When is neoadjuvant chemotherapy (chemo) recommended in triple negative breast cancer?

Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer

Neoadjuvant chemotherapy is recommended for all stage II and III triple-negative breast cancer (TNBC), and should be strongly considered for stage I disease with tumors ≥1 cm or node-positive disease. 1, 2, 3

Stage-Specific Recommendations

Stage II-III TNBC (Preferred Approach)

• Neoadjuvant therapy is the standard of care for stage II and III TNBC, allowing for tumor downstaging, assessment of pathologic complete response (pCR), and the opportunity to tailor post-surgical therapy based on treatment response 1, 3, 4
• The preferred regimen combines chemotherapy (taxanes, carboplatin, anthracyclines, and cyclophosphamide) with concurrent pembrolizumab, based on the KEYNOTE-522 trial protocol 2, 3, 4
• The benefit from pembrolizumab is independent of PD-L1 status 3, 4
• Sequential anthracycline-based regimens followed by taxanes remain an evidence-based alternative option 2, 3, 4

Stage I TNBC

• For tumors ≥1 cm or node-positive disease, neoadjuvant chemotherapy should be strongly considered 1
• The threshold for recommending chemotherapy in TNBC is <5 mm tumor size 1
• For higher-risk stage I disease, consider adding carboplatin and pembrolizumab to the chemotherapy backbone 3, 4

Locally Advanced and Inflammatory Breast Cancer

• Neoadjuvant chemotherapy is mandatory for locally advanced breast cancer (typically >5 cm with regional/metastatic involvement or chest wall/skin involvement) 1
• Inflammatory breast cancer requires neoadjuvant therapy as standard of care, followed by mastectomy if operable after induction treatment 1

Clinical Advantages Supporting Neoadjuvant Approach

Surgical Benefits

• Neoadjuvant therapy increases breast conservation eligibility by 14% absolute, with a 42% conversion rate from mastectomy-only candidates to breast-conserving therapy (BCT) candidates 5
• BCT is successful with tumor-free margins in 93-94% of patients who become eligible and choose this option 5
• Allows for downstaging of both breast tumors and axillary disease, potentially avoiding axillary dissection in patients who convert from clinically positive to negative nodes 1

Prognostic and Treatment Planning Benefits

• Pathologic complete response (pCR) serves as a strong prognostic marker and surrogate endpoint for event-free survival, particularly in TNBC 6, 7, 8
• Patients achieving pCR have significantly improved disease-specific survival 9
• Response assessment enables tailoring of post-surgical adjuvant therapy based on residual disease burden 1, 2

Post-Neoadjuvant Management

For Patients with Residual Disease

• Adjuvant capecitabine for 6-8 cycles should be offered to patients with residual invasive disease after standard anthracycline- and taxane-based neoadjuvant therapy, particularly for hormone receptor-negative disease 1, 2, 3
• The capecitabine dosage is 1,250 mg/m² orally twice daily on days 1-14 of a 21-day cycle, though this is associated with higher toxicity in patients ≥65 years old 1
• Continue adjuvant pembrolizumab regardless of response to neoadjuvant chemotherapy plus pembrolizumab 3, 4

For Patients Achieving pCR

• No additional chemotherapy is required beyond completion of the planned neoadjuvant regimen 2
• Continue pembrolizumab if used in the neoadjuvant setting 3, 4

Common Pitfalls and Caveats

• Do not delay neoadjuvant therapy for stage II-III TNBC—the evidence strongly supports this as preferred over adjuvant chemotherapy for these stages 1, 3
• The 2021 St. Gallen consensus recommended against routine use of immune checkpoint inhibitors pending maturation of survival data 1, but more recent guidelines now support pembrolizumab based on KEYNOTE-522 results 2, 3, 4
• While pCR rates are used for drug development and accelerated approval, the St. Gallen panel noted that pCR alone is not the appropriate endpoint for defining standard regimens—longer-term disease-free and overall survival data should guide treatment decisions 1
• Even tumors as small as 2-5 cm may warrant neoadjuvant therapy if lumpectomy would result in substantial cosmetic defect 1
• Genetic testing for germline BRCA1/2 mutations should be performed in all TNBC patients, as this may influence adjuvant therapy decisions (PARP inhibitors for mutation carriers with residual disease) 3