9IN - Biomarkers of Residual Disease: the Classics and the New Discoveries

Abstract

ABSTRACT The persistence of a residual tumour (RT) after neoadjuvant therapy (NAT) for breast cancer (BC) is associated to poorer patient prognosis. Adjuvant treatment is aimed to prevent BC recurrences and fatal metastases, however, biomarkers able to guide physicians in choosing best therapy after NAT and surgery for BC are still scarce. Recent works have pointed out the significant biological differences between the initial (pre-NAT) and residual (post-NAT) BC. Instead of making the decision about the adjuvant treatment on the basis of the tumour characteristics at diagnosis, there is a growing tendency of using the RT pathobiological features as prognostic biomarkers. Indeed, numerous studies have reported changes of the “classical” biomarker (ER, PR, HER2) status after NAT for BC. The most frequently observed change is loss or reduction of biomarker expression, associated practically always with a resistant disease. Moreover, high throughput technologies of gene/protein expression analysis have shed light on specific molecular modifications arising in the post-NAT BC RT, which offers opportunities for targeting. In triple-negative BC (TNBC), gene expression analysis demonstrated enrichment of RT in pathways driven by phosphoinositide 3-kinase, small G proteins and energy metabolism, while the immune cell-derived and the sonic hedgehog pathways were depleted. In addition, a recent comprehensive analysis identified low concentrations of dual specificity protein phosphatase 4 (DUSP4), an ERK phosphatase, as one of the mechanisms of resistance to NAT of basal-like TNBC. In ER-positive BC, loss of ER expression, increase in Ki67 and reduction in IGF-1R in the post-NAT RT were observed. Similarly, molecular profiling of ER+ BC before and after treatment by aromatase inhibitors has confirmed strong down-regulation of proliferation-related and ER-related genes in the post-treatment RT, while collagen- and chemokine-related genes were upregulated, indicating a role of immune pathways in resistance. This presentation will provide a comprehensive overview of particular molecular features of BC after NAT which can potentially serve as indicators of ways to combat the resistance and prevent local and distant recurrences. Disclosure: All authors have declared no conflicts of interest.