Prognostic and Predictive Value of Expression in Early Breast Cancer and by Molecular Subtype.

BACKGROUND

LIV1 is a transmembrane protein that may become a new therapeutic target through the development of antibody-drug conjugates (ADCs). Few studies are available regarding the assessment of expression in clinical breast cancer (BC) samples.

METHODS

We analyzed mRNA expression in 8982 primary BC. We searched for correlations between expression and clinicopathological data, including disease-free survival (DFS), overall survival (OS), pathological complete response to chemotherapy (pCR), and potential vulnerability and actionability to anti-cancer drugs used or under development in BC. Analyses were performed in the whole population and each molecular subtype separately.

RESULTS

LIV1 expression was associated with good-prognosis features and with longer DFS and OS in multivariate analysis. However, patients with high expression displayed a lower pCR rate than patients with low expression after anthracycline-based neoadjuvant chemotherapy, including in multivariate analysis adjusted on grade and molecular subtypes. -high tumors were associated with higher probabilities of sensitivity to hormone therapy and CDK4/6 inhibitors and lower probabilities of sensitivity to immune-checkpoint inhibitors and PARP inhibitors. These observations were different according to the molecular subtypes when analyzed separately.

CONCLUSIONS

These results may provide novel insights into the clinical development and use of LIV1-targeted ADCs by identifying prognostic and predictive value of expression in each molecular subtype and associated vulnerability to other systemic therapies.