NCCN Breast Cancer Treatment Guidelines
Breast cancer requires a multidisciplinary treatment approach integrating surgical oncology, radiation oncology, and medical oncology, with treatment decisions driven by tumor biology (hormone receptor status, HER2 status), anatomic stage, and patient factors. 1, 2
Core Treatment Framework
Initial Assessment Requirements
- Comprehensive pathology evaluation is mandatory, including histologic type, hormone receptor (ER/PR) status, HER2 status, tumor grade, size, and lymph node involvement 2
- Assess left ventricular ejection fraction (LVEF) before initiating any HER2-directed therapy and monitor at regular intervals throughout treatment 3
- Verify pregnancy status in all females of reproductive potential before starting treatment, as trastuzumab exposure during pregnancy causes oligohydramnios, pulmonary hypoplasia, skeletal abnormalities, and neonatal death 3
- For metastatic disease, biopsy accessible metastatic lesions to confirm diagnosis and reassess biological markers 2
Treatment by Molecular Subtype
Hormone Receptor-Positive, HER2-Negative Disease (70% of cases)
- Adjuvant endocrine therapy is the cornerstone to reduce recurrence risk 1, 2, 4
- For premenopausal women: Tamoxifen 5 years ± ovarian suppression/ablation (Category 1) OR aromatase inhibitor 5 years + ovarian suppression/ablation (Category 1) 5
- For postmenopausal women: Aromatase inhibitor 5 years (Category 1) OR tamoxifen 2-3 years followed by aromatase inhibitor to complete 5 years (Category 1) 5
- Add chemotherapy selectively based on recurrence risk assessment using clinical factors and/or multigene assays 1, 2
- The 21-gene recurrence score (Oncotype Dx) is the only clinically validated multigene assay for predicting benefit of adding adjuvant chemotherapy 1
HER2-Positive Disease (15-20% of cases)
- All patients with HER2-positive disease must receive HER2-directed therapy combined with chemotherapy 2, 5, 4
- For adjuvant treatment: Trastuzumab-based therapy for 1 year total 5
- For neoadjuvant treatment: Pertuzumab + trastuzumab + docetaxel for 4-6 cycles achieves pathologic complete response rates of 45.8-66.2% 6
- If residual disease after neoadjuvant therapy: Switch to trastuzumab emtansine for 14 cycles 6
- For metastatic disease: Continue HER2-targeted therapy even after progression 5
- Critical warning: Trastuzumab can cause subclinical and clinical cardiac failure, with highest incidence when combined with anthracyclines 3
Triple-Negative Breast Cancer (15% of cases)
- Chemotherapy is the mainstay of treatment 2, 4
- Triple-negative breast cancer has worse prognosis: 85% 5-year survival for stage I vs 94-99% for hormone receptor-positive and HER2-positive subtypes 4
- Median overall survival for metastatic triple-negative breast cancer is approximately 1 year vs approximately 5 years for other subtypes 4
Surgical and Locoregional Management
Early-Stage Disease (Stage 0-II)
- Options include breast-conserving surgery with radiation therapy OR mastectomy with or without reconstruction 2, 5
- Whole breast radiation therapy is mandatory after breast-conserving surgery 2, 5
- Radiation therapy following breast-conserving surgery decreases both mortality and recurrence 7
- Sentinel lymph node biopsy is appropriate for most breast cancers with clinically negative axillary lymph nodes, avoiding the arm swelling and pain associated with axillary lymph node dissection 7
Locally Advanced Disease (Stage III)
- Post-mastectomy radiation is indicated for high-risk features including N2 disease 2, 5
- For N2 disease, radiation must include chest wall or whole breast plus infraclavicular, supraclavicular, and internal mammary nodes 6
- Critical pitfall: Never base radiation therapy decisions on post-neoadjuvant pathology; always use pre-treatment clinical stage to determine radiation fields 6
Preoperative (Neoadjuvant) Systemic Therapy
Indications and Benefits
- Preoperative systemic therapy facilitates breast conservation, renders inoperable tumors operable, and provides critical prognostic information based on treatment response 2, 5, 6
- Ideal candidates include: Patients with inoperable breast cancer, HER2-positive disease ≥cT2 or ≥cN1, triple-negative breast cancer ≥cT2 or ≥cN1, and patients desiring breast conservation with large tumors 2, 5, 6
Specific Regimens
- For HER2-positive disease: Pertuzumab + trastuzumab + docetaxel for 4-6 cycles 6
- For N2 disease: Neoadjuvant chemotherapy is first-line approach, allowing tumor downstaging and early treatment of micrometastatic disease 6
- Most tumors respond with >50% decrease in tumor size, and approximately 70% of patients experience down-staging 8
Post-Neoadjuvant Management
- Surgery should be performed after completion of neoadjuvant chemotherapy 6
- For N2 disease, axillary lymph node dissection remains necessary even after excellent neoadjuvant response; do not perform sentinel node biopsy alone 6
Metastatic/Stage IV Disease Management
Treatment Goals and Approach
- Primary goals are palliating symptoms, prolonging survival, and maintaining or improving quality of life 2, 5
- For patients with intact primary tumor, the primary approach is systemic therapy, not surgery 2, 5
- Surgery is considered only for palliation of symptoms or impending complications 2
Systemic Therapy Selection
- Treatment selection is based on hormone receptor status, HER2 status, tumor burden, and patient preference 5
- Evaluate response every 2-4 months for endocrine therapy or after 2-4 cycles for chemotherapy 2, 5
- Integrate expert palliative care early from time of metastatic diagnosis 5
Premedication and Monitoring Requirements
For Paclitaxel Administration
- All patients must be premedicated to prevent severe hypersensitivity reactions: Dexamethasone 20 mg PO at 12 and 6 hours before paclitaxel, diphenhydramine 50 mg IV 30-60 minutes prior, and cimetidine 300 mg or ranitidine 50 mg IV 30-60 minutes before 9
- Do not repeat courses until neutrophil count ≥1,500 cells/mm³ and platelet count ≥100,000 cells/mm³ 9
- Reduce dose by 20% for patients experiencing severe neutropenia (neutrophil <500 cells/mm³ for ≥1 week) or severe peripheral neuropathy 9
For Trastuzumab Administration
- Monitor patients during and for 24 hours after administration for infusion reactions and pulmonary toxicity 3
- Interrupt infusion for dyspnea or clinically significant hypotension; discontinue for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome 3
- Monitor cardiac function rigorously during dual HER2 blockade with pertuzumab and trastuzumab 6
Special Populations and Considerations
Hepatic Impairment
- Patients with hepatic impairment are at increased risk of toxicity, particularly grade III-IV myelosuppression 9
- For paclitaxel 24-hour infusion: If transaminases <2× ULN and bilirubin ≤1.5 mg/dL, use 135 mg/m²; if transaminases 2-<10× ULN and bilirubin ≤1.5 mg/dL, reduce to 100 mg/m² 9
Older Patients
- Older patients should not be denied effective therapy based solely on age 2
ER-Low Positive Tumors (1-10%)
- Individualized consideration of risks versus benefits of endocrine therapy is recommended 2