What is the role of radiation therapy (RT) in a patient with stage II (T2N0) triple-negative breast cancer (TNBC) with perineural invasion, status post (s/p) adjuvant chemotherapy?

Radiation Therapy for T2N0 Triple-Negative Breast Cancer with Perineural Invasion Post-Adjuvant Chemotherapy

Radiation therapy should be strongly considered and likely administered in this patient with T2N0 triple-negative breast cancer with perineural invasion following adjuvant chemotherapy, as the combination of high-risk features (TNBC biology, perineural invasion, and T2 tumor size) places this patient at elevated risk for locoregional recurrence despite node-negative status. 1, 2

Risk Stratification in T2N0 Disease

• T2 tumors (>2 cm) automatically place patients in at least intermediate risk (10-50% recurrence) for locoregional failure, even when node-negative. 2

• The presence of perineural invasion is a well-established high-risk feature that increases locoregional recurrence risk and warrants consideration of adjuvant radiation therapy. 1

• Triple-negative biology itself represents an aggressive subtype with higher regional recurrence rates compared to hormone receptor-positive disease, even after appropriate systemic therapy. 3, 4

NCCN Guideline Recommendations for High-Risk T2N0 Disease

• Post-mastectomy or post-lumpectomy radiation therapy may be considered optional for T2N0 breast cancer, but should be strongly considered when additional high-risk features are present, including young age, high grade, lymphovascular invasion, close/positive margins, or aggressive biology. 2

• Regional nodal irradiation (RNI) may be considered for select patients with node-negative disease at high risk, with assessment based on tumor size, lymphovascular invasion, and intrinsic tumor type. 1

• The treatment field should include the chest wall (if mastectomy) or whole breast (if lumpectomy), supraclavicular area, and consideration of infraclavicular region and internal mammary nodes. 1

Triple-Negative Breast Cancer-Specific Considerations

• TNBC demonstrates significantly higher locoregional recurrence rates compared to other breast cancer subtypes, with regional recurrence being particularly problematic. 3

• Prospective randomized data in early-stage TNBC demonstrates that adjuvant chemotherapy plus radiation therapy significantly improves both recurrence-free survival (88.3% vs 74.6%, HR 0.77, P=0.02) and overall survival (90.4% vs 78.7%, HR 0.79, P=0.03) compared to chemotherapy alone at 5 years. 5

• Radiation therapy has been shown to be particularly useful for the management of TNBC, with recommendations for chest wall radiation after mastectomy and regional area radiation as well as breast radiation after breast-conserving surgery. 3

Impact of Perineural Invasion

• Substantial perineural involvement (involvement of more than just a few small sensory nerve branches or large nerve involvement) is an established indication for adjuvant radiotherapy in the NCCN guidelines, though this recommendation originates from basal cell carcinoma data. 1

• Perineural invasion in breast cancer represents extension of disease along nerve pathways and is associated with increased risk of local and regional recurrence. 1

Treatment Algorithm for This Patient

Given the combination of:

• T2 tumor size (intermediate-high risk)
• Node-negative but with perineural invasion (high-risk feature)
• Triple-negative biology (aggressive subtype with higher regional recurrence)
• Completion of adjuvant chemotherapy

Recommended radiation approach:

1. Administer radiation therapy to the chest wall (if mastectomy) or whole breast (if lumpectomy) at standard dosing of 50 Gy in 1.8-2.0 Gy fractions. 1

2. Strongly consider regional nodal irradiation including supraclavicular and infraclavicular areas given the high-risk features despite node-negative status. 1

3. Consider internal mammary nodal irradiation, particularly if the tumor was medially located, though this remains at the discretion of the treating radiation oncologist. 1

4. Use CT-based treatment planning to minimize cardiac and pulmonary toxicity, especially important in TNBC patients who have received anthracycline-based chemotherapy. 1

Critical Caveats

• The presence of three or more high-risk features (which this patient has: T2 size, perineural invasion, TNBC biology) substantially increases locoregional recurrence risk and strengthens the indication for radiation. 2

• Radiation should be delivered after completion of adjuvant chemotherapy to optimize both local control and systemic disease management. 1

• Despite adjuvant radiation therapy, patients with TNBC and high-risk features require close surveillance, as they remain at elevated risk for both locoregional and distant recurrence. 4