What are the inclusion and exclusion criteria for the OlympiA trial (olaparib) in adults (≥18 years) with HER2‑negative early‑stage (stage II‑III) breast cancer and a germline BRCA1/BRCA2 pathogenic variant?

OlympiA Trial Inclusion and Exclusion Criteria

Key Inclusion Criteria

The OlympiA trial enrolled adults (≥18 years) with HER2-negative early-stage breast cancer who carried germline BRCA1 or BRCA2 pathogenic/likely pathogenic variants and met specific high-risk clinicopathological criteria after completing standard local treatment and chemotherapy. 1, 2

Disease Characteristics Required

• HER2-negative status (encompassing both hormone receptor-positive and triple-negative subtypes) 3
• Germline BRCA1 or BRCA2 pathogenic or likely pathogenic variant confirmed by genetic testing 1, 2
• High-risk clinicopathological features defined differently by hormone receptor status 1, 3

High-Risk Criteria by Subtype

For Triple-Negative Breast Cancer (TNBC):

• Tumor size ≥2 cm OR any involved axillary lymph nodes 3
• This applies whether patients received neoadjuvant or adjuvant chemotherapy 1

For Hormone Receptor-Positive Disease:

• At least 4 involved axillary lymph nodes 3
• This more stringent criterion reflects the different natural history of HR+ disease 1

Treatment Requirements Before Enrollment

• Completion of at least 6 cycles of (neo)adjuvant chemotherapy 1
• 95% of trial participants received anthracycline and taxane-based chemotherapy, establishing this as the expected standard 1
• Completion of all local treatment including surgery and radiation therapy 1, 3
• Patients must have completed definitive local therapy before starting olaparib 2

Key Exclusion Criteria (Inferred from Trial Design)

While the provided evidence does not explicitly list exclusion criteria, the following can be inferred from the trial design and clinical context:

Disease-Related Exclusions

• HER2-positive breast cancer (trial specifically required HER2-negative status) 1, 2
• Metastatic disease at enrollment (trial focused on early-stage disease) 1, 2
• Absence of germline BRCA1/2 pathogenic variants (somatic mutations alone would not qualify) 1, 2

Treatment-Related Exclusions

• Failure to complete minimum chemotherapy requirements (at least 6 cycles required) 1
• Incomplete local therapy at time of randomization 1, 2

Clinical Context and Real-World Application

Approximately 13-14% of patients with HER2-negative early breast cancer meet the high-risk OlympiA criteria, with substantial variation by subtype: 46.8% of TNBC patients versus only 7.5-9.1% of HR+ patients qualify 4, 5. This translates to roughly 1 in 10 HR+ patients and half of TNBC patients meeting enrollment criteria 5.

Critically, about 44-50% of high-risk patients do not meet traditional hereditary cancer testing criteria based on family history alone, meaning universal BRCA testing is now required for all high-risk HER2-negative early breast cancer patients to identify olaparib candidates 5. This represents a paradigm shift from family history-driven to tumor biology-driven genetic testing 5.

Important Caveats

• The trial did not assess olaparib versus capecitabine in the post-neoadjuvant TNBC setting, leaving uncertainty about optimal sequencing when both agents are indicated 3
• Concurrent use of capecitabine and olaparib is not recommended due to overlapping hematologic toxicity and lack of safety data 6
• For HR+ patients with ≥4 positive nodes, combined use of olaparib (1 year) and abemaciclib (2 years) is permitted per NCCN guidelines, though evidence level is not explicitly graded 3