Nw-Hydroxy L-Arginine (NOHA): A Promising Biomarker of Response to Neoadjuvant Therapy in the Management of Triple Negative Breast Cancer.

BACKGROUND

Oncologists lack effective point-of-care biomarkers to rapidly adapt curative-intent triple negative breast cancer (TNBC) neoadjuvant therapy (NT). Previous work reveals that Nw-hydroxy-L-Arginine (NOHA) is an easily measured and sensitive plasma-based biomarker for breast cancer hormone receptor status, disease stage, and grade, with reduced levels correlating with the presence of estrogen receptor negative and high-risk disease.

AIMS: This pilot study examined NOHA's potential as a marker of both TNBC disease presence and treatment exposure to curative intent TNBC NT, including evaluation of the relationship between longitudinal NOHA normalization and measures of pathologic response.

METHODS AND

RESULTS

NOHA concentration was assessed pre-NT and then longitudinally at five timepoints, including pre- and post-operatively, among 31 TNBC patients undergoing definitive surgery following receipt of NT. NOHA concentrations were low pre-NT and increased progressively toward healthy control levels during and after neoadjuvant therapy and post-operatively in all patients, yet showed no difference comparing those achieving pathologic complete response versus pathologic partial response or stable disease. Levels did not vary based on receipt of pembrolizumab, clinical characteristics, or presence of non-cancer comorbidities.

CONCLUSION

These findings support NOHA's potential as a marker of disease presence and treatment exposure rather than differential response. Larger validation studies are needed to determine whether serial levels can be used to optimize treatment decision-making or improve outcomes in high-risk populations.