Axillary lymph node (ALN) metastases play a central role in the management of BC as they have been shown to be the most important factor predicting distant relapse. One may envision that rare sub-clones in the primary tumour, capable of metastasizing, are disseminated to the axilla where they expand. However, little is known of the genetic alterations that characterize ALNs.
In the present project, we hypothesize that ALN metastases are a surrogate of intra-tumor heterogeneity at the primary site and could represent a more representative picture of the alterations characterizing heterogeneous primary BC.
By using state of the art next generation sequencing technologies we aim to gather a broader knowledge of the genetic alterations of ALN metastases and matched primary tumours, in order to assess the added value of characterizing ALN in the context of inta-trumor heterogeneity and molecularly targeted therapies.
Results from the project has suffered delays, much due to temporary facility close-downs because of the Covid-19 situation. However, we have completed sample collection and performed high quality DNA extraction from breast cancer belonging to two main subgroups; tumours associated with a high number of lymph metastatic deposits, from which both the primary tumour and corresponding lymph nodes have been processed, and a control group of node negative tumours. In total, samples from 93 patients have been included in the project (49 ALN positive and 44 ALN negative). Multiple regions from the primary tumours have been samples as well as a total of 98 ALNs from the 49 ALN positive patients, mounting to a total of 372 samples. These samples have successfully undergone whole exome sequencing (WES) and as such, all wet-lab analyses are completed.
The generated data is currently undergoing extensive bioinformatics analyses. We envison the results to be of significant importance to our understanding of the prognostic role of lymph node metastases (node numbers) to breast cancer prognosis. If it turns out that this may be related to intra-tumour clonal diversity, as hypothesised, we envision it may pave the way for e better rational understanding the metastatic process in breast cancer in general and, as such, improve therapy and outcome further.