What are the indications for neoadjuvant therapy in breast cancer?

Indications for Neoadjuvant Therapy in Breast Cancer

Any patient with operable breast cancer who would be a candidate for adjuvant systemic chemotherapy can be offered neoadjuvant therapy as a standard treatment option, with equivalent survival outcomes. 1

Primary Goals of Neoadjuvant Therapy

Neoadjuvant systemic therapy serves three critical objectives that directly impact patient outcomes 1:

• Reduce mortality from breast cancer with reduced toxicity 1
• Improve surgical options by downstaging tumors to enable breast-conserving surgery 1
• Acquire early information on tumor response and biology to guide subsequent treatment decisions 1

Specific Clinical Indications

Preferred Indications for Neoadjuvant Cytotoxic Chemotherapy

Neoadjuvant chemotherapy is the preferred approach when:

• Breast-conserving surgery is not initially possible or would result in suboptimal cosmetic outcomes 1
• Tumors express markers predicting good chemotherapy response, including 1:
  • Low or absent hormone receptor status (ER/PR negative)
  • High-grade histology
  • Non-lobular invasive histology
  • High Ki67 proliferation index
  • Luminal B subtype
• HER2-positive disease requiring anti-HER2 therapy with trastuzumab and pertuzumab 2
• Locally advanced breast cancer (stage III) requiring tumor downstaging 1
• Inflammatory breast cancer, where neoadjuvant therapy is standard of care 3

Preferred Indications for Neoadjuvant Endocrine Therapy

Endocrine neoadjuvant therapy is appropriate when:

• Breast-conserving surgery is not initially feasible AND the patient is not a candidate for cytotoxic chemotherapy 1
• Predictive markers favor endocrine responsiveness, including 1:
  • ER and PR strongly positive
  • Low-grade histology
  • Invasive lobular histology
  • Low Ki67 proliferation index

Treatment Selection Algorithm

Step 1: Assess Surgical Candidacy

• If breast-conserving surgery is feasible with acceptable cosmesis → neoadjuvant therapy is optional but can still be offered 1
• If breast-conserving surgery is not feasible or would result in poor cosmesis → neoadjuvant therapy is preferred 1

Step 2: Evaluate Tumor Biology

• HER2-positive disease → neoadjuvant chemotherapy with trastuzumab and pertuzumab plus docetaxel 2
• Triple-negative or hormone receptor-negative disease → neoadjuvant chemotherapy (anthracycline and taxane-based) 1, 3
• Hormone receptor-positive/HER2-negative with aggressive features (high Ki67, high grade, luminal B) → neoadjuvant chemotherapy 1
• Hormone receptor-positive/HER2-negative with favorable features (low Ki67, low grade, lobular) AND patient unfit for chemotherapy → neoadjuvant endocrine therapy 1

Step 3: Consider Patient Fitness

• Fit patients with locally advanced disease → neoadjuvant chemotherapy 1
• Unfit patients with hormone-sensitive disease → neoadjuvant endocrine therapy 1

Standard Chemotherapy Regimens

Anthracycline and taxane-based regimens are the backbone of neoadjuvant chemotherapy, administered either sequentially or in combination 1:

• Combined or sequential use of anthracyclines and taxanes are both acceptable 1
• For HER2-positive disease, trastuzumab must be incorporated, with pertuzumab added for improved pathologic complete response rates 2
• Concomitant anthracycline and trastuzumab should only occur in clinical trials due to cardiac toxicity concerns 1

Critical Timing Considerations

Surgery should be performed 2-4 weeks after completion of neoadjuvant chemotherapy to allow adequate response assessment 4. For neoadjuvant endocrine therapy, treatment duration should be at least 6 months or until maximum response is achieved 4.

Common Pitfalls to Avoid

• Do not delay neoadjuvant therapy initiation beyond 2-4 weeks after diagnosis and staging completion 4
• Do not assume neoadjuvant therapy is only for locally advanced disease—it is appropriate for any patient who would receive adjuvant chemotherapy 1
• Do not use neoadjuvant endocrine therapy in patients who are candidates for chemotherapy unless specific contraindications exist 1
• Do not omit HER2-targeted therapy in HER2-positive disease, as dual blockade with pertuzumab and trastuzumab significantly improves outcomes 2

Survival Equivalence

Meta-analyses demonstrate no difference in survival or overall disease progression between neoadjuvant and adjuvant therapy, establishing neoadjuvant treatment as a standard option rather than an inferior alternative 1. Patients achieving pathologic complete response have significantly improved long-term outcomes 1, 5.