What are the indications for adjuvant radiotherapy (RT) in breast cancer and in which cases can RT be avoided?

Indications for Adjuvant Radiotherapy in Breast Cancer

Radiotherapy after breast-conserving surgery is mandatory for invasive breast cancer regardless of tumor characteristics, as it reduces both local recurrence and breast cancer mortality, with the single exception being women ≥70 years old with T1, node-negative, ER-positive tumors receiving endocrine therapy. 1

After Breast-Conserving Surgery (Lumpectomy)

Standard Indications for RT

Invasive Breast Cancer:

• RT must be systematically performed after lumpectomy for all invasive carcinomas, as it provides a 15.7% absolute decrease in local recurrence and 3.8% decrease in 15-year breast cancer mortality 2, 3
• Hypofractionated RT (42.5 Gy in 16 fractions or 40 Gy in 15 fractions) is now the preferred standard approach for whole-breast irradiation, achieving equivalent or better outcomes than conventional fractionation 1
• A boost dose to the tumor bed is required for patients younger than 50 years 3

Ductal Carcinoma In Situ (DCIS):

• RT must be systematically performed after lumpectomy for DCIS, providing approximately 60% reduction in ipsilateral breast recurrence 4, 5
• At 20 years follow-up, RT provides 12% absolute risk reduction in breast events, though this does not translate to survival benefit 6
• Appropriate surgical margins are 2 mm for DCIS (versus "no tumor on ink" for invasive disease) 1

When RT Can Be Omitted After Lumpectomy

The ONLY scenario where RT can be safely omitted is:

• Age ≥70 years AND
• T1 tumor (≤2 cm) AND
• Node-negative disease AND
• ER-positive tumor AND
• Patient will receive endocrine therapy (tamoxifen or aromatase inhibitor) 1

This is a Category 1 recommendation based on 12.6-year follow-up data showing no difference in overall survival, disease-free survival, or breast cancer-specific mortality, despite 8% higher local recurrence (10% vs 2%) 1

Critical caveat: Even in this low-risk elderly population, RT still significantly reduces locoregional recurrence (HR 0.18), so the decision requires informed patient discussion about accepting higher local recurrence risk in exchange for avoiding treatment 1

Accelerated Partial Breast Irradiation (APBI) as Alternative

APBI may be offered as an alternative to whole-breast RT in highly selected patients meeting ASTRO 2016 "suitable" criteria: 1

• Age ≥50 years (lowered from previous 60 years) AND
• Invasive ductal carcinoma ≤2 cm (T1) AND
• Negative margins ≥2 mm AND
• No lymphovascular invasion AND
• ER-positive AND
• BRCA-negative

OR

• Low/intermediate grade screen-detected DCIS ≤2.5 cm AND
• Negative margins ≥3 mm 1

Absolute Contraindications to RT After Lumpectomy

• Homozygous ATM mutation (absolute contraindication) 1
• Li-Fraumeni syndrome (relative contraindication) 1

After Mastectomy

Clear Indications for Post-Mastectomy RT (PMRT)

PMRT is mandatory for:

• T3-T4 tumors (≥5 cm or chest wall/skin involvement) 1
• Four or more positive axillary lymph nodes 1
• Positive or close surgical margins 1

PMRT should be strongly considered for:

• 1-3 positive axillary lymph nodes, particularly with additional high-risk features (ASCO/ASTRO/SSO joint guidelines recommend individualized approach based on patient preference and risk factors) 1
• Node-negative disease with multiple high-risk features: tumors ≥2 cm, premenopausal status, triple-negative subtype, lymphovascular invasion, or close margins 1

The evidence shows PMRT reduces both recurrence and breast cancer mortality even in patients with 1-3 positive nodes receiving systemic therapy 1

After Neoadjuvant Chemotherapy

• Target volumes should be based on the worst stage (either pre-treatment or post-treatment characteristics) 7
• If pN0 after neoadjuvant chemotherapy and mastectomy, chest wall RT is recommended if there was clinical/radiological T3-T4 or node-positive disease before chemotherapy 3

Regional Nodal Irradiation

Indications for treating regional lymph nodes:

• Any positive axillary nodes warrant supraclavicular and infraclavicular nodal irradiation 1
• Internal mammary node irradiation must be discussed case-by-case, weighing benefit against cardiac toxicity risk 3
• After positive sentinel lymph node biopsy without axillary dissection, extent varies by risk: lowest risk receives no RT, intermediate risk receives level 1-2 RT, highest risk receives full level 1-4 RT including internal mammary nodes 7
• After complete axillary lymph node dissection, the resected axilla should NOT be irradiated unless there is clear residual disease 7

Technical Requirements

• CT-based treatment planning is mandatory across all scenarios to identify and minimize lung and heart exposure 1, 7
• Hypofractionation is NOT generally used in post-mastectomy settings or when treating regional nodes 1