Genetic Ancestry and 21-Gene Oncotype DX Breast Cancer Recurrence Scores

Racial and ethnic breast cancer disparities persist. This may be reflected by differences in Oncotype DX recurrence scores (RS), which are higher for Black women. This study assesses the association between ancestry and RS.

Stage I-III hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with ancestry and RS data were prospectively identified from 2017 to 2021. RS were grouped into low, intermediate, and high categories. Multinomial regression determined the association between ancestry and RS controlling for ancestry and estrogen receptor (ER), progesterone receptor (PR), and HER2 expression.

Of 174 patients, 28 (16.1%) self-identified as non-Hispanic White, 107 (61.5%) self-identified as Hispanic White, 19 (10.9%) self-identified as non-Hispanic Black, and 9 (5.2%) self-identified as Hispanic Black. Ninety-four (54.0%) patients had low RS, 51 (29.3%) had intermediate RS, and 29 (16.7%) had high RS. On multivariable analyses, West African ancestry was associated with increased odds of intermediate (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.00-1.04, p = 0.039) and high (OR 1.03, 95% CI 1.00-1.06, p = 0.022) RS. East Asian ancestry was associated with decreased odds of intermediate RS (OR 0.78, 95% CI 0.60-1.00, p = 0.048). Increasing ER (OR 0.43, 95% CI 0.23-0.82, p = 0.011), PR (OR 0.20, 95% CI 0.11-0.34, p < 0.001), and HER2 (OR 0.24, 95% CI 0.09-0.63, p = 0.004) expression were associated with lower odds of high RS.

Increasing West African ancestry is associated with increased odds of high and intermediate RS, while increasing East Asian ancestry is associated with lower odds of intermediate RS. These findings require validation but suggest ancestry may represent a biological biomarker and that assays guiding adjuvant therapy may require ancestry-based calibration in HR+/HER2- tumors.