Abstract P6-01-43: Predictors of Response to Neoadjuvant Chemotherapy in Breast Cancer: OncotypeDX versus MammaPrint versus Liquid Biopsy
Authors: Bilani Nadeem , Itani Mira , Mohanna Mohamed , Debnath Neha , Dominguez Barbara , Liang Hong , Nahleh Zeina 
Published: March 2023

Background: OncotypeDX (ODX) is a 21-gene recurrence score (RS) assay that is predictive of the benefit of adjuvant chemotherapy in early-stage hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer. MammaPrint (MP) is a 70-gene signature validated to prognosticate distant metastasis and survival. We have previously presented data suggesting that the presence of circulating tumor cells (CTCs) evaluated via liquid biopsy may also have prognostic and predictive utility in HR+/HER2- breast cancer. In this study, we compare the value of ODX, MP and liquid biopsy evaluating CTCs and disseminated tumor cells (DTCs) in predicting pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC). Methods: This retrospective analysis used the National Cancer Database (NCDB) 2004-2017 breast cancer dataset to identify a cohort of patients with HR+/HER2-, AJCC clinical stage I-III breast cancer who received NAC. A series of multiple logistic regression models were used to assess the value of a. ODX (RS &lt; 26 versus ≥26), b. MP, c. the presence of CTCs, and d. the presence of DTCs in predicting pCR to NAC. Each model controlled for age, race, Charlson/Deyo comorbidity scoring, disease histology, grade, and nodal status. Results: A total of n=52,463 patients with stages I-III HR+/HER2- breast cancer received NAC. The patient characteristics of this cohort were as follows: the majority were White (n=42,826, 81.6%), between 50-70 years of age (n=27,683, 52.8%), and with invasive ductal carcinomas of the breast (n=40,197, 76.6%). N=6,111 (11.6%) had Grade I or well-differentiated disease, n=23,546 (44.9%) Grade II or moderately-differentiated disease, and n=2,605 (43.5%) had Grade III or poorly-differentiated disease. N=3,823 have documented recurrence scores based on ODX: with n=2,653 having RS &lt; 26 (69.4%) and n=1,170 (30.6%) having RS ≥26. After controlling for age, race, comorbidity scoring, disease histology, grade and nodal status, RS ≥26 was found to be significantly associated with pCR to NAC (OR 1.85, 95% CI 1.46-2.35, p&lt; 0.001). High-risk scoring per MP was also correlated with pCR but this relationship was not statistically-significant (OR 1.68, 95% CI 0.93-3.03, p=0.084), possibly due to the smaller size of this sample (n=828 patients underwent MP testing). Liquid biopsy data was also limited, with n=250 patients having documented CTC status and n=211 having documented DTC status. Neither the presence of CTCs (OR 0.96, 95% CI 0.44-2.09, p=0.908) nor DTCs (OR 0.61, 95% CI 0.25-1.50, p=0.279) was significantly associated with pCR to NAC. Conclusions: ODX is found to be predictive of pCR to NAC in early-stage, HR+/HER2- breast cancer. Utility of MP and liquid biopsy data in this context appears less robust, however, data is limited. More research is needed to validate existing data in a prospective trial setting, and explore for novel biomarkers across breast cancer subtypes.

Citation Format: Nadeem Bilani, Mira Itani, Mohamed Mohanna, Neha Debnath, Barbara Dominguez, Hong Liang, Zeina Nahleh. Predictors of Response to Neoadjuvant Chemotherapy in Breast Cancer: OncotypeDX versus MammaPrint versus Liquid Biopsy [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 P6-01-43.