Biomarker (Genomic) Testing in Metastatic Lobular Breast Cancer

Biomarker (genomic) testing in tissue or liquid biopsy may be useful in identifying genomic mutations that have approved drugs or are being studied in clinical trials for patients with metastatic invasive lobular carcinoma (ILC), also known as metastatic lobular breast cancer.

Because of the growing understanding about different biomarkers and what they may mean for future treatment for patients with metastatic ILC, it is increasingly common that biopsy of new metastatic sites or, upon progression, genomic testing conducted either by tissue or liquid biopsy be considered. These tests are done with the hope that they will identify mutations for which there are current targeted treatments or for which it is expected that there will be targeted treatments in the future.

Ethan Sokol, lead author from Foundation Medicine, presented a poster during a SABCS 2020 Spotlight Session on genomic mutations in the largest dataset of metastatic ILC to date looking at differences in clinically actionable biomarkers and therapy resistance mutations across ILC; biopsied from different metastatic sites, as well as Tumor Mutationsl Burden (the number of mutations in a tumor).

This poster, (PD801), titled Comprehensive Genomic Profiling (CGP) of metastatic invasive lobular carcinomas reveals heterogeneity in immune biomarkers and resistance alterations across biopsy sites, examines the landscape of 1900 metastatic ILC profiled for genomic mutations in >300 genes using the Foundation Medicine test. The authors wanted to understand if there were differences in clinically actionable biomarkers and therapy resistance mutations across ILC; biopsied from different metastatic sites. The group examined biomarkers associated with response to immune checkpoint inhibitors (ICPI), a class of drugs that activates the immune system to fight the tumor. High TMB and PD-L1 staining have been associated with response to these agents. The authors found elevated rates of high TMB in ILC when compared to IDC, with the highest rates in GI and skin metastases. While PD-L1 staining was lower in ILC metastases overall, high rates were observed in GI and skin metastases. These findings suggest that ILC GI and skin metastases may be potential candidates for Immune Checkpoint Inhibitors (immunotherapy) therapy.

PIK3CA alterations were observed in a large number of ILC metastases (58%). This may predict sensitivity to PI3K pathway inhibitors. Prevalence was similar across sites, meaning that women with ILC may benefit from PI3K-targeting agents regardless of where their tumor has metastasized. The authors also found a high prevalence of mutations associated with resistance to ER-targeted agents (e.g. mutations in ESR1, NF1, and ERBB2). Significant differences were observed in the types of resistance mutations across sites (for example, ERBB2 mutations were common in liver metastases (21%) but were rare in GI and female reproductive metastases (3%).

This work has potential implications for post-progression treatment options and overall, these findings confirm that ILC is a unique genomic disease relative to IDC. The study further identifies unique vulnerabilities of ILC based on the site of metastasis.

Lay Summary by Ethan Sokol, Foundation Medicine

To read the full published abstract, click here.

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