What is the management of triple negative breast cancer?

Management of Triple-Negative Breast Cancer

Early-Stage TNBC (Stages I-III)

For stage II-III triple-negative breast cancer, neoadjuvant chemotherapy with dose-dense anthracycline and taxane-based regimens is the preferred approach before definitive surgery. 1

Neoadjuvant Chemotherapy Strategy

• Dose-dense anthracycline and taxane combinations (such as epirubicin/cyclophosphamide followed by docetaxel, or sequential regimens) are the standard neoadjuvant approach for stage II-III disease, achieving pathological complete response (pCR) rates exceeding 20%. 1, 2

• Platinum-based regimens (such as epirubicin, cisplatin, and fluorouracil) represent an important alternative option, particularly for tumors with BRCA-like features, with studies showing pCR rates of 40% in triple-negative disease. 2, 3

• For very small tumors (<5 mm, stage I), surgical excision alone may be appropriate, though nearly half of experts still recommend adjuvant chemotherapy even for these minimal tumors. 1

Surgical Management

• Breast-conserving therapy with adequate margins is appropriate for TNBC given its characteristic expanding growth pattern without extensive intraductal spread. 2

• Sentinel lymph node biopsy is standard for clinically node-negative patients at initial presentation. 1

• For patients with clinically positive nodes who receive neoadjuvant chemotherapy, sentinel lymph node biopsy may be considered if nodes become clinically negative after treatment. 1

• Axillary lymph node dissection is recommended for residual nodal disease after neoadjuvant therapy, especially for macrometastases >2mm. 1

Radiation Therapy

• Post-mastectomy radiation should be considered for patients with positive lymph nodes or positive/close margins. 1

• Post-lumpectomy radiation to the breast is standard after breast-conserving surgery. 4

Adjuvant Therapy Considerations

• For patients with germline BRCA1/2 mutations and high-risk early-stage TNBC, adjuvant olaparib for 1 year should be considered. 1

• Pembrolizumab in combination with chemotherapy as neoadjuvant treatment, followed by pembrolizumab as a single agent adjuvant after surgery, is FDA-approved for high-risk early-stage TNBC. 5

Metastatic TNBC

First-Line Treatment

For PD-L1-positive metastatic TNBC (CPS ≥10), immune checkpoint inhibitor plus chemotherapy (atezolizumab plus nab-paclitaxel or pembrolizumab plus chemotherapy) is the recommended first-line therapy. 4, 6, 5

• This combination demonstrates improved progression-free survival compared to chemotherapy alone and represents a strong evidence-based recommendation. 4, 6

• For PD-L1-negative disease, single-agent chemotherapy is preferred for first-line treatment to minimize toxicity. 4, 6

• Combination chemotherapy may be offered only for symptomatic or immediately life-threatening disease where time may allow only one potential chance for therapy. 4, 6

Chemotherapy Selection

• Taxanes (paclitaxel or docetaxel) are preferred first-line options if not previously used in the adjuvant setting. 6

• Anthracyclines (doxorubicin or epirubicin) are recommended if not previously administered. 6

• Platinum agents (carboplatin or cisplatin) with or without taxanes are appropriate options, with selection based on individual risk-benefit assessment, recognizing increased toxicity including nausea, vomiting, and anemia. 4, 6

Second-Line and Beyond

For patients who have received at least two prior therapies for metastatic disease, sacituzumab govitecan is strongly recommended, with significant improvements in both progression-free survival and overall survival. 4, 6

• For patients with germline BRCA1/2 mutations, oral PARP inhibitors (olaparib or talazoparib) are recommended rather than chemotherapy in the first-through third-line setting. 4, 6

• Note that PARP inhibitor trials made no direct comparison with taxanes, anthracyclines, or platinums; comparative efficacy against these compounds is unknown. 4

Treatment Sequencing Algorithm

1. First-line:

   • PD-L1 positive (CPS ≥10): Checkpoint inhibitor + chemotherapy 4, 6
   • PD-L1 negative: Single-agent chemotherapy 4, 6

2. Subsequent lines (if germline BRCA1/2 mutation present): PARP inhibitor 4, 6

3. After ≥2 prior therapies: Sacituzumab govitecan 4, 6

4. Additional options: Sequential single-agent chemotherapy (anthracyclines if previously treated with taxanes and vice versa, capecitabine, gemcitabine, eribulin) 6

Critical Monitoring

• Patients receiving checkpoint inhibitors must be monitored closely for immune-related adverse events, which can affect any organ system. 6

• Sequential single-agent chemotherapy is generally preferred over combination regimens to minimize toxicity, except in cases of visceral crisis or rapidly progressing disease. 6

Common Pitfalls

• Avoid delaying surgery during neoadjuvant chemotherapy if there is evidence of tumor progression; modify the regimen or proceed to surgery without losing the opportunity for potentially effective treatment. 2

• Do not routinely recommend prophylactic contralateral mastectomy based solely on TNBC status; this should only be considered for patients with germline BRCA1/2 mutations, young age, or strong family history. 1

• Bevacizumab combined with chemotherapy has shown improved progression-free survival but not overall survival, limiting its routine recommendation. 6