What are the recommended adjuvant therapies for breast cancer?

Recommended Adjuvant Therapies for Breast Cancer

Adjuvant therapy for breast cancer should be tailored based on tumor characteristics including hormone receptor status, HER2 status, risk category, and patient factors, with endocrine therapy, chemotherapy, and targeted therapies used alone or in combination depending on these factors. 1

Risk Assessment and Treatment Decision Framework

• Risk categorization helps determine appropriate adjuvant therapy, with factors including tumor size, grade, lymph node status, peritumoral vascular invasion, HER2 status, and age 1
• Low-risk tumors: node-negative with pT ≤2 cm, grade 1, no peritumoral vascular invasion, HER2-negative, age ≥35 years 1
• Intermediate-risk tumors: node-negative with at least one high-risk feature (pT >2 cm, grade 2-3, peritumoral vascular invasion, HER2 positive, age <35) or 1-3 positive nodes with HER2-negative disease 1
• High-risk tumors: 1-3 positive nodes with HER2-positive disease or ≥4 positive nodes 1

Endocrine Therapy

For Premenopausal Patients:

• Tamoxifen alone (20 mg/day for 5 years) or combined with ovarian function suppression is indicated for hormone receptor-positive disease 1
• Gonadotropin-releasing hormone analogs (GnRHAs) like goserelin (3.6 mg subcutaneously monthly) should be given for at least 2 years for reversible ovarian suppression 1
• Aromatase inhibitors alone are contraindicated in premenopausal women due to lack of efficacy evidence 1
• Combination of GnRHA and aromatase inhibitors is not currently indicated in the adjuvant setting 1

For Postmenopausal Patients:

• Adjuvant endocrine therapy should include an aromatase inhibitor (anastrozole 1 mg daily, letrozole 2.5 mg daily, or exemestane 25 mg daily) at some point 1
• Options include upfront aromatase inhibitor for 5 years, tamoxifen for 2-3 years followed by aromatase inhibitor, or tamoxifen for 5 years followed by extended aromatase inhibitor therapy 1
• Aromatase inhibitors have shown improved disease-free survival compared to tamoxifen 1
• Women on aromatase inhibitors should receive vitamin D and calcium supplements due to risk of bone loss 1

Chemotherapy

• Recommended for intermediate or high-risk patients with endocrine non-responsive tumors and in combination with endocrine therapy for hormone-responsive tumors with higher risk features 1
• Common adjuvant chemotherapy regimens include: 1
  • AC (doxorubicin/cyclophosphamide): 4 cycles over 3 weeks per cycle
  • AC followed by T (paclitaxel or docetaxel): 4 cycles each
  • FEC (fluorouracil, epirubicin, cyclophosphamide): 6 cycles over 3 weeks per cycle
  • FEC followed by docetaxel: 3 cycles each
  • TAC (docetaxel, doxorubicin, cyclophosphamide): 6 cycles over 3 weeks per cycle 2
• For adjuvant treatment of node-positive breast cancer, docetaxel 75 mg/m² is administered 1 hour after doxorubicin 50 mg/m² and cyclophosphamide 500 mg/m² every 3 weeks for 6 courses 2
• For adjuvant node-positive breast cancer, paclitaxel 175 mg/m² intravenously over 3 hours every 3 weeks for 4 courses is administered sequentially to doxorubicin-containing combination chemotherapy 3

HER2-Targeted Therapy

• Trastuzumab is recommended for patients with HER2-positive tumors in addition to chemotherapy 1, 4
• For stage I HER2-positive breast cancer, paclitaxel/trastuzumab is the preferred regimen 1
• For node-positive HER2-positive disease, dual blockade with pertuzumab and trastuzumab is recommended 1
• Standard duration of adjuvant trastuzumab is 1 year, though 6 months may be considered for patients with low risk of relapse and comorbidities 1, 4
• Trastuzumab should be administered concurrently with paclitaxel but should not be used concurrently with anthracyclines due to cardiotoxicity risk 4

Special Considerations for Different Subtypes

Triple-Negative Breast Cancer (TNBC):

• Standard anthracycline-based regimens followed by taxanes are recommended 1
• Dose-dense chemotherapy schedules are preferred 1

HR-positive/HER2-negative High-Risk Disease:

• CDK4/6 inhibitors (abemaciclib, ribociclib) may be considered for high-risk patients with 4+ positive nodes or 1-3 nodes with T3 tumors and/or grade 3 histology 1
• For patients with germline BRCA1/2 mutations and HER2-negative tumors, adjuvant olaparib for 1 year is recommended 1

Sequencing of Therapies

• When combining chemotherapy with tamoxifen, tamoxifen should be started after completion of chemotherapy 1
• The optimal timing of aromatase inhibitors in relation to chemotherapy (concurrent vs. sequential) remains unclear 1
• GnRH analogs can be started concurrently with chemotherapy in premenopausal patients 1
• For patients eligible for both olaparib and CDK4/6 inhibitors, sequential approach is suggested with PARP inhibitor concurrent with endocrine therapy for 1 year, followed by CDK4/6 inhibitor 1

Duration of Therapy

• Endocrine therapy duration varies by disease stage: 5 years for stage I, with consideration of extended therapy (5-10 years total) for higher stages, especially node-positive disease 1
• Trastuzumab is typically given for 1 year in the adjuvant setting 1, 4
• Olaparib for germline BRCA mutation carriers is given for 1 year 1

Common Pitfalls to Avoid

• Underestimating the importance of risk stratification in treatment selection 1, 5
• Administering endocrine therapy to patients with endocrine non-responsive tumors 1, 5
• Using aromatase inhibitors alone in premenopausal women 1
• Concurrent use of trastuzumab with anthracyclines due to increased cardiotoxicity 4
• Failing to provide calcium and vitamin D supplementation to patients on aromatase inhibitors 1