Radiotherapy

This is standard treatment for invasive breast cancer following breast conserving surgery (BCS).

If there are contraindications for radiotherapy, inability to achieve the RT position or a gene mutation, the patient may ultimately proceed to a mastectomy, after discussion at MDM and with the patient.

PBI can be used in lower risk patients with indications as per IMPORT LOW trial (1)

All the following indications must be present to be eligible for PBI:

• >50yrs
• <30mm
• Grade 1/2
• Node negative
• ER 7-8/HER2 negative
• Clear margins
• Unifocal disease
• Non lobular pathology
• No lymphovascular invasion (LVI)

RT can be omitted in low risk older patients after discussion with them regarding higher local recurrence rate without RT (2)

All the following indications must be present for the patient to be eligible for omission of RT:

• ≥70yrs
• ≤20mm 
• Node negative
• Grade1/2
• ER 7/8
• HER2negative
• Without extensive HG DCIS

Patients are recommended to take endocrine therapy for at least 5 years if not receiving RT

Indications (3) :

• T3 and T4 disease at diagnosis
• ≥4 nodes in axillary node clearance (ANC)
• Margins<1mm
• Consider in patients with 1-3 nodes positive in ANC with at least one other high risk feature:
  • Grade 3
  • LVI positive
  • ER negative
  • HER2 positive

Indications:

• Following breast conserving surgery (BCS) for high grade DCIS
• Patients >65yrs may not benefit from RT and should be discussed at MDM and/or with patient
• Consider RT for IG DCIS following BCS if disease is extensive in a young patient
• Following mastectomy, consider RT for high grade DCIS more than 50mm, or involved margins.

Indications:

• Node positive on sentinel node biopsy (SNB) unless proceeding to ANC
• Known macroscopic disease left in axilla
• Post neoadjuvant chemotherapy with negative SNB if pretreatment diagnostic lymph node biopsy was positive
• No RT is required for isolated tumour cells (ITC) or micrometastases found on SNB if pre-operatively clinically N0 (4)
• Post neoadjuvant chemotherapy: with negative SNB if pretreatment diagnostic lymph node biopsy was positive 
• Post neoadjuvant chemotherapy: with negative SNB and cN0 pre-NAC, but pathological features of previous involvement with cancer in one or more nodes 
  Consider omitting axillary RT if 1 out of at least 2 SLNs shows fibrosis post-NACT and baseline axillary imaging excludes macroscopic axillary disease 

Indications:

• ≥4 nodes positive after axillary node clearance (ANC)
• 1-3 nodes positive after ANC with at least one other high risk feature:
  • Grade 3
  • LVI positive
  • ER negative
  • HER2 positive
• 1-3 nodes positive after ANC in patients who have received neoadjuvant chemo 

IMC RT should be considered in patients at high risk of loco-regional recurrence with the following indications (5-7):

• T4 disease
• N2-3 nodal disease
• N1 with medial/central tumour location
• Radiologically involved IMC nodes at diagnosis

IMC RT should be given using DIBH.

Indications following breast conserving radiotherapy:

• < 50 yrs
• ≥50yrs, consider in patients with higher risk disease eg Grade 3
• T4 disease at presentation if had skin involvement on post-op pathology 
• Transected margins with ink on tumour

Other indications may be considered for boost radiotherapy if there are concerns of increased local recurrence.

A boost can be given sequentially or as a simultaneous integrated boost (SIB)

• 26Gy/5# is the standard dose for breast/chest wall radiotherapy for invasive disease, DCIS and PBI (8)

  40.05Gy/15# can be considered for autologous or implant-based chest wall reconstruction RT

• 40.05Gy/15# is the standard dose for radiotherapy involving any of the nodal regions (axillary levels I-IV +/-IMC)

• Boost dose:

Sequential boost: 10-13.5Gy/4-5# (or BED of 16Gy/8#)

Simultaneous integrated boost (SIB): 48Gy/15# (9)

1. Charlotte E Coles, Clare L Griffin, Anna M Kirby et al. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial). Lancet 2017; 390: 1048–60
2. Kunkler IH, Williams LJ, Jack WJ et al. Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial. Lancet Oncol. 2015; 16: 266-273
3. McGale P, Taylor C, Correa C, et al. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet 2014; 383:2127–2135
4. Viviana Galimberti1, Bernard F Cole  et al. Axillary dissection versus no axillary dissection in patients with breast cancer and sentinel-node micrometastases (IBCSG 23-01): 10-year follow-up of a randomised, controlled phase 3 trial. Lancet Oncology 2018 Oct;19(10):1385-1393
5. Timothy J. Whelan, Ivo A. Olivotto, Wendy R. Parulekar et al. Regional Nodal Irradiation in Early-Stage Breast Cancer. N Engl J Med 2015; 373:307-316
6. Philip M. Poortmans, Sandra Collette, Carine Kirkove et al. Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer. N Engl J Med 2015; 373:317-327
7. Lise Thorsen, Birgitte Vrou Offersen, Hella Danø et al. DBCG-IMN: A Population-Based Cohort Study on the Effect of Internal Mammary Node Irradiation in Early Node-Positive Breast Cancer.  Journal of Clinical Oncology 2016 34:4, 314-320
8. Adrian Murray Brunt, Joanne S Haviland, Duncan A Wheatley et al Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial  Lancet 2020 May 23; 395(10237): 1613–1626.
9. CE Coles,CL Griffin, AM Kirby, et al. Dose escalated simultaneous integrated boost radiotherapy for women treated by breast conservation surgery for early breast cancer: 3-year adverse effects in the IMPORT HIGH trial. AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS4-05