II. Management

  1. Stage 0: Lobular Carcinoma in-situ
    1. No treatment needed (biopsied lesion will not progress as it is not a malignancy)
    2. Increased risk of subsequent Breast Cancer development
      1. Consider Tamoxifen for prophylaxis
  2. Stage 0: Ductal Carcinoma in-situ (DCIS)
    1. Surgery
      1. Breast-Conserving Surgery with lumpectomy (2 mm clear margins) and Breast radiation OR
      2. Mastectomy (if extensive involvment or multifocal involvement) and Sentinel Node biopsy
    2. Five years of Hormonal Manipulation if Hormone Receptor Positive
  3. Stage 1 and 2: Early Invasive Breast Cancer
    1. Surgery
      1. Breast-Conserving Surgery with Sentinel Node biopsy and Breast radiation OR
      2. Mastectomy (for larger tumors) with Sentinel Node biopsy (and radiation if positive nodes)
    2. Hormone therapy if Hormone-receptor positive
    3. Immunotherapy
      1. Trastuzumab (Herceptin) if ERBB2 (HER2) overexpression
      2. Pertuzumab or Neratinib may be considered in certain tumor types
    4. Chemotherapy (except in tumor <1 cm and node negative)
      1. Guided by molecular testing (e.g. Oncotype DX)
      2. Especially important in triple negative Breast Cancer
      3. Agents
        1. Taxanes (low risk disease)
        2. Anthracyclines (high risk disease, triple negative, node positive)
        3. Capecitabine (triple negative, node positive disease)
  4. Stage 3: Locally Advanced Breast Cancer
    1. Induction Chemotherapy (triple negative) or Immunotherapy (ERBB2, ERP) that precedes resection
    2. Surgery
      1. Breast-Conserving Surgery with Breast radiation and Sentinel Lymph Node biopsy OR
      2. Mastectomy (for larger tumors) and Sentinel Lymph Node (SLN) biopsy
        1. Breast radiation if high risk, node-positive disease
      3. Axillary Lymph Node sampling indications
        1. Positive SLN Biopsy and Mastectomy
        2. Inflammatory Breast Cancer
        3. Positive nodes after preoperative Chemotherapy
    3. Hormone therapy if hormone-receptor positive
    4. Immunotherapy
      1. Trastuzumab (Herceptin) if ERBB2 (HER2) overexpression
      2. Pertuzumab or Neratinib may be considered in certain tumor types
    5. Chemotherapy (except in tumor <1 cm and node negative)
      1. Guided by molecular testing (e.g. Oncotype DX)
      2. Especially important in triple negative Breast Cancer
      3. Agents
        1. Taxanes (low risk disease)
        2. Anthracyclines (high risk disease, triple negative, node positive)
        3. Capecitabine (triple negative, node positive disease)
  5. Stage 4: Metastatic Breast Cancer
    1. Median survival 24 to 40 months
    2. Per patient wishes
    3. Consider palliative Radiation Therapy for pain
    4. Consider Bisphosphonates or donosumab for bone pain
    5. Consider Chemotherapy
    6. Hormone therapy if Estrogen-receptor positive
    7. Trastuzumab (Herceptin) if ERBB2 overexpression
  6. Recurrent Breast Cancer - Local involvement after Breast-Conserving Surgery
    1. Mastectomy
    2. Axillary Lymph Node sampling
    3. Chemotherapy
    4. Hormone therapy if Estrogen-receptor positive
    5. Trastuzumab (Herceptin) if ERBB2 overexpression
  7. Recurrent Breast Cancer - Local involvement after Mastectomy (typically involves chest wall)
    1. Wide excision
    2. Axillary Lymph Node sampling
  8. Recurrent Breast Cancer - Regional Involvement (axillary Lymph Node positive)
    1. Surgical resection
      1. Avoided if supraclavicular node or internal mammary node involvement
    2. Radiation Therapy
  9. Recurrent Breast Cancer - Distant Metastases (Stage 4 Breast Cancer)
    1. Endocrine therapy (if hormone receptor positive)
    2. ERBB2 (HER2) directed Immunotherapy if positive
    3. Chemotherapy as directed by biomarkers (e.g. Oncotype DX)

III. Management: Surgical

IV. Management: Chemotherapy

  1. Indications
    1. Most beneficial
      1. Lymph Node involvement
      2. Primary Breast Cancer larger than 1 cm
      3. Hormone receptor negative Breast Cancer
    2. Questionable benefit
      1. Age over 70 years
      2. Small, node-negative Breast Cancers (<1 cm)
      3. Favorable histologic subtypes
        1. Tubular cancers
        2. Mucinous cancers
  2. Anthracyclines
    1. Doxorubicin (Adriamycin) IV q14-21 days for 4-6 cycles
      1. Combined with Taxane (Docetaxel or Paclitaxel), and cyclophosphamide and/or fluorouracil
    2. Epirubicin (Ellence) every 21-28 days for 3-8 cycles
      1. Combined with cyclophosphamide or fluorouracil
  3. Taxanes
    1. Docetaxel IV every 21 days for 3-4 cycles
      1. Combined with anthracycline (doxorubicin or epirubicin), and cyclophosphamide and/or fluorouracil
    2. Paclitaxel IV every 7-21 days for 4-12 cycles
      1. Combined with doxorubicin and cyclophosphamide

V. Management: Hormonal Manipulation (Estrogen inhibition)

  1. Indications: Suppress Estrogen synthesis
    1. Hormone receptor positive
    2. Progesterone receptor positive (possible benefit)
    3. Hormone receptor indeterminate
  2. Protocol: Pre-Menopause
    1. Tamoxifen
      1. Selective Estrogen Receptor Modulator (SERM)
      2. Tamoxifen 20 mg orally daily (generic)
      3. Usually taken for first 5 years after diagnosis (2 years in some cases)
      4. May be followed by Aromatase inhibitor
      5. Adverse effects
        1. Venous Thromboembolism (NNH 200)
        2. Endometrial Cancer (NNH 250)
        3. Cataracts (NNH 38)
      6. Efficacy
        1. Reduces risk of cancer recurrence by 47%
        2. NNT 142 to prevent 1 case of invasive Breast Cancer after taking for 5 years
    2. Gonadotropin-releasing Hormone Agonist (LHRF agonist)
      1. Agent: Goserelin (Zoladex) SQ q1-3 months for 2 years
  3. Protocol: Post-Menopause
    1. Raloxifene
      1. Selective Estrogen Receptor Modulator (SERM)
      2. Raloxifene 60 mg orally daily
      3. Efficacy
        1. NNT 111 to prevent 1 case of invasive Breast Cancer after taking for 5 years
      4. Adverse Effects
        1. Venous Thromboembolism Risk (as with Tamoxifen)
        2. Lowers Osteoporosis risk and does not increase risk of Endometrial Cancer
    2. Aromatase inhibitor
      1. Agents (typically taken for 5 years, may be as short as 2 years in some cases)
        1. Anastrozole (Arimidex) 1 mg orally daily (generic)
        2. Letrozole (Femara) one tablet daily
        3. Exemestane (Aromasin) 25 mg orally daily
      2. Efficacy
        1. NNT 63 to prevent 1 case of invasive Breast Cancer after taking for 5 years
      3. Adverse Effects
        1. Osteoporosis (decreases Bone Mineral Density)
        2. Possible increased cardiovascular disease risk including CVA risk
      4. Consider as sequential treatment with aromatase inhibitor after Tamoxifen discontinued
      5. Osteoporosis risk (see Osteoporosis Prevention)
      6. Avoid in premenopausal women
        1. Osteoporosis risk
        2. Risk of Ovulation stimulation and higher risk of pregnancy
        3. Not as effective as in postmenopausal women

VI. Management: Biologics

  1. Trastuzumab (Herceptin)
    1. Monoclonal Antibody improves survival for overexpressors of ERBB2 (previously HER2 gene)
    2. Herceptin IV given with first dose of Chemotherapy and then every 1-3 weeks for 1 year
    3. Indicated for Her-2_neu positive, ERBB2 overexpressing patients with metastatic Breast Cancer
  2. Pertuzumab (Perjeta)
    1. Monoclonal Antibody
  3. Neratinib (Nerlynx)
    1. Oral Tyrosine Kinase inhibitor
  4. References
    1. Slamon (2001) N Engl J Med 344:783-92 [PubMed]
    2. Smith (2007) Lancet 369:29-36 [PubMed]

VII. Resources

  1. Adjuvant! for Breast Cancer
    1. http://www.adjuvantonline.com
    2. Predicts prognosis and allows comparison of various adjuvant interventions in terms of outcome

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