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Learn Metastatic Breast Cancer PowerPoint Presentation

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  • Slide 1 - Metastatic Breast Cancer Jennifer Low, MD, PhD November 17, 2003
  • Slide 2 - BREAST CANCERStage IV Any T any N M1 Examples of distant mestastatic disease
  • Slide 3 - BREAST CANCERSites of distant metastases Skin Liver Bone Pleura Lung Lymph nodes Brain
  • Slide 4 - BREAST CANCERLiver metastasis
  • Slide 5 - Survival from Metastatic BC From Greenberg P (MDAnderson), JCO 14: 2197, 1996
  • Slide 6 - Modalities of treatment Surgery may be considered for isolated local and regional recurrences, possibly for some isolated metastases Radiation for “impending catastrophe” (spinal cord compression, superior vena cava syndrome, impending fracture, palliation, brain metastases) or inoperable local/regional disease Systemic therapy for disseminated disease, disease not falling into above categories
  • Slide 7 - Targeted Therapy in Breast Cancer Hormone receptor status Any Estrogen Receptor (ER) or Progesterone Receptor (PR) expression indicates possible response to hormonal therapy 1% or more cells positive or ER or PR by immunohistochemistry Her2/neu (ErbB-2) overexpression High overexpression of Her2/neu indicates possible responder to trastuzumab therapy ER/PR/Her2 negative patients: chemotherapy
  • Slide 8 - Metastatic Breast Cancer Generally considered incurable For most patients, primary goal should be palliation First recurrences are always biopsied to confirm diagnosis Confirm ER/PR status and Her2/neu status
  • Slide 9 - Metastatic disease: Systemic therapy principles Hormonal therapy for indolent disease Single agent chemotherapy for aggressive/symptomatic disease or disease not responsive to hormonal therapy Polyagent chemotherapy for visceral crisis or disease requiring rapid response
  • Slide 10 - Systemic Treatment Approach for Metastatic Breast Cancer Metastatic Breast Cancer Limited metastases (bone & soft tissue) Positive hormone receptors Hormone responsive Disease-free interval 2 years Extensive metastases or visceral crisis Negative hormone receptors No response to hormones Hormonal Therapy Chemotherapy Response No response No progression Progression of disease If disease progresses, second-line hormonal therapy Second-line chemotherapy
  • Slide 11 - Rationale for Hormonal Treatmentof Breast Cancer Endocrine manipulation can: Decrease levels of estrogen thatstimulate tumor growth Block estrogen interaction with estrogen receptors Less toxicity Response rates in metastatic disease: 30% of unselected patients 50% of ER-positive patients
  • Slide 12 - Hormonal Therapies (FDA indications) 1st line therapy: Tamoxifen, anastrozole (Arimidex), letrozole (Femara) 2nd line therapy: Fulvestrant (Faslodex), toremifene (Fareston), exemestane (Aromasin) “Palliative” Goserelin (LHRH analog, Zoladex)
  • Slide 13 - Hormonal Therapies for Post-menopausal Metastatic Tamoxifen 20 mg po daily Aromatase inhibitors: anastrozole 1 mg po daily, letrozole 2.5 mg po daily exemestane 25 mg po daily Fulvestrant 250 mg IM q month Megace 40 mg po QID Aminoglutethimide 250 mg po QID with hydrocortisone
  • Slide 14 - Hormonal therapy for Premenopausal Metastatic LHRH analog 7.5 mg depot every 28 days Tamoxifen 20 mg po daily May be considered with LHRH analog: anastrozole 1 mg po daily, letrozole 2.5 mg po daily exemestane 25 mg po daily Fulvestrant 250 mg IM q month ?? Premenopausal dose may be higher? Megace 40 mg po QID
  • Slide 15 - Treatment Sequence for Postmenopausal Women With Metastatic Breast Cancer First line Second line Third line Fourth line Chemotherapy Antiestrogen or Nonsteroidal Aromatase Inhibitor (AI) Nonsteroidal AI or Antiestrogen Steroidal AI Progestin Fifth line Androgen if response if response if response NoResponse
  • Slide 16 - Treatment of Metastatic Breast Cancer: Cytotoxic Agents Anthracyclines (doxorubicin, liposomal doxorubicin) Cyclophosphamide Taxanes (paclitaxel, docetaxel) Antimetabolites (5-FU, capecitabine) Gemcitabine Vinorelbine Carboplatin/cisplatin
  • Slide 17 - Her2/neu status Membrane-associated tyrosine kinase receptor (aka erbB2) related to EGF Expressed in breast cancers, DCIS, and some other tissues such as heart Overexpressed in 25-30% of breast cancers Associated with more aggressive disease and worse prognosis
  • Slide 18 - Measurement of Her2/neu Measured by immunohistochemistry (IHC) Graded 0, 1+, 2+, or 3+ Based on characteristics of staining 0-1 = negative 2 = indeterminant, should be followed with FISH (fluorescent in situ hybridization) to determine status (amplified/not amplified) 3 = positive Fluorescence In Situ Hybridization (FISH) correlates with response to Herceptin, but more expensive than IHC
  • Slide 19 - Trastuzumab (Herceptin) Humanized monoclonal antibody against her2/neu FDA approved for metastatic breast cancer in 1998 Responses in patients with her2/neu positive breast cancer IHC 3+ FISH positive Single agent therapy has 26% response rate as 1st line therapy May be given as an IV infusion weekly or every 3 weeks
  • Slide 20 - Herceptin + Chemotherapy Response rate approx 25% as single agent, as high as 75% in combination therapy Taxol Taxotere Vinorelbine Gemcitabine Capecitabine Taxane/platinum
  • Slide 21 - High Dose Chemotherapy with Stem Cell Rescue Metastatic pts with CR/PR randomized to HD/ABMT vs conventional tx 33 vs 38% 3yr survival Stadtmauer EA, et al., NEJM 342:1069, 2000
  • Slide 22 - Pamidronate in Metastatic Cancer Biphosphonates inhibit osteoclast-induced bone resorption 380 randomized patients stage IV disease with at least 1 lytic bone lesion 195 patients: chemotherapy + placebo 185 patients: chemotherapy plus pamidronate (90 mg IV q month x 12) Hortobagyi GN et al, NEJM 335: 1785-1791, 1996
  • Slide 23 - Pamidronate decreases skeletal complications in breast cancer Hortobagyi GN et al, NEJM 335: 1785-1791, 1996 43% vs 56% had any skeletal complication after 12 months of therapy
  • Slide 24 - Zoledronic Acid (Zometa) Bisphosphonic acid – inhibitor of osteoclastic bone resorption Indicated for solid tumor patients with bone metastases 4 mg IV over 15-30 minutes Check serum creatinine before each administration Comparable in efficacy to pamidronate Rosen LS, Cancer J 7:377, 2001
  • Slide 25 - Metastatic disease: More thoughts on palliation Because metastatic breast cancer is not considered curable, there are very few imperatives of treatment regimens Clinical trials at any point of metastatic diagnosis is appropriate Treatment should be individualized to maximize the patient’s needs and life goals
  • Slide 26 - NCI Phase II Clinical Trials for Breast Cancer BMS-247550 Epothilone B analog Microtubule stabilizer Active in taxane resistant tumors Phase II trial Measurable disease Metastatic or locally advanced patients for whom you would consider taxane therapy Tamoxifen/Zarnestra Oral farnesyl transferase inhibitor, (inhibits ras oncogene pathway) May reverse tamoxifen resistance Phase II trial Measurable disease Hormone receptor positive T cell depleted allogeneic stem cell transplant Immunotherapy to induce a graft vs tumor effect Phase II trial Measurable disease HLA matched sibling donor Prior chemotherapy
  • Slide 27 - Metastatic Breast CancerCase Presentation Patient CC Jennifer Low, MD, PhD
  • Slide 28 - Case Presentation At age 30, found to have stage IIIA right breast cancer ER/PR positive, her2/neu negative Treated with neoadjuvant chemotherapy, then mastectomy with lymph node dissection and radiation and tamoxifen 1st recurrence at right chest wall during radiation therapy Treated with radiation 2nd recurrence to spine a few months later Treated with radiation, removal of ovaries
  • Slide 29 - Case Presentation, cont. 2 years after original diagnosis, she found Left (contralateral) breast mass (ER/PR positive, Her2/neu 3+) Lung metastasis Liver metastasis Treated with mastectomy, anastrazole (hormonal therapy) Several months later, developed pleural effusion Treated with Herceptin and Taxol
  • Slide 30 - Case Presentation, cont. After Herceptin + Taxol: NCI Clinical trial with docetaxel and flavopiridol (with progressive disease) NCI Clinical trial with BMS-247550 (epothilone analog) for 8 months with partial response Herceptin + Vinorelbine since July with stable disease
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