Adjuvant Radiotherapy after Surgical Treatment of Breast Cancer

• Following breast-conserving surgery (lumpectomy, partial mastectomy):
  • 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 (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%
    • 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:
      • Many of them did not receive systemic therapy (36%):
        • 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 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
          • 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:
        • 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 reduces local-regional failure, any recurrence, and 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.
  • Kuerer HM reviewing EBCTCG (Early Breast Cancer Trialists’ Collaborative Group). Postmastectomy radiotherapy for breast cancer patients with one to three positive nodes? NEJM Journal Watch. April 18, 2014. http://www.jwatch.org/na34112/2014/04/18/postmastectomy-radiotherapy-breast-cancer-patients-with. Accessed February 28, 2016.
  • 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.

👉Rodrigo Arrangoiz MS, MD, FACS es cirujano oncólogo experto en mamá y es miembro de la Sociedad Quirúrgica S.C en el Hospital ABC en la Ciudad de México: 


👉Es un experto en el manejo del cáncer de seno. 



👉Si tiene alguna pregunta sobre el examen de detección de cáncer de seno, no dude en comunicarse con el Dr. Arrangoiz.

👉Rodrigo Arrangoiz MS, MD, FACS a surgical oncologist and is a member of Sociedad Quirúrgica S.C at the America British Cowdray Medical Center in Mexico City:

👉He is an expert in the management of breast cancer.

👉If you have any questions about the screening for breast cancer please fill free to contact Dr. Arrangoiz.