What is the post-operative plan for a patient with stage 2B (T2N1M0) triple-negative breast cancer (TNBC) who has undergone neoadjuvant chemotherapy and a modified radical mastectomy (MRM) on the right side?

Post-Operative Management for Stage 2B TNBC After Neoadjuvant Chemotherapy and Modified Radical Mastectomy

Complete adjuvant pembrolizumab to one year total duration regardless of pathologic response, add adjuvant capecitabine for 6-8 cycles if residual disease is present and germline BRCA1/2 wild-type, deliver post-mastectomy radiation therapy to chest wall and regional nodes, and test for germline BRCA1/2 mutations to guide potential olaparib therapy. 1, 2, 3

Immediate Post-Operative Systemic Therapy Decisions

Continuation of Pembrolizumab (Priority #1)

• Continue adjuvant pembrolizumab to complete one year total duration from neoadjuvant start, regardless of whether pathologic complete response (pCR) was achieved. 1, 2
• The KEYNOTE-522 protocol demonstrated event-free survival benefit (HR 0.63,95% CI 0.48-0.82, P<0.001) with pembrolizumab continuation even in patients achieving pCR. 1
• This is independent of PD-L1 status and applies to all stage II-III TNBC patients. 1

Adjuvant Capecitabine for Residual Disease

• If surgical pathology shows residual invasive disease (non-pCR) AND the patient is germline BRCA1/2 wild-type, add capecitabine 1,250 mg/m² PO twice daily on days 1-14 of 21-day cycles for 6-8 cycles. 2, 3
• This improves recurrence-free survival (HR 0.53, P=0.02) and overall survival (HR 0.55, P=0.03) in TNBC with residual disease. 2
• Do not withhold capecitabine based on tolerability concerns—the survival benefit is substantial. 3

Germline BRCA1/2 Testing and Olaparib

• Test all TNBC patients for germline BRCA1/2 mutations immediately post-operatively if not already done. 2
• If germline BRCA1/2 mutation is present AND there is residual disease (≥pT2 or ≥pN1) after neoadjuvant chemotherapy, add adjuvant olaparib for 1 year after completing chemotherapy. 2
• Olaparib is NOT indicated if pCR was achieved, even with BRCA mutation. 2

Post-Mastectomy Radiation Therapy

Mandatory Radiation Indications

• Deliver post-mastectomy radiation therapy to chest wall, supraclavicular nodes, and infraclavicular nodes for this T2N1 patient. 4
• Radiation is mandatory for node-positive disease (N1) after mastectomy, as it provides both disease-free and overall survival advantage. 4
• Strongly consider including internal mammary nodes in the radiation field, particularly for medially located tumors or when internal mammary nodes were involved. 4

Timing and Concurrent Therapy

• Schedule radiation 3-4 weeks after final chemotherapy cycle to allow count recovery. 1
• Pembrolizumab and capecitabine (if indicated) can be administered concurrently with radiation therapy. 4

Axillary Management Considerations

If Residual Axillary Disease Present

• The modified radical mastectomy already included level I/II axillary dissection, which is appropriate for this N1 patient. 4
• No additional axillary surgery is needed if adequate level I/II dissection was performed. 4

Critical Pathology Review

• Confirm the number of positive nodes and presence/absence of extracapsular extension in the surgical specimen. 4
• This information guides radiation field design and intensity. 4

Surveillance Protocol

Structured Follow-Up Schedule

• History and physical examination every 4-6 months for 5 years, then annually. 4
• Annual mammography of contralateral breast (ipsilateral breast removed). 4
• Do not perform routine imaging (CT, PET, bone scans) for asymptomatic patients—these are not recommended for surveillance. 4

High-Risk Monitoring Considerations

• Even patients achieving pCR remain at risk for early recurrence within 3 years, particularly with initial cN1 or higher disease. 5
• Maintain heightened clinical vigilance during the first 3 years post-surgery, as TNBC recurrences tend to occur early. 5
• Patients with residual disease after neoadjuvant therapy have significantly higher recurrence risk and warrant closer monitoring. 6

Common Pitfalls to Avoid

Treatment Sequencing Errors

• Do not delay radiation therapy—schedule it promptly after chemotherapy completion. 2
• Do not omit pembrolizumab continuation based on achieving pCR; the benefit persists regardless of pathologic response. 1, 2

Inappropriate Therapy Omissions

• Do not substitute axillary radiation for completed axillary dissection in this node-positive patient. 3
• Do not withhold capecitabine in patients with residual disease who are BRCA wild-type—this is a proven survival benefit. 3

Surveillance Mistakes

• Avoid false reassurance from pCR—these patients still require standard surveillance as early recurrences can occur. 5
• Do not order routine staging scans (CT chest/abdomen/pelvis, bone scans) in asymptomatic patients—this increases false positives without survival benefit. 4

Algorithm Summary

Step 1: Review surgical pathology for residual disease (pCR vs. non-pCR) and confirm germline BRCA1/2 status.

Step 2: Continue pembrolizumab to complete 1 year total duration (all patients). 1, 2

Step 3: If residual disease + BRCA wild-type → Add capecitabine for 6-8 cycles. 2, 3

Step 4: If residual disease + BRCA mutation → Add olaparib for 1 year after chemotherapy completion. 2

Step 5: Deliver post-mastectomy radiation to chest wall and regional nodes (mandatory for N1 disease). 4

Step 6: Initiate structured surveillance with clinical exams every 4-6 months and annual contralateral mammography. 4