A retrospective analysis within the MINDACT trial

In this poster, Prof Christine Desmedt, Head of the Laboratory for Translational Breast Cancer Research at the University Hospitals Leuven in Belgium, aimed to investigate which biological characteristics are associated with recurrence using the transcriptomic data from the MINDACT trial.

These are the results from a collaborative retrospective analysis within the MINDACT trial, focusing on patients with invasive carcinoma of no special type (NST), the most common pathological subtype. The primary objective was to delve beyond existing commercial tests, such as MammaPrint, and unravel additional processes associated with breast cancer recurrence. Attention was specifically directed at two groups with discordant clinical and genomic scores assigned by MammaPrint. The first group exhibited a clinical low but genomic high-risk score, while the second group had a clinical high but genomic low-risk score, totalling over 1,200 patients. Disparities in clinical characteristics were noted, with the clinical low score group having fewer cases of nodal involvement.

Analysing disease-free survival and distance relapse-free survival, the study identified a pivotal role of proliferation, as indicated by Ki-67 levels, in both groups. Higher Ki-67 was associated with a worse prognosis. Delving into gene expression data revealed biological processes beyond MammaPrint’s scope. Cell cycle-related processes were consistently associated with a worse prognosis in both groups, even when adjusting for Ki-67. Notably, certain processes linked to immune responses, HER2 expression, and PI3K signalling emerged as associated with a better prognosis.

This analysis represents a crucial advancement in discerning processes linked to recurrence that extend beyond current testing capabilities and clinical variables. The next phase involves validation in other extensive trials or retrospective series to refine patient prognostication and potentially enhance our understanding of breast cancer recurrence mechanisms.

Reference:

Desmedt C. et al., Different molecular processes are associated with recurrence in the clinical high- genomic low risk (cH/gL) and clinical low- genomic high risk (cL/gH) groups of the MINDACT clinical trial – SABCS 2023, #P01-14-11