Abstract P6-01-25: Evaluation of Multigene Assays as Predictors for Response to Neoadjuvant Chemotherapy in Early-Stage Breast Cancer Patients

Abstract

Abstract Background: Oncotype DX (ODX) and MammaPrint (MP) are gene-expression assays that have been established to predict distant cancer recurrence in the adjuvant chemotherapy setting. However, they have not been validated to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT). We sought to examine the ability of the ODX and MP assays to predict the likelihood of pCR to NACT in early-stage breast cancer patients. Methods: Data from breast cancer patients diagnosed between 2010 and 2019 were obtained from the National Cancer Database. All patients who received NACT (at least 30 days of treatment) and had pathologic response data and ODX or MP results were included. Analysis of ODX was limited to patients with hormone receptor (HR)+/HER2- stage I-III disease, while analysis of MP included both HR+/HER2- and HR-/HER2- stage I-III patients. ODX scores were modeled both as a continuous variable and a categorical variable classified as low (0-25) and high (≥26) per the TAILORx trial cutoff, whereas MP results were modeled as a dichotomous variable (i.e., low risk and high risk) because numeric values were unavailable. Multivariable logistic regression models were used to assess the relationship between pCR (defined as ypT0/Tis ypN0) and ODX or MP results, adjusting for age, race/ethnicity, clinical T and N stages, tumor grade, and progesterone receptor status. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were calculated. Results: A total of 2,219 patients, treated at 630 institutions, who received NACT with an ODX recurrence score were included in the ODX cohort. Of 1,181 patients with a high ODX score, 11.2% achieved pCR, while only 1.6% of 867 patients with a low ODX score did. In the adjusted model, having a high ODX score was associated with greater odds of pCR (AOR = 4.48, 95% CI: 2.44-8.22). There was a significant monotonic increasing trend of pCR by continuous ODX score. The mean ODX score was 42.5 (SD = 15.5) in patients who achieved pCR, compared to 27.9 (SD = 13.7) in patients who did not; the discriminating capacity of ODX was moderate to strong (area under the ROC curve = 0.767). A total of 1,349 patients, treated at 337 institutions, who received NACT and had MP test results were included in the MP cohort. Of 1,141 patients with MP high risk disease, 11.8% achieved pCR, compared to < 4.8% of 208 patients with MP low risk disease. In the adjusted model, having MP high risk disease was associated with greater odds of pCR (AOR = 2.21, 95% CI: 1.02-4.77). A similar association between MP results and pCR was also found in the subset of patients who were HR+/HER2- (AOR = 2.25, 95% CI: 0.99-5.15). Conclusions: Both ODX and MP were independently associated with likelihood of pCR after NACT for early-stage, high-risk breast cancer. These findings suggest a potential role for ODX or MP testing as a predictive biomarker in the NACT setting, and can facilitate clinical decision making between physicians and patients. Citation Format: Jincong Q. Freeman, Sarah Shubeck, Frederick M. Howard, Nan Chen, Rita Nanda, Dezheng Huo. Evaluation of Multigene Assays as Predictors for Response to Neoadjuvant Chemotherapy in Early-Stage Breast Cancer Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-25.