According to the OLYMPIA trial, what is the recommended adjuvant olaparib regimen (dose, duration, monitoring, and alternatives if contraindicated) for early‑stage high‑risk HER2‑negative breast cancer patients with a germline BRCA1 or BRCA2 pathogenic variant who have completed surgery, radiation, and anthracycline‑taxane‑based chemotherapy (and endocrine therapy if hormone‑receptor‑positive)?

Adjuvant Olaparib Regimen for High-Risk HER2-Negative Breast Cancer with Germline BRCA1/2 Mutations

Administer olaparib 300 mg orally twice daily for 1 year after completing all local treatments including radiation therapy. 1, 2

Dosing and Administration

• Standard dose: Olaparib 300 mg orally twice daily (600 mg total daily dose) 1, 2
• Duration: Continue for exactly 1 year 3, 1, 2
• Timing: Start after completion of all local treatments, including radiation therapy, and after completion of (neo)adjuvant chemotherapy 1, 2
• Endocrine therapy: For hormone receptor-positive disease, olaparib is given concurrently with ongoing endocrine therapy 3

Patient Eligibility Criteria

The OlympiA trial established specific high-risk criteria that determine eligibility: 1

For triple-negative breast cancer (TNBC):

• Tumor size ≥2 cm OR any involved axillary lymph nodes 1
• Applies to all high-risk patients including those with pathologic complete response (pCR) who had initially locally advanced disease 1

For hormone receptor-positive disease:

• At least 4 involved axillary lymph nodes 1

Both subtypes require:

• Germline BRCA1 or BRCA2 pathogenic variant 3, 1
• HER2-negative status 1
• Completion of (neo)adjuvant chemotherapy 1

Monitoring Requirements

Hematologic surveillance is critical:

• Monitor complete blood counts regularly throughout treatment 2
• Watch specifically for grade 3/4 anemia, neutropenia, and thrombocytopenia 2
• These are the most common serious adverse effects requiring dose modification 2

Long-term surveillance:

• Follow patients for myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML), as PARP inhibitors are DNA-interacting drugs with potential to induce hematologic malignancies 1

Important Clinical Considerations

Do not combine with capecitabine:

• Olaparib and capecitabine should NOT be given concurrently due to insufficient safety data, no established clinical benefit, and overlapping hematologic toxicity 2
• For patients with germline BRCA1/2 mutations and residual disease after neoadjuvant chemotherapy, prioritize olaparib as the Category 1 evidence-based choice 2

Sequencing with other adjuvant therapies:

• For HR-positive disease with ≥4 positive nodes, patients may be candidates for both abemaciclib (2 years) and olaparib (1 year) if they have germline BRCA1/2 mutations 3
• The integration of olaparib with pembrolizumab (for TNBC) or abemaciclib (for HR-positive disease) lacks direct comparative data, requiring clinical judgment based on individual risk-benefit assessment 4

Alternatives if Olaparib is Contraindicated

For TNBC with residual disease after neoadjuvant chemotherapy:

• Capecitabine is the alternative if germline BRCA1/2 mutation is absent or if olaparib is contraindicated 2
• Capecitabine is indicated specifically for TNBC with residual disease after taxane-, alkylator-, and anthracycline-based preoperative chemotherapy 2

For HR-positive disease:

• Continue standard endocrine therapy with or without ovarian suppression (for premenopausal patients) 3
• Consider 2 years of abemaciclib if high-risk criteria are met (≥4 positive nodes or 1-3 positive nodes with additional high-risk features) 3

Clinical Outcomes from OlympiA

The trial demonstrated substantial benefit: 1, 2

• 3-year invasive disease-free survival: 85.9% (olaparib) vs 77.1% (placebo), HR 0.58, P<0.001 1, 2
• 3-year distant disease-free survival: 87.5% (olaparib) vs 80.4% (placebo), HR 0.57, P<0.001 1
• 4-year overall survival: 89.8% (olaparib) vs 86.4% (placebo) 3

Common Pitfalls to Avoid

• Do not delay olaparib initiation: Start immediately after radiation completion, not months later 1, 2
• Do not skip BRCA testing in high-risk patients: Approximately half of high-risk patients do not meet traditional hereditary cancer testing criteria based on family history alone, yet may still carry germline BRCA1/2 mutations 5
• Do not withhold olaparib from patients who achieved pCR: The germline BRCA mutation confers inherent genomic instability that justifies adjuvant olaparib even with pCR 1
• Do not use routine imaging for metastatic surveillance: This does not improve survival in asymptomatic patients 6