Radiation Therapy After Breast-Conserving Surgery in Women 70 Years of Age and Older: How Wisely Do We Choose?

  • A major goal in treating breast cancer is:
    • Individualization of treatments:
      • To optimize local control and prevent recurrence while minimizing morbidity
  • The widespread adoption of sentinel node biopsy for axillary staging, and the use of genomic testing to decrease chemotherapy utilization in patients with hormonally responsive tumors:
    • Are examples of this approach
  • Despite attempts to minimize morbidity:
    • Radiation therapy (RT) has remained the standard of care for patients undergoing breast-conservation therapy:
      • Based on data from the Early Breast Cancer Trialists’ Cooperative Group meta-analyses:
        • Demonstrating that the reduction in local recurrence associated with the use of RT:
          • Is associated with an improvement in overall survival (OS):
            • However, this difference did not become apparent until 15 years of follow-up and:
              • Was only found in women with a 10% reduction in local recurrence at 5 years
  • In selected older women with small (less than 2 cm), clinically node-negative, estrogen receptor-positive (ER+) tumors undergoing breast-conserving surgery:
    • The omission of adjuvant RT has been proven to be safe in randomized trials with long-term follow-up:
      • While there was a significant difference in local recurrence among patients who did and did not receive adjuvant radiation:
        • This rate was low overall and there was no difference in OS between groups
  • Despite these data, a change in the National Comprehensive Cancer Network (NCCN) guidelines, and the ‘Choosing Wisely’ campaign encouraging cost-effective, thoughtful cancer care:
    • The use of radiation in this population of women remains high nationwide
  • Article:
    • Downs-Canner S, Zabor EC, Wind T, Cobovic A, McCormick B, Morrow M, Heerdt A. Radiation Therapy After Breast-Conserving Surgery in Women 70 Years of Age and Older: How Wisely Do We Choose? Ann Surg Oncol. 2019 Apr;26(4):969-975. doi: 10.1245/s10434-018-07151-4. Epub 2019 Feb 8. PMID: 30737670; PMCID: PMC6613396.
    • Methods: 
      • Women ≥ 70 years of age with T1, ER+, HER2 negative tumors undergoing BCT in 2010 to 2012 were identified from a prospectively maintained database
      • 10-year estimated mortality was calculated using the Suemoto index
      • The associations of clinicopathological features and mortality risk on receipt of RT were examined
    • Results: 
      • 323 patients with 327 cancers were identified
      • Median age was 75 years, median tumor size was 1 cm, and all were clinically node negative
      • 53.7% of patients received RT
      • RT usage decreased with age:
        • 73.6% age 70 to 74
        • 49.5% age 75 to 79
        • 33.3% age 80 to 84
        • 10.7% age > 85
          • (p<0.001)
      • Within age groups, estimated mortality did not impact RT usage
      • On multivariable analysis:
        • Only younger age and larger tumor size were associated with RT use
      • Recurrence-free survival was:
        • 98% versus 93% with and without RT (p=0.011), respectively
      • Those who received adjuvant radiation:
      • Also had improved overall survival (92% versus 89%):
        • Though this effect did not reach statistical significance (p=0.051)
    • Conclusions: 
      • Neither factors associated with risk of local recurrence nor estimated risk of death in 10 years were associated with use of adjuvant radiation in a large cohort of women ≥ 70 years of age with small ER+ breast cancers treated with breast-conserving surgery.
  • Commentary:
    • In these study of women ≥ 70 years of age with small ER+ tumors treated by lumpectomy at an academic medical center:
      • The use of adjuvant radiation was 50% overall and nearly 75% in women age 70 to 75 years:
        • Despite data from randomized controlled trials demonstrating no survival advantage of adjuvant radiation in this population
    • In the CALGB study in women treated with lumpectomy and tamoxifen:
      • The addition of radiation did not change survival with over 10 years of follow-up:
        • 67% versus 66%:
          • Despite a significant difference in locoregional-recurrence-free survival:
            • 98% versus 90% at 10 years
    • Similarly, the PRIME II trial compared patients with tumors up to 3 cm in size and:
      • Showed no difference in overall survival at 5 years:
        • 93.9% in both groups:
          • Despite an absolute difference in ipsilateral breast tumor recurrence of about 3% between groups:
            • 1.3% versus 4.1%
    • Two retrospective studies:
      • Did demonstrate improved survival:
        • When adjuvant radiation was given in conjunction with endocrine therapy in older women:
          • However, the propensity matching performed:
            • Does not eliminate the selection biases inherent in retrospective reviews, and their findings should not challenge the results of the prospective randomized trials
    • In fact, a meta-analysis of over 2300 patients, including the 2 randomized studies, showed that while the addition of radiation to tamoxifen reduced local recurrence from 60 to 10 per 1000 patients at 10 years follow-up, and reduced axillary recurrence from 12 to 3 per 1000 at 5 years15, there was no difference in distant recurrence or overall survival.

#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncologist #BreastCancer

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