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BREAST CANCER - Coggle Diagram

- - - - MOA:
        
        inhibits estrogen binding to its receptor and the blocking of the proliferative actions of estrogen on mammary epithelium
        
        the induction by tamoxifen of the synthesis of the cytokine transforming growth factor-β (TGF-β)
        
        decrease the circulating levels of insulin-like growth factor 1 in breast cancer patient
      - Side Effects:
        
        Uterine malignancies, pulmonary embolism, and stroke in patients who are at high risk for cancer or who have ductal carcinoma in situ
        
        Menopausal symptoms (hot flushes, night sweats and sleep disturbance, vaginal irritation)
        
        Change of period
        
        Increase of blood clots
      - Drug that has same MOA and differences:
        Other drug that has same MOA as Tamoxifen is Raloxifene. Raloxifene act as anti estrogen in uterus thus, reduced the risk of endometrial cancer while Tamoxifen act as agonist estrogen in uterus hence, increase the risk of endometrial cancer. Raloxifene is 2nd generation of SERM so it has lower incidence of serious side effects.
    - - Side effects:
        • fever,
        • nausea,
        • vomiting,
        • infusion reactions,
        • diarrhoea,
        • cough,
        • headache,
        • fatigue,
        • shortness of breath,
        • rash,
        • reduced white cells and red blood cells number,
        • muscle pains
        • cardiotoxicity: congestive heart failure
        • pulmonary toxicity: pneumonia
      - MOA:
        Trastuzumab have 3 main mechanism of action.
        
        HER-2 degradation - Triggers HER2 internalization and degradation by promoting the activity of tyrosine kinase – ubiquitin ligase c-Cbl. c-Cbl ubiquitinates HER2 and leads to its degradation
        
        Antibody-dependent cellular cytotoxicity - Attracts immune cells to tumor sites that overexpress HER2
        
        MAPK and PI3K/Akt interference - Interferes with the dimerization of HER2, inhibiting the activation of HER2 and suppresses the downstream pathways leading to reduction in cell growth and survival. §
      - Other drugs that have same MOA as trastuzumab and the differences:
        
        Pertuzumab: binds to an epitope in domain II, the dimerization domain of the HER2 extracellular domain, which is distinct from the binding site of trastuzumab in domain IV.
        
        Trastuzumab and hyaluronidase injection: HERCEPTIN HYLECTA is for subcutaneous use only over approximately 2-5 minutes once every three weeks compared to 30 to 90 minutes for intravenous trastuzumab.
      - Combination therapy
        
        Anthracycline based regimen
        Combination of both agents also
        shows low cardiac toxicity with the
        same effectiveness as monotherapy.
        
        Pacitaxel
        -combination of both agents give no infusion reaction and no heart impairment to the patients.
- - - - Specificity
        
        Potent and highly selective inhibitors towards CDK-4 and CDK-6.
        
        non-toxic to normal cells and can avoid any unacceptable side effects.
      - Side Effect:
        Neutropenia, low white blood cell count, weakness, fatigue, anemia, upper respiratory infection, nausea, inflammation of the mouth and lips, mouth sores, hair thinning or loss, diarrhea, low platelet count, decreased appetite, vomiting, numbness or tingling in the hands and feet, nosebleed, blurred vision, dry or watery eyes, headache, changes in taste, constipation, rash, dry skin, or fever.
      - MOA
        Reduces cellular proliferation of estrogen-receptor-positive breast cancer cells by blocking progression of the cell from G1 into the S phase of the cell cycle.
        Selectively inhibits cyclin-dependent kinase 4 (CDK4) and 6 (CDK6). CDK4 and 6 are serine/threonine kinases that are upregulated in many tumor cell types and play a key role in the regulation of cell cycle progression.à Thereby inhibiting retinoblastoma (Rb) protein phosphorylation early in the G1 phase leading to cell cycle arrest. à This suppresses DNA replication and decreases tumor cell proliferation.
        Drugs that have same MOA:
        Ribociclib & Abemaciclib
    - - Surgery
        
        Commonly surgery is not a good choice for treatment especially when the cancer cell already spreads to other parts of the organ. However, surgery also can still be an option for certain conditions such as to prevent broken bones referring to Salmah problem.
      - Second line chemotherapy
        
        combination of monoclonal antibody therapy with chemotherapy. Based on a study, combination of bevacizumab with standard chemotherapy found to be safe and effective in treating metastatic breast cancer. The overall survival is 18 months (Yamamoto et.al, 2020).
      - Local treatment
        
        i) bone strengthening medication
        (denosumab,zoledronic acid)
        
        ii) radiation therapy (external beam radiation therapy,
        stereotactic body radiation therapy,
        radiopharmaceutical (strontium-89))
        
        iii) ablation (thermal ablation,
        radiofrequency ablation
        and cryoablation)
        
        iv) bone cement. (Vertebroplasty,
        kyphoplasty,
        cementoplasty)
    - - Other drugs have same MOA and differences :
        
        Exemestane as a steroidal analog and irreversibly bind to aromatase while anastrozole a non steroidal analog and bind reversibly to aromatase.
        
        Letrozole is a more potent and effective inhibition of aromatase enzyme compare to anastrozole.
      - Mechanism of action
        A potent and selective nonsteroidal aromatase inhibitor, inhibits aromatase enzyme by preventing the conversion of androstenedione to oestrone and testosterone to oestradiol, leading to decreased serum estradiol concentration, decreased tumour mass or delayed progression in patients with tumours responsive to hormones
    - - Side Effect:
        Injection site reactions (pain, swelling, redness), nausea, vomiting, loss of appetite, constipation, diarrhea, upset stomach, dizziness, headache, tiredness, weakness, headache, back pain, joint pain, muscle pain, pain in your arms or legs, other body aches/pains, flushing and sweating (hot flushes/hot flashes), tiredness, cough, trouble sleeping, or trouble breathing.
      - MOA
        Antiestrogenic effects (block action of estrogen on cancer cells - slow or stop the growth of breast tumors that need estrogen to grow)
        Binds to estrogen receptor monomers to inhibit receptor dimerization.
        Activating function 1 (AF1) and AF2 are rendered inactive.
        Reduces translocation of receptors to the nucleus.
        Accelerates the degradation of estrogen receptors.
        Other drugs that have same MOA:
        Brilanestrant & elacesttrant (Both have not approved by FDA yet)