeted Approaches For The Treatment Of Breast Cancer

    New approaches for improving outcomes in breast cancer in Europe
    Angelo Di Leo et al. BREAST
    Investigation of -3-acrylic Acids as Oral Selective Estrogen Receptor Down-Regulators
    Sébastien L. Degorce et al. JOURNAL OF MEDICINAL CHEMISTRY
    Oral Selective Estrogen Receptor Downregulators , a Breakthrough Endocrine Therapy for Breast Cancer
    Donald P. McDonnell et al. JOURNAL OF MEDICINAL CHEMISTRY
    Pembrolizumab
    Leila Khoja et al. Journal for ImmunoTherapy of Cancer
    Inhibition of proliferation and migration of luminal and claudin-low breast cancer cells by PDGFR inhibitors
    Leanne Stalker et al. Cancer Cell International
    First FDA Approval of Neoadjuvant Therapy for Breast Cancer: Pertuzumab for the Treatment of Patients with HER2-Positive Breast Cancer
    L. Amiri-Kordestani et al. CLINICAL CANCER RESEARCH
    Phase I/II Trial of Vinorelbine and Sorafenib in Metastatic Breast Cancer
    Thehang Luu et al. Clinical Breast Cancer
    Mounting Evidence for Prediagnostic Use of Statins in Reducing Risk of Lethal Prostate Cancer
    Lorelei A. Mucci et al. JOURNAL OF CLINICAL ONCOLOGY
    Ganitumab with either exemestane or fulvestrant for postmenopausal women with advanced, hormone-receptor-positive breast cancer: a randomised, controlled, double-blind, phase 2 trial
    John FR Robertson et al. LANCET ONCOLOGY
    Hedgehog Signaling Is a Novel Therapeutic Target in Tamoxifen-Resistant Breast Cancer Aberrantly Activated by PI3K/AKT Pathway
    B. Ramaswamy et al. CANCER RESEARCH

    Synergy With Lapatinib And Trastuzumab

    Figure 2 from Targeted therapy for breast cancer.

    With newer HER2 drugs in the pipeline, researchers investigated the effects of using lapatinib and trastuzumab together. It has been found that lapatinib could enhance trastuzumab by increasing the apoptotic effect . Blackwell et al. presented results of the Phase III EGF104900 trial, which demonstrated that lapatinib plus trastuzumab significantly improved progression-free survival and clinical benefit rate versus lapatinib monotherapy . A total of 291 randomly assigned HER2 positive metastatic breast cancer patients whose disease that progress during prior trastuzumab therapy were assigned to receive lapatinib monotherapy or a combination of lapatinib and trastuzumab . The study concluded that absolute overall survival rates were 10% at 6 months and 15% at 12 months in the combination arm compared with the monotherapy arm demonstrating a significant 4.5-month median OS advantage with lapatinib and trastuzumab combination in support dual HER2 blockade in patients previously treated HER2 positive metastatic breast cancer .

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    How Are Herceptin And Other Biologic Targeted Therapies Administered And What Are The Likely Side Effects

    The drug Herceptin is given through a vein. It may be given alone or with chemotherapy. Side effects that most commonly occur during the first treatment include fever and chills.

    Other possible side effects include weakness, nausea, vomiting, diarrhea, headaches, difficulty breathing, and rashes. These side effects generally become less severe after the first treatment. Herceptin also may cause heart damage, heart failure, and serious breathing problems. Before and during treatment, your doctor will check your heart and lungs.

    Targeted Therapy In Breast Cancer

    Due to an increased knowledge on how to run well-designed clinical trials, development of cancer drugs has evolved substantially, including cytotoxic agents, endocrine agents and new-generation targeted drugs. However, the major aims are still to register and establish new drugs for broad groups of rather unselected patients based on crude conventional classification systems. As in general only a small group of patients experiences an advantage, current trials must have large sample sizes to be able to detect small efficacy differences. Despite this, significant achievements have been made for breast cancer with the use of new drugs in the metastatic and the adjuvant setting . These improvements, however, have been paid for by overtreatment and undertreatment of large cohorts of patients.

    Currently targeted drug selection in breast cancer is exclusively based on estrogen receptor , progesterone receptor and human epidermal growth factor receptor expression mainly of the primary tumor, even if metastatic disease is actually treated. Retrospective data indicate discordance regarding those factors between primary tumors and corresponding metastatic lesions in up to 44% of patients, which would even require alterations during palliative treatment . For better patient selection this indicates the need for prospective target evaluation not only in the primary tumor but also in metastatic lesions.

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    Targeted Therapy Side Effects

    There are many types of targeted therapy. The potential side effects of targeted therapy depend on which targeted therapy drug you are given and the drug targets. Some targeted therapy has minimal side effects whilst others may lead to uncommon but serious problems. Side effects also vary from one person to another.

    Side effects of targeted therapies may include:

    • sensitivity to sunlight your skin may become dry, red, or itchy
    • skin rash that looks like acne
    • tenderness and rash of the palms of the hands and soles of the feet
    • muscle, bone, and joint pain
    • high blood pressure
    • bleeding or blood clots
    • slow wound healing
    • changes to the way the heart works

    Some targeted therapies may have unique side effects not covered in the list above. Your doctors will advise and monitor you for these side effects.

    It is important to note that not every person will experience every side effect and the type and severity of these side effects vary from patient to patient. Most of these side effects can be managed with supportive measures. In some cases, your doctor may reduce the dosage of your medications. Please monitor your condition and notify your cancer care team if unexpected side effects occur.

    When Is Targeted Therapy Given

    Targeted Therapy in Advanced Breast Cancer

    Some people have targeted therapy after surgery to reduce the chances of their breast cancer coming back.

    Sometimes targeted therapy is given before surgery to shrink a larger cancer before its removed.

    Targeted therapies can also be given if breast cancer has come back or spread to another part of the body.

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    Safety Of Targeted Therapy

    You need to take certain precautions when receiving targeted therapy. This is to protect your family and friends from unnecessary exposure to cancer drugs.

    If you are given oral targeted therapy to take at home, you should not let your family members or friends come into contact with the medication. Sometimes this may also include contact with your body fluids while you undergo treatment .

    Are There Limitations To Targeted Therapy

    As with any cancer treatment, targeted therapy may not be the best treatment for every person with cancer. It may seem simple to use a drug for your specific cancer, but targeted therapy is complex, and it may not be the right drug for you. It is important to know that:

    • A targeted treatment will not work if the tumor does not have the specific genetic change or protein the drug targets

    • Even if you have the specific genetic change or protein the drug targets, it’s possible the tumor will not respond to the drug

    • The response to the treatment may not last over time

    For example, the target may not be as important for the cancer’s growth as previously thought, so the drug does not provide much benefit. Or cells may become resistant to targeted therapy, so the drug may work at first but then stop working over time. If this happens, the doctor will talk with you about other treatment options.

    Like many cancer treatments, targeted therapy drugs can cause serious side effects. These are usually not the same as chemotherapy side effects, because these two categories of drugs work differently. For example, people who get targeted therapy are more likely to have skin, hair, nail, or eye problems. It is always important to talk to your doctor about each drug prescribed for you, including the specific side effects to watch for and how they can be managed.

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