What is the risk of recurrence for a patient who completed 2 years of Verzenio (abemaciclib) at 100mg, had negative Signatera (circulating tumor cell) monitoring results, and two negative FES (Fluoroestradiol) PET scans?

Risk of Recurrence After Completing 2 Years of Adjuvant Abemaciclib

This patient has an excellent prognosis with a very low risk of recurrence, given completion of 2 years of abemaciclib at 100mg, negative Signatera ctDNA monitoring, and two negative FES PET scans—all indicators suggesting minimal residual disease burden and maintained endocrine sensitivity.

Baseline Risk Reduction from Abemaciclib Therapy

The monarchE trial demonstrated that abemaciclib combined with endocrine therapy significantly reduces recurrence risk in high-risk, HR+/HER2- early breast cancer 1, 2, 3:

• 2-year invasive disease-free survival (IDFS) rates: 92.2% with abemaciclib plus endocrine therapy versus 88.7% with endocrine therapy alone 3
• Hazard ratio for IDFS: 0.75 (95% CI: 0.60-0.93), representing a 25% reduction in recurrence risk 3
• In the Ki-67 ≥20% subgroup (the FDA-approved population), the hazard ratio was even more favorable at 0.643 (95% CI: 0.475-0.872) 2

Your patient completed the full 2-year course at 100mg twice daily, which is the reduced but still therapeutic dose used in the monarchE trial for patients requiring dose modification 1, 2.

Additional Favorable Prognostic Indicators

Negative Signatera Monitoring

• Circulating tumor DNA (ctDNA) negativity throughout surveillance indicates absence of minimal residual disease
• While Signatera data is not specifically referenced in the provided evidence for breast cancer, ctDNA monitoring has emerged as a highly sensitive marker for detecting subclinical recurrence
• Persistent ctDNA negativity correlates with sustained disease-free survival across multiple cancer types

Two Negative FES PET Scans

The negative FES PET scans provide critical reassurance about both disease status and endocrine sensitivity 4, 5:

• FES PET detects ER-positive lesions throughout the body, allowing whole-body assessment of ER functionality 4
• The Society of Nuclear Medicine and Molecular Imaging identifies FES PET as most appropriate for assessing ER status when endocrine therapy is considered or after disease progression 4
• Absence of FES-avid lesions indicates no detectable ER-positive disease and suggests maintained endocrine sensitivity if disease were present 5
• In the metastatic setting, patients with only FES-positive lesions (no FES-negative sites) had median PFS of 23.6 months on CDK4/6 inhibitor therapy, while those with FES-negative sites had median PFS of only 2.4 months 5

Quantifying Current Recurrence Risk

Based on the monarchE data and your patient's favorable surveillance findings:

• Baseline 2-year IDFS with abemaciclib: 92.2% 3
• This translates to approximately 7-8% risk of recurrence within the first 2 years for the overall high-risk population
• Your patient has now completed the 2-year treatment window with negative surveillance, placing her in a more favorable subset
• The negative ctDNA and FES PET findings suggest she falls into the group that achieved complete response to therapy

Estimated ongoing annual recurrence risk: Likely 2-5% per year for years 3-5, then declining further, based on the natural history of HR+/HER2- breast cancer after successful adjuvant therapy 6.

Clinical Implications and Ongoing Management

Surveillance Strategy

Continue routine surveillance per standard guidelines for high-risk early breast cancer 6:

• Physical examination: Every 3-6 months for years 3-5, then annually 6
• Annual mammography: To detect ipsilateral or contralateral breast events 6
• Symptom-directed imaging: Reserve advanced imaging (CT, PET) for symptomatic concerns or clinical findings 6, 7
• Routine surveillance PET is not recommended in asymptomatic breast cancer survivors, as there is no survival benefit from early detection of asymptomatic metastases 7

Continued Endocrine Therapy

• Ensure completion of 5-10 years total endocrine therapy (including the 2 years concurrent with abemaciclib)
• The benefit of abemaciclib was in addition to standard endocrine therapy, which should continue per guidelines 1, 2

Metabolic Risk Factor Management

Breast cancer survivors with metabolic syndrome have 83% higher breast cancer mortality and 69% higher recurrence risk 7:

• Screen for and optimize management of hypertension, diabetes, dyslipidemia, and obesity 7
• Early intervention in metabolic risk factors improves quality of life and overall survival 7

Key Caveats

• Receptor status can change: If recurrence occurs, obtain ER, PR, HER2, and proliferation markers on any metastatic tissue, as receptor status changes from the primary tumor in 20-30% of cases 7
• Late recurrences occur: HR+ breast cancer can recur beyond 5 years, necessitating long-term vigilance 6
• Maintain clinical follow-up: Most recurrences are detected by symptoms or physical examination findings rather than routine imaging 6