What is the role of adjuvant radiation therapy after mastectomy?

From the Guidelines

Adjuvant radiation therapy after mastectomy is recommended for patients with high-risk features, including those with 4 or more positive axillary lymph nodes, to reduce the risk of local recurrence and improve survival. The decision to use post-mastectomy radiation therapy (PMRT) should be based on a risk-adaptive strategy that balances the potential benefits of PMRT against its potential harms, considering factors such as patient age, estimated life expectancy, tumor size, axillary lymph node burden, tumor grade, lymphovascular invasion, biomarker or receptor status, and planned systemic therapy 1.

Key Considerations

• PMRT is always recommended for high-risk patients, including those with involved resection margins, 4 involved axillary lymph nodes, and T3–T4 tumours independent of the nodal status 1.
• For patients with 1–3 positive axillary lymph nodes, PMRT should be considered for routine use, as it reduces the 10-year risk of any recurrence and the 20-year risk of breast cancer-related mortality 1.
• The standard regimen involves delivering external beam radiation to the chest wall and regional lymph nodes at doses of 45-50 Gy over 5-6 weeks, with possible additional boost doses to areas at highest risk.
• Treatment usually begins 4-8 weeks after surgery or after completion of adjuvant chemotherapy if that is part of the treatment plan.

Benefits and Risks

• PMRT reduces the risk of locoregional recurrence and improves survival in high-risk patients 1.
• However, PMRT can also increase the risk of lymphedema, especially in patients who undergo axillary lymph node dissection, and can worsen cosmetic results and increase the risk of both short- and long-term complications 1.
• Modern techniques have significantly reduced the risks associated with PMRT, but long-term cardiac or pulmonary complications can still occur 1.

Multidisciplinary Approach

• The decision for post-mastectomy radiation should be made as part of a multidisciplinary approach, considering individual patient factors and tumor characteristics 1.
• A risk estimation should include assessment of patient age, estimated life expectancy, tumor size, axillary lymph node burden, tumor grade, lymphovascular invasion, biomarker or receptor status, and planned systemic therapy 1.

From the Research

Role of Adjuvant Radiation Therapy after Mastectomy

The role of adjuvant radiation therapy after mastectomy is defined in high-risk patients with locally advanced tumors, positive margins, and unfavorable biology 2.

• High-Risk Patients: In patients with four or more positive lymph nodes or extracapsular extension, regional lymph node irradiation is indicated regardless of the surgery type (breast-conserving surgery or mastectomy) 2.
• Intermediate-Risk Patients: The benefit of postmastectomy radiotherapy in intermediate-risk patients (T3N0 tumors) remains a matter of controversy 2.
• Locoregional Recurrence: Radiotherapy after breast-conserving surgery lowers the locoregional recurrence rate compared with surgery alone and improves the overall survival rate 2.
• Neoadjuvant Systemic Therapy: In patients treated with neoadjuvant systemic therapy and mastectomy, adjuvant radiotherapy should be administered in cases of clinical stage III and/or ≥ypN1 2.

Efficacy of Postmastectomy Radiation Therapy

Postmastectomy radiation therapy (PMRT) can reduce the risk of locoregional recurrence in high-risk breast cancer patients 3.

• Locoregional Failure: The crude rate of local failure as the first site of failure for patients randomized to receive chemotherapy only was 14%; for those randomized to receive both chemotherapy and radiotherapy it was 5% (P = .03) 4.
• Distant Failure: Radiation also was associated with improved distant control (RR=0.75; 95% CI, 0.58 to 0.96) 5.
• Overall Survival: OS also improved with radiation (RR=0.68; 95% CI, 0.53 to 0.85) 5.

Timing of Postmastectomy Radiotherapy

The timing of the initiation of radiotherapy both after mastectomy and after the completion of adjuvant chemotherapy is crucial for patients with high-risk breast cancer 6.

• Surgery-RT Interval: An SRI of >210 days was independently associated with higher DM, lower OS, and lower DFS than SRI of <180 or 180-210 days 6.
• Chemotherapy-RT Interval: A CRI of more than 42 days was independently associated with higher DM, lower OS, and lower DFS than a CRI of <28 or 28-42 days 6.