BACKGROUND AND PURPOSE:

• 5 year adjuvant endocrine treatment substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer
• Tamoxifen reduces recurrence rates by approximately 50% during the first 5 treatment years and 30% during the next 5 years
• Extended treatment past 5 years is correlated with additional side effects
• Hongchao et al. (NEJM, 2017) sought to determine the impact of various characteristics of the original tumor on the 20-year incidence of breast cancer outcomes among women who received adjuvant endocrine therapy for 5 years
• The main goal of the study was to identify subgroups of women who may be at such low risk for recurrence after stopping endocrine therapy that risks of continuing such therapy would outweigh benefits

METHODS:

• Meta-analysis
  • 88 trials in the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) database of randomized trials
  • Inclusion: Women with ER-positive breast cancer disease-free after 5 years of scheduled endocrine therapy (tamoxifen or aromatase inhibitor)
  • T1 disease (tumor diameter, ≤2.0 cm) or T2 disease (tumor diameter, >2.0 to 5.0 cm)
  • < 10 involved nodes (no nodes [N0]; 1 to 3 nodes [N1–3]; or 4 to 9 nodes [N4–9])
  • No metastases
• Primary outcomes
  • Rate of distant recurrence regardless of any local or contralateral events
  • Rate of any breast-cancer event (distant recurrence, locoregional recurrence, or contralateral new primary tumor)
  • Rate of death from breast cancer

RESULTS:

• 62,923 women in 88 trials were still being followed at 5 years without recurrence or a second cancer
• Breast cancer recurrence continued at a steady rate throughout the study period from 5 to 20 years
• Women with stage T1 disease: Risk of distant recurrence was
  • 13% with no nodal involvement (T1N0)
  • 20% with one to three nodes involved (T1N1–3)
  • 34% with four to nine nodes involved (T1N4–9)
• Women with stage T2 disease, the risk of distant recurrence was
  • 19% with T2N0
  • 26% with T2N1–3
  • 41% with T2N4–9
• TN status was correlated with higher risk of death from breast cancer, but not with higher risk of contralateral breast cancer
• Given the TN status, tumor grade (available in 43,590 patients) and Ki-67 marker status (available in 7692 patients) were of only of moderate independent predictive value for distant recurrence
• Progesterone receptor (in 54,115 patients) and human epidermal growth factor receptor type 2 (HER2) status were not predictive
• During the study period from 5 to 20 years, the absolute risk of distant recurrence among patients with T1N0 breast cancer was 10% for low-grade disease, 13% for moderate-grade disease, and 17% for high-grade disease
• Risks of any recurrence or a contralateral breast cancer were 17% for low-grade disease, 22% for moderate-grade disease and 26% for high-grade disease

CONCLUSION:

• After 5 years of adjuvant endocrine therapy, breast-cancer recurrences continued to occur steadily throughout the study period from 5 to 20 years in women with ER-positive, early-stage breast cancer
• There was a high correlation with TN status and distant recurrence
• Knowledge of risks may guide risk prevention strategies, such as extending endocrine therapy

Learn More – Primary Sources:

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

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