What are the indications for radiotherapy (radiation therapy) in breast cancer?

Indications for Radiotherapy in Breast Cancer

Radiotherapy is strongly indicated after breast-conserving surgery for invasive breast cancer to reduce local recurrence by two-thirds and improve survival, and after mastectomy for patients with ≥4 positive nodes, T3-T4 tumors, or 1-3 positive nodes with additional risk factors. 1

After Breast-Conserving Surgery (BCS)

Invasive Carcinoma

• Whole breast radiotherapy is mandatory after BCS for invasive cancer (45-50 Gy in 25-28 fractions OR hypofractionated 15-16 fractions with 2.5-2.67 Gy per fraction), as it reduces local recurrence risk by approximately 67% and provides a survival benefit. 2, 1

• Boost irradiation to the tumor bed (10-16 Gy) is strongly indicated for patients with unfavorable risk factors including age <50 years, positive or close margins, lymphovascular invasion, or high-grade tumors, providing an additional 50% reduction in local recurrence risk. 2, 1, 3

• For patients >70 years with endocrine-responsive pT1N0 tumors and clear margins, radiation may potentially be omitted without compromising survival, though this remains controversial. 2

Ductal Carcinoma In Situ (DCIS)

• Whole breast irradiation after BCS for DCIS is strongly recommended as it decreases local recurrence risk, though it does not affect survival. 2

• A boost to the tumor bed should be considered for higher-risk patients, particularly those who are young, though randomized data are lacking. 2

After Mastectomy

Clear Indications (Category 1)

• Post-mastectomy radiotherapy (PMRT) is always recommended for:
  • Patients with ≥4 positive axillary lymph nodes 2, 1
  • T3-T4 tumors (>5 cm or chest wall/skin involvement) independent of nodal status 2, 1

Strong Consideration (Category 2A/2B)

• PMRT should be strongly considered for patients with 1-3 positive axillary nodes, particularly when additional risk factors are present including young age, lymphovascular invasion, low number of examined nodes, or tumors >5 cm. 2, 1

• This recommendation reflects contradictory high-level evidence, with Danish trials showing survival benefit but other studies failing to demonstrate advantage. 2

Node-Negative Disease

• PMRT is recommended for node-negative patients with tumors >5 cm or close/positive margins (<1 mm). 2

• PMRT is not recommended for patients with tumors ≤5 cm, margins ≥1 mm, and no positive nodes. 2

Regional Nodal Irradiation

Supraclavicular and Infraclavicular Nodes

• Strongly recommended (Category 2A) for patients with ≥4 positive nodes after either BCS or mastectomy. 2, 1, 4

• Should be strongly considered (Category 2B) for patients with 1-3 positive nodes, particularly with additional risk factors. 2, 1, 4

• Indicated when there is extensive axillary involvement (N≥2). 2, 1

Internal Mammary Nodes

• Should be included when there is documented metastatic spread to this region or medial/central tumor location with axillary node involvement. 2, 1

• The NCIC-CTG MA.20 trial demonstrated that regional node irradiation (including internal mammary nodes) improves disease-free survival and reduces locoregional and distant recurrence in node-positive patients. 2, 4

• Considerable controversy exists regarding routine internal mammary node irradiation due to potential cardiac toxicity versus uncertain benefit. 2

Special Considerations

After Neoadjuvant Chemotherapy

• Radiation decisions should be based on pre-chemotherapy tumor characteristics, regardless of response to neoadjuvant therapy. 2, 4

• Patients with clinical stage III disease who achieve pathologic complete response still require radiotherapy. 4

Hypofractionation

• Hypofractionated regimens (e.g., 42.5 Gy in 16 fractions or 40 Gy in 15 fractions) are validated alternatives to conventional fractionation with similar effectiveness and toxicity. 2, 1

• Caution is warranted in young patients and those receiving regional nodal irradiation, as these populations were underrepresented in hypofractionation trials. 2

Partial Breast Irradiation

• Should only be used in carefully selected patients ≥50 years with unicentric, unifocal, node-negative, non-lobular cancer ≤3 cm without extensive intraductal component or lymphovascular invasion. 1

• Currently not recommended outside clinical trials for most patients. 2

Technical Considerations

• CT-based treatment planning is mandatory to minimize cardiac and pulmonary radiation exposure, particularly when treating regional nodes. 2, 4

• Standard dose for chest wall/breast: 45-50 Gy in 1.8-2.0 Gy fractions or 42.5 Gy in 2.55 Gy fractions. 2, 1, 4

• Endocrine therapy and trastuzumab can be administered concurrently with radiation therapy. 2