Evaluating the Age-Based Recommendations for Long-Term Follow-Up in Breast Cancer

Abstract

Background: After 5 years of annual follow-up following breast cancer, Dutch guidelines are age based: annual follow-up for women <60 years, 60-75 years biennial, and none for >75 years. We determined how the risk of recurrence corresponds to these consensus-based recommendations and to the risk of primary breast cancer in the general screening population.

Subjects, materials, and methods: Women with early-stage breast cancer in 2003/2005 were selected from the Netherlands Cancer Registry (n = 18,568). Cumulative incidence functions were estimated for follow-up years 5-10 for locoregional recurrences (LRRs) and second primary tumors (SPs). Risks were compared with the screening population without history of breast cancer. Alternative cutoffs for age were determined by log-rank tests.

Results: The cumulative risk for LRR/SP was lower in women <60 years (5.9%, 95% confidence interval [CI] 5.3-6.6) who are under annual follow-up than for women 60-75 (6.3%, 95% CI 5.6-7.1) receiving biennial visits. All risks were higher than the 5-year risk of a primary tumor in the screening population (ranging from 1.4% to 1.9%). Age cutoffs <50, 50-69, and > 69 revealed better risk differentiation and would provide more risk-based schedules. Still, other factors, including systemic treatments, had an even greater impact on recurrence risks.

Conclusion: The current consensus-based recommendations use suboptimal age cutoffs. The proposed alternative cutoffs will lead to a more balanced risk-based follow-up and thereby more efficient allocation of resources. However, more factors should be taken into account for truly individualizing follow-up based on risk for recurrence.

Implications for practice: The current age-based recommendations for breast cancer follow-up after 5 years are suboptimal and do not reflect the actual risk of recurrent disease. This results in situations in which women with higher risks actually receive less follow-up than those with a lower risk of recurrence. Alternative cutoffs could be a start toward risk-based follow-up and thereby more efficient allocation of resources. However, age, or any single risk factor, is not able to capture the risk differences and therefore is not sufficient for determining follow-up. More risk factors should be taken into account for truly individualizing follow-up based on the risk for recurrence.

Keywords: Breast cancer; Locoregional recurrence; Risk-based follow-up; Second primary; Thresholds.

Figure 1

Cumulative incidence functions during 10 years of follow‐up stratified by age. (A): LRR. (B): SP. (C): LRR and SP combined. Abbreviations: FU, follow‐up; LRR, locoregional recurrence; SP, secondary primary tumor.

Figure 2

Cumulative incidence functions with 95% confidence intervals (CIs) for (A) the current age categories during years 5–10 of follow‐up for locoregional recurrence (LRR) and secondary primary tumor (SP) combined, compared with the risk of a primary tumor in the healthy screening population (Δ) having biennial screening, divided in 5‐year age categories, and (B) LRR and SP combined after 5 years of follow‐up using the proposed age cutoffs. Note how the first two risk groups switch: with the proposed cutoffs, the highest risk group (<50) receives annual follow‐up after 5 years and the lower risk group (50–69) biennial follow‐up. Abbreviation: FU, follow‐up.

Figure 3

Examples of risk groups to illustrate the imbalance between the risk and recommendations based on age‐related thresholds. (A): Cumulative incidence of locoregional recurrence (LRR) and secondary primary tumor (SP) combined over 10 years of follow‐up using the proposed age cutoffs after 5 years and the corresponding recommendations. (B): Cumulative incidence of combined LRR and SP of the entire population to determine equally spaced risk intervals per visit, to propose a follow‐up visit only when the risk level is reached (not at set time periods). (C): Cumulative incidence of LRR and SP combined with 95% confidence intervals for two example risk groups based on age (<50) and endocrine therapy (yes/no), showing significant differences in risk within one age group. On the cumulative incidence functions, the risk intervals for the first five visits (as depicted in B) are projected. Based on these simple thresholds, the high risk group might benefit from more frequent visits, as it reaches the risk level of the entire population (visit 5) already after 3 years, whereas it takes around 7 years for the lower risk group. However, these thresholds only take into account the risk and current recommendations, not the benefits and harms. Abbreviation: FU, follow‐up.