Who Should Receive Radiation Therapy Following Breast Cancer Surgery

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Following breast-conserving surgery (partial mastectomy, lumpectomy):
- Adjuvant radiotherapy is recommended due to benefits in:
  - Local control
  - Potentially breast cancer mortality.
The Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) meta-analysis:
- Found that for patients undergoing breast-conserving surgery that are N0:
  - Radiation reduced:
    - The risk of any recurrence:
      - From 31% to 16%
    - Reduced breast cancer mortality:
      - From 21% to 17%
- The EBCTCG also found that for patients undergoing mastectomy with 1 to 3 positive nodes:
  - Radiotherapy was associated with a:
    - Reduction in locoregional recurrence (LRR):
      - From 20% to 4%
    - Reduction in breast cancer mortality:
      - From 50% to 42%
- Although many have interpreted the EBCTCG findings to mean:
  - All postmastectomy patients with 1 to 3 positive nodes should have postmastectomy radiation therapy (PMRT):
    - The patients enrolled in the trials in that meta-analysis were from a different era:
      - Making it difficult to know how relevant the findings are to patients who are diagnosed and treated by current standards:
        
        The patients were enrolled between 1964 and 1986
        
        Many of them did not receive systemic therapy:
        
        The 64% who received chemotherapy were treated with:
        
        Cyclophosphamide, methotrexate, and fluorouracil:
        
        Which is inferior to modern regimens
        
        Only 24% of patients were treated with tamoxifen
        
        No patients received an aromatase inhibitor.
  - The benefit of PMRT diminishes:
    - As the risk of LRR diminishes
  - Patients with 1 to 3 positive nodes in the meta-analysis who were not treated with PMRT:
    - Had a 20% rate of LRR (vs. 4%):
      - But recurrence is significantly lower with modern systemic treatment:
        
        Sharma et al. retrospectively reviewed patients:
        
        Who had mastectomies between 1997 and 2002 and did not receive PMRT:
        
        The 10-year rate of LRR in patients with 1 to 3 positive nodes:
        
        Was only 4.3%:
        
        Compared to 20% in the EBCTCG meta-analysis
        
        Another study of patients with 1 to 3 positive nodes:
        
        Compared the risk of LRR:
        
        Between two different eras, before and after the routine use of sentinel node biopsy, taxane therapy, and aromatase inhibitors:
        
        Use of PMRT reduced the 15-year rate of LRR in the first era:
        
        From 14.5% to 6.1%
        
        PMRT did not appear to benefit patients treated in the second era:
        
        With 5-year LRR rates of:
        
        2.8% without PMRT
        
        4.2% with PMRT
        
        The NSABP B-28 study:
        
        Randomized node-positive patients to:
        
        Doxorubicin and cyclophosphamide versus doxorubicin and cyclophosphamide plus paclitaxel
        
        Use of PMRT was not allowed in patients who were treated with mastectomy:
        
        So the trial gives a good view of the risk of LRR for node-positive patients who are treated with mastectomy and relatively modern systemic therapy.
        
        For patients with 1 to 3 positive nodes:
        
        LRR at 10 years was:
        
        6% for patients with high-risk oncotype DX recurrence scores
        
        4.1% with intermediate-risk oncotype DX recurrence scores
        
        2.4% with low-risk oncotype DX recurrence scores
        
        Lai et al. recently reviewed 293 mastectomy patients with T1 to T2 breast cancer and 1 to 3 positive lymph nodes:
        
        All received anthracycline or taxane based chemotherapy and none received PMRT.
        
        After stratifying patients according to:
        
        Luminal A and B, luminal HER2, HER2, and triple-negative subtypes:
        
        They found patients with triple-negative breast cancer to have the highest 5-year LRR when compared to all other subtypes:
        
        10.6% vs 4.2%:
        
        P=0.05
        
        Multivariate analysis found that the following factors significantly increased the risk of LRR:
        
        Patients younger than age 40 years
        
        Tumors larger than 3 cm
        
        The presence of extensive intraductal components .
        
        The authors concluded that:
        
        Administering modern systemic therapy to early breast cancer patients not receiving PMRT:
        
        Significantly reduces the rate of LRR.
      - In view of the fact that PMRT significantly increased overall mortality in node-negative patients in the EBCTCG (47.6% vs 41.6%; rate ratio 1.23):
        
        Caution should be taken in extrapolating the results to all patients with 1 to 3 positive nodes in the modern era.
  - The American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology:
    - Recently released an updated consensus statement regarding the role of PMRT in women with 1 to 3 positive lymph nodes:
      - The consensus panel unanimously agreed that PMRT in this subset of patients (with T1 to T2 breast cancer with 1 to 3 positive lymph nodes):
        
        Reduces local-regional failure
        
        Any recurrence
        
        Breast cancer mortality in patients.
      - They agreed that the decision for PMRT:
        
        Should be made in a multidisciplinary setting
        
        With the involvement of the patient and her wishes after she is presented with all available data.
      - The panel went on to acknowledge that in some subsets of patients:
        
        The risk of local-regional failure may be so low that the:
        
        Absolute benefit of PMRT is outweighed by its toxicities.
      - Further, even if axillary lymph node dissection is omitted in the setting of a positive lymph node:
        
        PMRT should only be used if there is already significant evidence justifying the benefit of PMRT without knowing the status of any additional axillary nodes.
      - When given:
        
        PMRT should include the:
        
        Internal mammary, supraclavicular, and apical axillary nodes and the chest wall or reconstructed breast.
      - All patients with a positive axillary node after receipt of neoadjuvant chemotherapy should receive PMRT