What is the risk of recurrence in a patient with multifocal invasive lobular carcinoma treated with lumpectomy, radiation therapy, oophorectomy, Femara (letrozole) for 10 years, and Verzenio (abemaciclib) for 2 years, with a history of negative computed tomography (CT) scans for 2 years?

Risk of Recurrence After Comprehensive Treatment for Multifocal Invasive Lobular Carcinoma

Based on this patient's comprehensive treatment regimen including lumpectomy, radiation, oophorectomy, 2 years of Verzenio (abemaciclib), and planned 10-year letrozole therapy, the estimated 4-year invasive disease-free survival is approximately 85.8%, translating to a recurrence risk of approximately 14-15% at 4 years, with ongoing risk extending to 20 years that requires continued surveillance and endocrine therapy. 1, 2

Quantifying the Recurrence Risk

Baseline Risk Factors

• Node-positive disease with 1-3 positive lymph nodes historically carries a 20-year distant recurrence risk of approximately 32% without modern targeted therapy 2
• Multifocal disease (2.2 cm primary plus 3mm satellite lesion) increases the disease burden and baseline recurrence risk beyond unifocal disease 2
• Invasive lobular carcinoma has distinct metastatic patterns and requires long-term vigilance 3

Treatment Impact on Risk Reduction

Abemaciclib benefit: The monarchE trial demonstrated that 2 years of abemaciclib 150 mg twice daily plus endocrine therapy achieved an 85.8% 4-year invasive disease-free survival in high-risk, node-positive, HR+/HER2- breast cancer, compared to 79.4% with endocrine therapy alone (absolute benefit of 6.4%) 1. This represents a 33.6% relative risk reduction (HR 0.664) 1. However, this patient received the reduced 100 mg dose, which may provide somewhat less benefit than the standard 150 mg dose used in the trial 4.

Radiation therapy benefit: Lumpectomy with whole-breast radiation reduces 10-year local recurrence risk and provides a 15-year breast cancer death reduction with a relative risk of 0.52 2. For node-positive disease after lumpectomy, radiation improves 5-year disease-free survival to 89.7% compared to 84.0% without regional nodal radiation 2.

Extended endocrine therapy benefit: The patient's plan for 10 years of letrozole (versus the standard 5 years) provides additional protection against late recurrence, which is critical since hormone receptor-positive breast cancer demonstrates steady recurrence rates extending to 20 years after diagnosis 2, 5. Extended adjuvant letrozole reduces residual risk of recurrence by 42% compared to placebo after completing 5 years of tamoxifen 5.

Critical Ongoing Risk Considerations

The Plateau Effect

• The benefit of abemaciclib plateaus after treatment completion, and residual recurrence risk remains 2
• At 42 months median follow-up in monarchE, the invasive disease-free survival benefit was sustained but not increasing, with 157 deaths (5.6%) in the abemaciclib group versus 173 deaths (6.1%) in the control group 1
• Overall survival data remain immature with no significant improvement yet demonstrated (HR 0.929,95% CI 0.748-1.153; p=0.50) 1

Long-Term Recurrence Pattern

• Hormone receptor-positive breast cancer has a persistent annual recurrence rate that continues for at least 20 years 2, 5
• The patient's negative CT scans for 2 years are reassuring but do not eliminate ongoing risk 2
• Local recurrence typically occurs 3-6 years post-treatment at an average annual rate of 0.5-1% per year with modern therapy 4

Surveillance Strategy

Imaging Recommendations

• Annual diagnostic mammography is mandatory for patients with history of multifocal disease and breast-conserving therapy 4, 2
• Consider 6-month imaging intervals for the first 3-5 years post-treatment for earlier detection of local recurrence, though this does not improve survival compared to annual surveillance 4, 2
• Routine CT surveillance beyond 2 years is not recommended by ASCO and NCCN in asymptomatic patients, as there is no evidence of improved survival 4

Endocrine Therapy Adherence

• Continuation of letrozole for the full 10-year planned duration is critical to address ongoing recurrence risk 2
• Bone health monitoring is essential due to oophorectomy and aromatase inhibitor therapy increasing osteoporosis risk 2

Common Pitfalls to Avoid

• Do not discontinue letrozole prematurely based on negative surveillance imaging, as recurrence risk persists for 20 years 2, 5
• Do not assume the reduced abemaciclib dose (100 mg) provides equivalent benefit to the standard 150 mg dose studied in monarchE 4, 1
• Do not rely solely on CT scans for surveillance, as mammography remains the primary modality for detecting local recurrence 4
• Do not neglect bone density monitoring, as combined oophorectomy and aromatase inhibitor therapy significantly increases fracture risk 2