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Prognostic Value of Trop-2 Expression in Nonmetastatic Triple-Negative Breast Cancer and Correlation With Emerging
William Jacot1,2,3,4, Marie-Christine Chateau2, Simon Thezenas5,6
1Department of Medical Oncology, Montpellier Cancer Institute Val d'Aurelle, Montpellier, France.
Introduction:
Triple-Negative Breast Cancer (TNBC) is an aggressive breast cancer subtype, in which targeting the Trophoblast cell-surface antigen-2 (Trop-2), using antibody-drug conjugates (ADC), results in significant clinical improvement. However, clinicopathological correlations with Trop-2 protein expression levels remain limited in TNBC patients.
Methods:
Here we assessed by immunohistochemistry (IHC) using the mouse monoclonal anti-Trop-2 antibody (Enzo, Cat. ENZ-ABS380) cell membrane Trop-2 expression levels and classified them in 3 H-Score classes, low (< 100), moderate (100-200), and strong (> 200). We also evaluated potential associations with clinicopathological variables including basal-like and molecular apocrine phenotypes, immune infiltrate characteristics, PTEN and PIK3CA alterations in a large retrospective series of 228 nonmetastatic TNBC patients.
Results:
Trop-2 expression was evaluated as low, moderate and strong in 12.3%, 28.9%, and 58.8% of the cases respectively. Only 3 tumors showed no Trop-2 expression. Interestingly, Trop-2 expression was not associated with classical breast cancer clinicopathological variables, HER2 levels or molecular subtype, neither did we observe an association with relapse-free survival. Only a marginal association with pT1 tumors was observed, which tended to express increased levels of Trop-2 protein. In order to determine possible fluctuations of Trop-2 protein expression levels during the course of the disease, we studied a second independent cohort of 18 TNBC comprised of serial tissue samples (diagnostic biopsies, surgical resection specimens and corresponding patients-derived xenografts (PDX)). Trop-2 levels remained globally stable between cognate tumor samples with only one exception corresponding to a Trop-2-negative tumor giving rise to a Trop-2-positive PDX.
Conclusions:
As Trop-2 expression appears nearly constant and independent of classical TNBC variables and outcome, association of anti-Trop-2 therapies with other targeted therapies can be evaluated without reducing the population in specific TNBC subgroups.
