The TNBC-DX Test for Predicting pCR and Survival Outcomes Among Patients with Early-Stage Triple-Negative Breast Cancer

A novel test for predicting short- and long-term outcomes among patients with triple-negative breast cancer (TNBC), the TNBC-DX was found to predict the pathological complete response (pCR) to neoadjuvant taxane-carboplatin among patients with stage I to III TNBC. It may also help predict a patient’s long-term survival when not treated with neoadjuvant anthracycline/cyclophosphamide, independent of pembrolizumab use.

As Miguel Martín, MD, Hospital General Universitario Gregorio Marañón, Madrid, Spain, and coauthors wrote, “Identification of biomarkers to optimize treatment strategies for early-stage triple-negative breast cancer is crucial.” Using the recently developed 27-gene HER2DX genomic test for early-stage HER2-positive breast cancer as a reference, the TNBC-DX was developed. Information from 1,259 patients with early-stage TNBC were also used to improve the model. Information from these patients was not used in the formal validation of this test. TNBC-DX incorporates 10-gene core immune gene module, 4-gene tumor cell proliferation signature, tumor size, and nodal staging. Integrating these factors using machine-learning, 2 scores are produced (0 to 100) to predict pCR and long-term survival outcomes.

Independent validation of TNBC-DX included 527 patients with stage I to III TNBC undergoing neoadjuvant chemotherapy from 3 studies: WSG-ADAPT-TN where patients received nab-paclitaxel plus gemcitabine or carboplatin, MMJ-CAR-2014-01 where they received carboplatin plus paclitaxel, and NeoPACT where they received carboplatin plus docetaxel and pembrolizumab. The objective of this validation study was to evaluate the association between TNBC-DX and efficacy outcomes such as pCR, distant disease-free survival (DDFS) or event-free survival (EFS), and overall survival. 

Among the 2 cohorts including patients not treated with pembrolizumab, TNBC-DX score was significantly associated with pCR, with adjustment for clinicopathological variables and treatment regimen (odds ratio [OR] per 10-units increment, 1.34; P < .001) . The pCR rates for TNBC-DX pCR-high, -medium, and -low, were 56.3%, 53.6%, and 22.5%, respectively (OR for pCR high-risk vs low-risk, 3.48; P < .001). The TNBC-DX score was also significantly associated with DDFS and OS. Among patients who were treated with pembrolizumab, TNBC-DX scores were significantly associated with pCR, EFS, and OS.

As Dr Martín, et al, concluded, “the TNBC-DX genomic test offers a valuable tool for predicting pCR and survival outcomes in early-stage TNBC.” They added that this development “supports the shift toward more personalized and potentially less intensive treatment options, helping to better align therapeutic strategies with the unique profiles and needs of patients with TNBC.”

Source:

Martín M, Stecklein SR, Gluz O, et al. TNBC-DX genomic test in early-stage triple-negative breast cancer treated with neoadjuvant taxane-based therapy. Ann Oncol. Published on October 15, 2024. doi: 10.1016/j.annonc.2024.10.012