In a postmenopausal woman with estrogen‑receptor‑positive (ER+) early‑stage breast cancer who cannot complete a five‑year course of aromatase inhibitor (AI) therapy, is there still a clinical benefit?

Clinical Benefit of Incomplete Aromatase Inhibitor Therapy in Breast Cancer

Yes, there is substantial clinical benefit even if a postmenopausal woman with ER+ early-stage breast cancer cannot complete the full five years of aromatase inhibitor therapy—the benefit accrues primarily during the period when treatment is actually taken, with the greatest reduction in recurrence risk occurring in the first 1-4 years of therapy. 1

Evidence for Time-Dependent Benefit

The most compelling evidence comes from a large patient-level meta-analysis of 31,920 postmenopausal women, which demonstrated that aromatase inhibitors reduce recurrence rates by approximately 30% compared to tamoxifen while treatments differ, but not significantly thereafter 1. This finding has critical implications:

• Years 0-1: Aromatase inhibitors showed the strongest benefit with a recurrence rate ratio of 0.64 (95% CI 0.52-0.78) compared to tamoxifen 1
• Years 2-4: Continued significant benefit with RR 0.80 (95% CI 0.68-0.93) 1
• After treatment cessation: The protective effect diminishes, with non-significant benefit thereafter (RR 0.93,95% CI 0.86-1.01) 1

Minimum Duration Recommendations

The NCCN guidelines explicitly state that adjuvant endocrine therapy is recommended for a minimum of 5 years, but this does not mean shorter durations provide no benefit 2. The evidence structure reveals:

• Even 2-3 years of aromatase inhibitor therapy provides meaningful recurrence reduction during the treatment period 2
• Sequential therapy trials (switching from tamoxifen to AI at 2-3 years) demonstrated significant benefit during the AI treatment period with RR 0.56 (95% CI 0.46-0.67) for years 2-4 1
• The ASCO 2010 guidelines acknowledged that AI therapy duration should not exceed 5 years in the sequential setting, implying that even 2-3 years of AI use (after tamoxifen) confers benefit 2

Mortality Benefit Persists Beyond Treatment Period

Critically, breast cancer mortality reduction continues even after treatment cessation, which is the most important outcome for patients 1:

• 10-year breast cancer mortality was reduced from 14.2% to 12.1% with 5 years of AI versus tamoxifen (RR 0.85,95% CI 0.75-0.96) 1
• Breast cancer mortality was reduced both while treatments differed (RR 0.79,95% CI 0.67-0.92) and subsequently (RR 0.89,95% CI 0.81-0.99) 1
• All-cause mortality was also reduced (RR 0.88,95% CI 0.82-0.94) 1

This suggests that even incomplete AI therapy can reduce the risk of death from breast cancer, as the treatment effects on micrometastatic disease during the treatment period translate into long-term survival benefits.

Risk Stratification for Incomplete Therapy

The benefit of any duration of AI therapy must be weighed against the patient's baseline recurrence risk 2:

• Node-positive disease: Women with node-positive breast cancer derive substantial benefit and should be strongly encouraged to continue AI therapy as long as tolerable, as they have higher absolute risk reduction 2
• High-risk node-negative disease (T2/T3 tumors, high grade): These patients also derive meaningful benefit from any duration of AI therapy 2
• Low-risk node-negative disease (T1a/T1b tumors): The NCCN panel acknowledged that 5 years of AI-containing therapy may be sufficient for these patients, suggesting that shorter durations in this population may still provide adequate benefit 2

Practical Clinical Algorithm

When a patient cannot complete 5 years of AI therapy, the following approach is recommended:

1. Assess duration already completed: Any AI therapy is better than none, with maximal benefit in years 0-4 1

2. Consider switching strategies if intolerable side effects are the issue 3:

   • Switch to a different AI (incomplete cross-resistance between steroidal and non-steroidal AIs) 3
   • Consider sequential therapy with tamoxifen if all AIs are not tolerated 3

3. For patients who must discontinue AI therapy entirely:

   • Reassure them that the benefit accrued during treatment persists for mortality reduction 1
   • The recurrence risk reduction is greatest during the treatment period but mortality benefits extend beyond 1
   • Even 2-3 years of AI therapy provides clinically meaningful benefit compared to no AI therapy 2, 1

Common Pitfalls to Avoid

• Do not tell patients that incomplete therapy provides "no benefit": The evidence clearly shows dose-dependent and time-dependent benefit, with the greatest impact during active treatment 1
• Do not abandon AI therapy without attempting alternative AIs: Switching between agents may allow continuation of therapy 3
• Do not ignore the mortality benefit: Even if recurrence risk increases after stopping therapy, the mortality reduction persists 1
• Do not apply extended therapy data (7-10 years) to the question of incomplete initial therapy: Extended therapy trials showed modest additional benefit beyond 5 years, but this does not negate the substantial benefit of the initial 2-5 years 2, 4

Quantifying the Benefit

For context, 5 years of AI therapy reduces 10-year breast cancer mortality by approximately 15% compared to 5 years of tamoxifen, which itself reduces mortality by about 40% compared to no endocrine therapy 1. Therefore:

• Any duration of AI therapy provides proportional benefit during the treatment period 1
• A patient completing 2-3 years of AI therapy still receives substantial recurrence reduction during those years (RR 0.64-0.80) 1
• The absolute benefit depends on baseline risk, but relative risk reductions remain consistent across risk groups 1