II. Management
- Stage 0: Lobular Carcinoma in-situ
- No treatment needed (biopsied lesion will not progress as it is not a malignancy)
- Increased risk of subsequent Breast Cancer development
- Consider Tamoxifen for prophylaxis
- Stage 0: Ductal Carcinoma in-situ (DCIS)
- Surgery
- Breast-Conserving Surgery with lumpectomy (2 mm clear margins) and Breast radiation OR
- Mastectomy (if extensive involvment or multifocal involvement) and Sentinel Node biopsy
- Five years of Hormonal Manipulation if Hormone Receptor Positive
- Surgery
- Stage 1 and 2: Early Invasive Breast Cancer
- Surgery
- Breast-Conserving Surgery with Sentinel Node biopsy and Breast radiation OR
- Mastectomy (for larger tumors) with Sentinel Node biopsy (and radiation if positive nodes)
- Hormone therapy if Hormone-receptor positive
- Immunotherapy
- Trastuzumab (Herceptin) if ERBB2 (HER2) overexpression
- Pertuzumab or Neratinib may be considered in certain tumor types
- Chemotherapy (except in tumor <1 cm and node negative)
- Guided by molecular testing (e.g. Oncotype DX)
- Especially important in triple negative Breast Cancer
- Agents
- Taxanes (low risk disease)
- Anthracyclines (high risk disease, triple negative, node positive)
- Capecitabine (triple negative, node positive disease)
- Surgery
- Stage 3: Locally Advanced Breast Cancer
- Induction Chemotherapy (triple negative) or Immunotherapy (ERBB2, ERP) that precedes resection
- Surgery
- Breast-Conserving Surgery with Breast radiation and Sentinel Lymph Node biopsy OR
- Mastectomy (for larger tumors) and Sentinel Lymph Node (SLN) biopsy
- Breast radiation if high risk, node-positive disease
- Axillary Lymph Node sampling indications
- Positive SLN Biopsy and Mastectomy
- Inflammatory Breast Cancer
- Positive nodes after preoperative Chemotherapy
- Hormone therapy if Hormone-receptor positive
- Immunotherapy
- Trastuzumab (Herceptin) if ERBB2 (HER2) overexpression
- Pertuzumab or Neratinib may be considered in certain tumor types
- Chemotherapy (except in tumor <1 cm and node negative)
- Guided by molecular testing (e.g. Oncotype DX)
- Especially important in triple negative Breast Cancer
- Agents
- Taxanes (low risk disease)
- Anthracyclines (high risk disease, triple negative, node positive)
- Capecitabine (triple negative, node positive disease)
- Stage 4: Metastatic Breast Cancer
- Median survival 24 to 40 months
- Per patient wishes
- Consider palliative Radiation Therapy for pain
- Consider management for bone metastases to reduce Fracture risk and Hypercalcemia
- Bisphosphonates (e.g. Zoledronic Acid, Pamidronate)
- Donosumab (Prolia)
- Consider Chemotherapy
- Hormone therapy if Estrogen-receptor positive
- Trastuzumab (Herceptin) if ERBB2 overexpression
- Recurrent Breast Cancer - Local involvement after Breast-Conserving Surgery
- Mastectomy
- Axillary Lymph Node sampling
- Chemotherapy
- Hormone therapy if Estrogen-receptor positive
- Trastuzumab (Herceptin) if ERBB2 overexpression
- Recurrent Breast Cancer - Local involvement after Mastectomy (typically involves chest wall)
- Wide excision
- Axillary Lymph Node sampling
- Recurrent Breast Cancer - Regional Involvement (axillary Lymph Node positive)
- Surgical resection
- Avoided if supraclavicular node or internal mammary node involvement
- Radiation Therapy
- Surgical resection
- Recurrent Breast Cancer - Distant Metastases (Stage 4 Breast Cancer)
- Endocrine therapy (if Hormone receptor positive)
- ERBB2 (HER2) directed Immunotherapy if positive
- Chemotherapy as directed by biomarkers (e.g. Oncotype DX)
III. Management: Surgical
- Breast Lumpectomy with Breast Radiation
- Mastectomy
- Breast Reconstruction
IV. Management: Chemotherapy
- Indications
- Most beneficial
- Lymph Node involvement
- Primary Breast Cancer larger than 1 cm
- Hormone receptor negative Breast Cancer
- Questionable benefit
- Age over 70 years
- Small, node-negative Breast Cancers (<1 cm)
- Favorable histologic subtypes
- Tubular cancers
- Mucinous cancers
- Most beneficial
- Anthracyclines
- Doxorubicin (Adriamycin) IV q14-21 days for 4-6 cycles
- Combined with Taxane (Docetaxel or Paclitaxel), and cyclophosphamide and/or fluorouracil
- Epirubicin (Ellence) every 21-28 days for 3-8 cycles
- Combined with cyclophosphamide or fluorouracil
- Doxorubicin (Adriamycin) IV q14-21 days for 4-6 cycles
- Taxanes
- Docetaxel IV every 21 days for 3-4 cycles
- Combined with anthracycline (doxorubicin or epirubicin), and cyclophosphamide and/or fluorouracil
- Paclitaxel IV every 7-21 days for 4-12 cycles
- Combined with doxorubicin and cyclophosphamide
- Docetaxel IV every 21 days for 3-4 cycles
V. Management: Hormonal Manipulation (Estrogen inhibition)
- Indications: Suppress Estrogen synthesis
- Hormone receptor positive
- Progesterone receptor positive (possible benefit)
- Hormone receptor indeterminate
- Protocol: Pre-Menopause
- Tamoxifen
- Selective Estrogen Receptor Modulator (SERM)
- Tamoxifen 20 mg orally daily (generic)
- Usually taken for first 5 years after diagnosis (2 years in some cases)
- May be followed by Aromatase inhibitor
- Adverse effects
- Venous Thromboembolism (NNH 200)
- Endometrial Cancer (NNH 250)
- Cataracts (NNH 38)
- Efficacy
- Reduces risk of cancer recurrence by 47%
- NNT 142 to prevent 1 case of invasive Breast Cancer after taking for 5 years
- Gonadotropin-releasing Hormone Agonist (LHRF Agonist)
- Agent: Goserelin (Zoladex) SQ q1-3 months for 2 years
- Tamoxifen
- Protocol: Post-Menopause
- Raloxifene
- Selective Estrogen Receptor Modulator (SERM)
- Raloxifene 60 mg orally daily
- Efficacy
- NNT 111 to prevent 1 case of invasive Breast Cancer after taking for 5 years
- Adverse Effects
- Venous Thromboembolism Risk (as with Tamoxifen)
- Lowers Osteoporosis risk and does not increase risk of Endometrial Cancer
- Aromatase inhibitor
- Agents (typically taken for 5 years, may be as short as 2 years in some cases)
- Anastrozole (Arimidex) 1 mg orally daily (generic)
- Letrozole (Femara) one tablet daily
- Exemestane (Aromasin) 25 mg orally daily
- Efficacy
- NNT 63 to prevent 1 case of invasive Breast Cancer after taking for 5 years
- Adverse Effects
- Osteoporosis (decreases Bone Mineral Density)
- Possible increased cardiovascular disease risk including CVA risk
- Consider as sequential treatment with aromatase inhibitor after Tamoxifen discontinued
- Osteoporosis risk (see Osteoporosis Prevention)
- Avoid in premenopausal women
- Osteoporosis risk
- Risk of Ovulation stimulation and higher risk of pregnancy
- Not as effective as in postmenopausal women
- Agents (typically taken for 5 years, may be as short as 2 years in some cases)
- Raloxifene
VI. Management: Biologics
-
Trastuzumab (Herceptin)
- Monoclonal Antibody improves survival for overexpressors of ERBB2 (previously HER2 gene)
- Herceptin IV given with first dose of Chemotherapy and then every 1-3 weeks for 1 year
- Indicated for Her-2_neu positive, ERBB2 overexpressing patients with metastatic Breast Cancer
- Pertuzumab (Perjeta)
- Neratinib (Nerlynx)
- Oral Tyrosine Kinase inhibitor
- References
VII. Resources
- Adjuvant! for Breast Cancer
- http://www.adjuvantonline.com
- Predicts prognosis and allows comparison of various adjuvant interventions in terms of outcome
VIII. References
- (2019) Presc Lett 26(11): 65
- (2000) NIH Consensus Guidelines
- Golhirsch (2007) Ann Oncol 18(7): 1133-44 [PubMed]
- Maughan (2010) Am Fam Physician 81(11): 1339-46 [PubMed]
- Trayes (2021) Am Fam Physician 104(2): 171-8 [PubMed]