What is the best treatment for a patient with triple negative breast cancer Stage 3B?

Treatment for Stage 3B Triple Negative Breast Cancer

For a patient with Stage 3B triple negative breast cancer, neoadjuvant chemotherapy with taxanes, carboplatin, anthracyclines, and cyclophosphamide combined with concurrent pembrolizumab is the preferred treatment approach, followed by surgery and continued adjuvant pembrolizumab regardless of pathologic response. 1, 2

Neoadjuvant Treatment Strategy

Primary Regimen (Preferred)

• The National Comprehensive Cancer Network recommends the KN522 trial protocol as the preferred neoadjuvant regimen for stage II/III TNBC: chemotherapy with taxanes, carboplatin, anthracyclines, and cyclophosphamide, combined with concurrent pembrolizumab. 1, 2
• The benefit from pembrolizumab is independent of PD-L1 status, meaning all patients should receive it regardless of PD-L1 testing results. 1, 2
• This approach allows for tumor downstaging for surgical purposes, assessment of pathologic complete response (pCR), and opportunity to tailor adjuvant therapy based on response. 1, 2

Alternative Sequential Approach

• Sequential anthracycline-based regimens followed by taxanes represent an evidence-based alternative option if the preferred regimen cannot be administered. 1, 2
• Weekly paclitaxel plus carboplatin followed by anthracycline chemotherapy has demonstrated a 60% pathologic complete response rate in stage I-III TNBC, though with significant hematologic toxicity. 3

Post-Neoadjuvant Management

For Patients Achieving Pathologic Complete Response

• Continue adjuvant pembrolizumab regardless of the extent of response to neoadjuvant chemotherapy plus pembrolizumab. 1, 2
• The FDA has approved pembrolizumab for high-risk early-stage TNBC in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery. 4

For Patients with Residual Disease After Neoadjuvant Therapy

• If germline BRCA1/2 wild-type, administer adjuvant capecitabine for 6-8 cycles. 5, 1
• The CREATE-X trial demonstrated that patients with triple-negative breast cancer and residual disease after neoadjuvant therapy had improved recurrence-free survival (HR 0.53, P = .02) and overall survival (HR 0.55, P = .03) with capecitabine. 5
• The capecitabine dosage used (1,250 mg/m² twice daily on days 1-14 of a 21-day cycle) is associated with higher toxicity in patients ≥65 years old, requiring dose adjustment consideration. 5
• Continue adjuvant pembrolizumab in addition to capecitabine. 1, 2

For Patients with Germline BRCA1/2 Mutations

• PARP inhibitors may be considered in the adjuvant setting for patients with germline BRCA1/2 mutations and residual disease. 1

Critical Treatment Considerations

Genetic Testing

• All patients with TNBC should undergo genetic testing for germline BRCA1/2 mutations, as this impacts treatment decisions. 1

Toxicity Management

• Hand-foot syndrome is the most frequent adverse event with capecitabine, occurring in 73.4% of patients, including 11.1% with grade 3 events. 5
• Grade ≥3 neutropenia (96%), anemia (40%), and thrombocytopenia (15%) are common with carboplatin-containing regimens, with neutropenic fever in 22% of patients. 3
• Patients should be monitored closely for immune-related adverse events when receiving pembrolizumab. 6

Common Pitfalls to Avoid

• Do not withhold pembrolizumab based on PD-L1 status in the neoadjuvant setting—the benefit is independent of PD-L1 expression. 1, 2
• Do not discontinue adjuvant pembrolizumab in patients who achieved pathologic complete response—continuation is recommended regardless of response. 1, 2
• Do not use capecitabine in patients with germline BRCA1/2 mutations who have residual disease—consider PARP inhibitors instead. 1