What is the optimal adjuvant management for a 47‑year‑old premenopausal woman with high‑risk hormone‑receptor‑positive, HER2‑negative left breast cancer (T3, cN1, grade 3) who has completed neoadjuvant doxorubicin/cyclophosphamide and paclitaxel, surgery, radiation, and is now on adjuvant anastrozole, leuprolide, and abemaciclib?

Optimal Management for High-Risk HR+/HER2- Breast Cancer After Neoadjuvant Therapy

Continue the current regimen of abemaciclib plus anastrozole plus leuprolide for a total of 2 years of abemaciclib therapy, as this patient meets high-risk criteria (T3, N1, grade 3) that warrant adjuvant CDK4/6 inhibition based on the monarchE trial. 1

Risk Stratification Confirms High-Risk Status

This patient definitively meets high-risk criteria through multiple pathways:

• T3 tumor (>5 cm) with 1-3 positive nodes qualifies as high-risk regardless of grade, making her eligible for intensified adjuvant therapy beyond endocrine therapy alone 2, 1
• Grade 3 disease with any nodal involvement (N1) further confirms high-risk classification according to established risk stratification frameworks 3, 2
• High-risk disease is defined as 1-3 positive nodes with either grade 3 histology or tumor size ≥5 cm, and this patient has both features 3, 2, 1

Abemaciclib Duration and Rationale

The current triple-therapy regimen (abemaciclib + anastrozole + leuprolide) should continue for 2 years total of abemaciclib:

• Adjuvant abemaciclib for 2 years combined with endocrine therapy is a Category 1 recommendation for patients with ≥4 positive nodes OR 1-3 positive nodes with either grade 3 disease or tumor ≥5 cm 3, 2
• The monarchE trial demonstrated sustained invasive disease-free survival benefit with 2 years of abemaciclib, showing an absolute 6.4% improvement at 4 years (85.8% vs 79.4%, HR 0.664) 1
• The benefit persists beyond completion of the 2-year treatment period, supporting the full duration rather than early discontinuation 1

Endocrine Therapy Backbone

The combination of anastrozole (aromatase inhibitor) plus leuprolide (ovarian suppression) is appropriate for this premenopausal patient:

• Aromatase inhibitors require mandatory ovarian suppression in premenopausal women; using an AI without adequate ovarian suppression leads to compensatory gonadotropin rise and treatment failure 4
• The combination of ovarian suppression plus aromatase inhibitor is a Category 1 recommendation for premenopausal women with high-risk HR-positive disease 3, 2
• Leuprolide should be continued for at least 2 years, though optimal duration extends to 5 years or longer as part of the overall endocrine therapy strategy 3, 2

Total Endocrine Therapy Duration

After completing 2 years of abemaciclib, continue endocrine therapy (anastrozole + leuprolide) for a total of 5 years:

• For premenopausal patients at high risk (young age, grade 3, lymph node involvement), aromatase inhibitor plus ovarian suppression for 5 years is the evidence-based standard 3, 2
• Extended endocrine therapy beyond 5 years may be considered given the high-risk features, though this decision should be made after completing the initial 5-year course 3

Monitoring and Safety Considerations

Key toxicities to monitor during abemaciclib therapy:

• Neutropenia (19.6% grade 3-4), leukopenia (11.4% grade 3-4), and diarrhea (7.8% grade 3-4) are the most common severe adverse events requiring monitoring 1
• Serious adverse events occurred in 15.5% of patients receiving abemaciclib plus endocrine therapy versus 9.1% with endocrine therapy alone 1
• Bone density monitoring is mandatory for patients on aromatase inhibitors; calcium and vitamin D supplementation should be provided 3, 2

Confirmation of Menopausal Status

Monitor estradiol and FSH/LH levels periodically:

• Menopausal status cannot be reliably determined while receiving ovarian suppression 3
• Chemotherapy-induced amenorrhea does not guarantee permanent menopause; many women retain ovarian function and require continued suppression 4
• If under age 60 and amenorrheic for ≤12 months prior to starting adjuvant endocrine therapy, hormonal monitoring is recommended 3

Critical Pitfalls to Avoid

• Never discontinue abemaciclib before completing 2 years unless toxicity is prohibitive; the sustained benefit depends on full treatment duration 1
• Never use anastrozole without confirmed ovarian suppression in a premenopausal woman; this leads to treatment failure and potential disease progression 4
• Do not stop leuprolide prematurely; ovarian suppression must continue throughout aromatase inhibitor therapy 3, 2, 4
• Do not assume permanent menopause from chemotherapy in a 47-year-old woman; ovarian function may recover, necessitating continued GnRH analog therapy 3, 4