What are the primary treatment approaches for breast cancer?

Primary Treatment Approaches for Breast Cancer

The primary treatment approaches for breast cancer include surgery (breast-conserving surgery or mastectomy), radiation therapy, and systemic therapies (endocrine therapy, chemotherapy, and targeted therapies), with treatment selection based on tumor characteristics, stage, and receptor status. 1

Surgical Management

• Breast-conserving surgery (BCS) with radiotherapy or mastectomy are the standard surgical approaches for early breast cancer 1
• Contraindications to breast-conserving surgery include multicentric tumors, large tumors (>3-4 cm) in small breasts, retro-areolar localization, and tumor-involved margins after resection 1
• Sentinel node biopsy should only be performed in centers with documented experience and accuracy, and should not be performed in cases with palpable axillary nodes, T3 or T4 tumors, multicentric tumors, prior axillary surgery, after breast reconstruction, during pregnancy/lactation, or after neoadjuvant systemic treatment outside clinical trials 1

Radiation Therapy

• Breast radiotherapy is strongly recommended after breast-conserving surgery [Level I, A evidence] 1
• Post-mastectomy radiotherapy is recommended for patients with four or more positive axillary nodes [Level II, B evidence] and is suggested for T3 tumors independent of nodal status [Level III, B evidence] 1
• For patients >70 years with receptor-positive invasive breast cancer (maximum stage pT1N0) and clear postoperative margins, adjuvant tamoxifen may be considered instead of radiation therapy [Level II, B evidence] 1

Systemic Therapy Approach

Adjuvant Systemic Therapy

Treatment decisions are based primarily on two factors 1:

1. Endocrine responsiveness of tumor tissue
2. Risk of relapse

• Tumors with clear expression of ER and/or PgR are considered endocrine responsive 1
• Patients with endocrine responsive tumors may receive endocrine treatment alone or combined with chemotherapy 1
• Patients with uncertain endocrine responsiveness (low receptor levels, lack of PgR, HER2 overexpression) typically receive both endocrine therapy and chemotherapy 1
• Patients with endocrine non-responsive tumors derive greater benefit from chemotherapy and should not receive endocrine therapy 1
• Patients with HER2 overexpression/amplification should be considered for adjuvant trastuzumab treatment 1, 2

Primary (Neoadjuvant) Systemic Therapy

• Primary systemic therapy is indicated for locally advanced breast cancer (stages IIIA-IIIB-IIIC) [Level III, B evidence] 1
• It can also be used for large operable breast cancers to allow breast-conserving surgery [Level I, A evidence] 1
• Before primary systemic therapy, a biopsy for histology and analysis of predictive factors should be performed, along with full clinical staging to rule out metastatic disease 1
• Primary systemic therapy can employ chemotherapy or endocrine therapy based on predictive factors, and should be followed by surgery, radiotherapy, and postoperative systemic treatment 1

Treatment by Breast Cancer Subtype

Hormone Receptor-Positive/HER2-Negative (70% of patients)

• Endocrine therapy is the cornerstone of treatment 3, 4
• Options include:
  • Selective estrogen receptor modulators (SERMs): tamoxifen, raloxifene, toremifene 3
  • Selective estrogen receptor degraders (SERDs): fulvestrant, elacestrant 3
  • Aromatase inhibitors: anastrozole, letrozole, exemestane 3
• Some patients may also receive chemotherapy based on risk factors 4
• CDK4/6 inhibitors are used in metastatic setting 3

HER2-Positive (15-20% of patients)

• Treatment includes HER2-targeted antibody or small-molecule inhibitor therapy combined with chemotherapy 4
• Trastuzumab is indicated for adjuvant treatment of HER2-overexpressing node-positive or high-risk node-negative breast cancer 2
• For metastatic disease, trastuzumab is indicated in combination with paclitaxel for first-line treatment or as a single agent for patients who have received one or more chemotherapy regimens 2

Triple-Negative (15% of patients)

• Chemotherapy is the primary systemic treatment approach 4
• Higher risk of recurrence than other subtypes, with 85% 5-year breast cancer-specific survival for stage I triple-negative tumors vs. 94-99% for hormone receptor-positive and HER2-positive tumors 4
• Immunotherapy and PARP inhibitors are emerging options for specific subsets of patients 3, 5

Common Pitfalls to Avoid

• Underestimating the importance of multidisciplinary treatment planning that integrates local and systemic therapies 1
• Failing to assess hormone receptor and HER2 status, which are crucial for treatment selection 1
• Omitting radiation therapy after breast-conserving surgery, which reduces local recurrence risk by two-thirds and has a beneficial effect on survival 1
• Not considering primary systemic therapy for locally advanced disease or large operable tumors that might benefit from downstaging 1
• Administering endocrine therapy to patients with endocrine non-responsive tumors 1

Risk Assessment for Treatment Selection

• Risk categories (low, intermediate, high) help guide treatment decisions 1
• Factors considered include tumor size, grade, lymph node status, peritumoral vascular invasion, HER2 status, and age 1
• Decision-making tools like "Adjuvant! Online" and National Comprehensive Cancer Network guidelines can help with treatment decisions 1

Treatment for breast cancer has evolved to a personalized approach based on molecular subtypes, providing improved outcomes and quality of life for patients across all disease stages 6, 5.