Breast Cancer with Low Recurrence Score on Oncotype DX^©: Interplay Between Early Recurrence, Lobular Histology and...

Area of Science:

• Oncology
• Genetics
• Breast Cancer Research

Background:

• The 21-gene recurrence score (RS) assay, Oncotype DX (ODX), is established for predicting adjuvant chemotherapy response in early breast cancer (EBC).
• Emerging evidence highlights distinct clinical behaviors of BRCA1/2-mutated EBC and invasive lobular carcinoma (ILC).
• The prognostic utility of ODX in these specific subgroups warrants further investigation.

Purpose of the Study:

• To evaluate the association between BRCA1/2 mutations, ILC, and Oncotype DX failure in patients with a recurrence score ≤20.
• To assess if a low RS accurately reflects a low risk of recurrence in these distinct EBC populations.

Main Methods:

• Retrospective analysis of a small cohort (n=16) of patients experiencing early recurrence despite an ODX RS ≤20.
• Comparison of clinical parameters with a cohort from the general population (Clalit Health Service).
• Assessment of BRCA mutational status and tumor histology (ILC) within the study cohort.

Main Results:

• The study cohort presented with a significantly younger median age at diagnosis.
• A substantial proportion of patients (35.7%) carried BRCA1/2 mutations (germline or somatic).
• Lobular carcinoma (ILC) was diagnosed in 50% of patients, a significantly higher rate than the general population (10-15%).
• The median time to recurrence was 44 months.

Conclusions:

• BRCA1/2 mutations and ILC were highly prevalent in the cohort experiencing early recurrence.
• These findings suggest that an ODX RS ≤20 may not reliably indicate a low risk of recurrence in patients with BRCA1/2 mutations or ILC.
• Further research with larger cohorts is needed to confirm these observations and refine risk stratification strategies.