Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) Data on Adjuvant Radiotherapy.

  • Following breast-conserving surgery (BCS):
    • Adjuvant radiotherapy is recommended:
      • Due to benefits in:
        • Local control and 
        • Potentially breast cancer mortality
  • The EBCTCG meta-analysis:
    • Found that for patients undergoing breast-conserving surgery that are N0:
      • Radiation reduced the risk of any recurrence:
        • 16% vs 31% and
      • Reduced breast cancer mortality:
        • 17% vs 21%
  • 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):
        • 4% vs 20% and
      • Reduction in breast cancer mortality:
        • 42% vs 50%
    • Although many have interpreted the EBCTCG findings to mean:
      • All post-mastectomy patients with 1 to 3 positive nodes should have post-mastectomy radiation therapy (PMRT):
        • The patients enrolled in the trials in that meta-analysis were from a different era:
          • And it is 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:
          • And 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, and 
          • 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 EBCTCG meta-analysis who were not treated with PMRT:
          • Had a 20% rate of LRR:
            • 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 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 and 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, 4.1% with intermediate-risk, and 2.4% with low-risk Oncotype DX recurrence scores
  • Additionally, 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 patients younger than age 40 years, tumors larger than 3 cm, and the presence of extensive intraductal components significantly increased the risk of LRR
      • 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 PMR:
    • 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 (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Surgical Oncology (SSO):
    • 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:
        • Reduces local-regional failure
        • Reduces any recurrence
        • Reduces breast cancer mortality:
          • In patients with T1 to T2 breast cancer with 1 to 3 positive lymph nodes
      • They agreed that the decision for PMRT should be made in a multidisciplinary setting and 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
  • References:
    • Early Breast Cancer Trialists’ Collaborative Group, Darby S, McGale P, Correa C, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011;378:1707-1716.
    • Early Breast Cancer Trialists’ Collaborative Group, McGale P, Taylor C, Correa C, et al. Effect of radiotherapy after mastectomy 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.
    • Lai SF, Chen YH, Kuo WH, et al. Locoregional recurrence risk for postmastectomy breast cancer patients with T1-2 and one to three positive lymph nodes receiving modern systemic treatment without radiotherapy. Ann Surg Oncol. 2016;23:3860-3869.
    • Mamounas EP, et al. The 21-gene recurrence score (RS) predicts risk of loco-regional recurrence (LRR) in node (+), ER (+) breast cancer (BC) after adjuvant chemotherapy and tamoxifen: results from NSABP B-28. Presented at: Society of Surgical Oncology Annual Meeting; March 6-9, 2013; National Harbor, MD.
    • Mamounas EP, Tang G, Paik S, et al. The 21-gene recurrence score (RS) predicts risk of loco-regional recurrence (LRR) in node (+), ER (+) breast cancer (BC) after adjuvant chemotherapy and tamoxifen: results from NSABP B-28. Ann Surg Oncol. 2013;20:S6 (Abstract 2).
    • McBride A, Allen P, Woodward W, et al. Locoregional recurrence risk for patients with T1,2 breast cancer with 1-3 positive lymph nodes treated with mastectomy and systemic treatment. Int J Radiat Oncol Biol Phys. 2014;89:392–398.
    • Recht A, Comen EA, Fine RE, et al. Postmastectomy radiotherapy: an American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology focused guideline update. Ann Surg Oncol. 2016. [Epub ahead of print].
    • Sharma R, Bedrosian I, Lucci A, et al. Present-day locoregional control in patients with T1 or T2 breast cancer with 0 or 1 to 3 positive lymph nodes after mastectomy without radiotherapy. Ann Surg Oncol. 2010;17:2899-2908.

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