Chemosensitivity to doxorubicin of ER-positive/HER2-negative breast cancers with high 21-gene recurrence score: A study based on in vitro chemoresponse assay

AIM The 21-gene recurrence score (RS) predicts a clinical benefit of chemotherapy for individuals with ER-positive/HER2-negative breast cancer. Using in vitro chemoresponse assay, we compared the chemosensitivity according to RS in these patients. METHOD Among the patients with Oncotype Dx assay, we identified 63 patients who had chemotherapy response assays to doxorubicin based on adenosine triphosphate. The degree of chemosensitivity to doxorubicin was translated into the cell death rate (CDR). The RS was also dichotomized with a cutoff of 26. RESULTS Of 63 patients, 34 (54%), 17 (27%), and 12 patients (19%) had a low, intermediate, and high RS, respectively. The mean CDR differed significantly according to categorized RS, with 17.3±10.8 in the low RS group vs. 23.6±16.3 in the intermediate RS group vs. 28.8±12.6 in the high RS group (P = 0.024, One-way ANOVA test). The mean CDR was significantly higher in the higher RS (26≥) group compared with the lower RS (<26) group (P = 0.025, the Student's t-test), as well as in the high RS (>30) group compared with the low RS (<18) group (P = 0.012, the Student's t-test). Also, continuous RS and CDR correlated positively (Pearson's R = 0.337; P = 0.007). High RS demonstrated the odds ratio (OR = 26.33; 95% CI = 1.69-410.0) for predicting tumors with chemosensitivity on the multivariate analysis. CONCLUSIONS The chemosensitivity measured by in vitro chemoresponse assay was different according to the RS. Our findings support that tumors with high RS has the chemosensitivity even though they are luminal/HER2-negative tumors.