Abstract 2175: Gene signature predicts pathological complete response in triple negative breast cancer patients: NACATRINE trial
Authors: Freitas Ana J. , Nunes Caroline R. , Causin Rhafaela L. , Santana Iara V. , Oliveira Marco A. , Calfa Stéphanie , Souza Cristiano P. , Marques Márcia M. 
Published: April 2023

In triple negative breast cancer (TNBC), achieving pathological complete response (pCR) is associated with improved survival outcomes. However, only one-third of patients receiving neoadjuvant chemotherapy (NAC) achieve pCR. Recognizing molecular markers that predict response to chemotherapy and selecting patients who can benefit from NAC in clinical practice has been a challenge in many studies. This exploratory analysis of the NACATRINE trial aimed to identify biomarkers that predict pCR TNBC patients receiving NAC.

The NACATRINE trial is a Brazilian, phase II, single-center, randomized, open-label study that compared adding carboplatin to sequential neoadjuvant therapy based on anthracycline and taxane for TNBC. We evaluated gene expression in untreated samples to associate with the response to systemic therapy. RNA was extracted from the tissue biopsy, and the nCounter Breast Cancer panel analyzed gene expression. Gene counts were normalized by housekeeping. For statistical significance, the t-test was used with a p-value &lt;0.05 and fold-change ≥2.

Of the 66 patients included in the gene expression profile analysis, 24 (36.4%) had pCR, and 42 (63.6%) had residual disease. Thirty-seven genes were differentially expressed when associated with pCR in the carboplatin arm and twenty-seven in the non-carboplatin arm (p-value &lt;0.001). We performed a linear regression model to evaluate gene performance, and the area under the curve (AUC) was calculated to assess the predictive value of differentially expressed genes. Eleven genes (KCNB1, FGF1, SNAI1, CXCL9, FGL2, HAS1, CXCL8, VEGFD, HEMK1, MS4A2, and NFKBIZ) in the carboplatin arm (AUC 0.938) and eight genes (ALDH1A1, FZD8, HIST1H3H, CXADR, WDR77, PRKACB, JUN, and CDK6) in the non-carboplatin arm (AUC 0.943) was associated with pCR. Overall survival (OS) was higher among patients who had downregulated KCNB1, FGF1, and SNAI1 (HR = 4.43, 95% CI 1.00 - 1.58; p=0.04; HR = 4.92, 95% CI 1.10 - 2.83; p= 0.03; HR = 4.86, 95% CI 1.38 - 1.11; p= 0.01) respectively. Similarly, upregulated of ALDH1A1, CXCL9 and FGL2 were associated with a better prognosis (HR = 0.17, 95% CI 0.05 - 0.50; p= 0.003; HR = 0.15, 95% CI 0.04 - 0.50; p = 0.004; HR = 0.21, 95% CI 0.07 - 0.60; p = 0.009), respectively.

We identified potentially beneficial gene expression signatures (OS and pCR) for neoadjuvant chemotherapy, suggesting that these markers validated in a prospective study can be used in selecting patients for neoadjuvant chemotherapy in TNBC.

Citation Format: Ana J. Freitas, Caroline R. Nunes, Rhafaela L. Causin, Iara V. Santana, Marco A. Oliveira, Stéphanie Calfa, Cristiano P. Souza, Márcia M. Marques. Gene signature predicts pathological complete response in triple negative breast cancer patients: NACATRINE trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2175.