Can Biopsies of Liver Metastases Improve Treatment Choice?

Analyses of the levels of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) are standard practice following an initial breast cancer diagnosis. This characterization is important to subtype the cancer and determines the choice of therapy. 

Cross section of a human liver, taken at autopsy examination, showing multiple large pale tumor deposits. The tumor is an adenocarcinoma derived from a primary lesion in the body of the pancreas.

It is currently not routine practice to re-biopsy metastatic tissue to re-evaluate treatment options based on tumor characteristics. This is despite the fact that, upon progression to metastasis, cancers can evolve, resulting in changes in mutations and expression levels of specific markers. Biological changes between the primary and secondary tumors can occur, but have not been systematically studied.

Researchers at the University of Milan sought to assess the clinical relevance of biopsying primary breast cancers and secondary metastatic liver lesions to evaluate the occurrence of important markers. They asked whether changes occur frequently enough to warrant the biopsy of secondary cancers, which could potentially improve treatment options. The results of the 1250-patient retrospective study are published ahead of print in the Annals of Oncology (doi:10.1093/annonc/mdq751). 

The study found discordance rates for ER, PgR, and HER2 between primary tumor and liver metastases of 14.5%, 48.6%, and 13.9% (24 of 172 patients), respectively. 5.9% of patients changed from a negative to a positive HER2 status. A discordance of status of any of the three biomarkers led to change in treatments for 12.1% (31 of 255) of patients. 

Interestingly, the study observed a concomitant decrease in ER and PgR expression along with liver metastases turning HER2-positive. The authors hypothesize that there is potential cross-talk between pathways that suggests that endocrine resistance is being mediated by HER2 up-regulation within the tumor.  

Although this was a retrospective, non-blinded study, it was strengthened by being a single-institution study. Thus, all pathology, biopsies, and assays carried out in the same laboratory thereby minimizing inter-laboratory variability. 

Improving and optimizing the care of patients with metastatic breast cancer relies on a thorough understanding of the biology of the disease and how it may differ between the primary and the metastatic disease setting. The major reasons that biopsies of metastatic breast cancer are not part of standard care are the lack of previous evidence of utility, reluctance of allowing an invasive, surgical procedure for an advanced-disease patient, and potential harm of a false-negative result. When safe and relatively easy to carry out, a biopsy of metastatic disease has the potential to impact treatment of choice. However, more studies are necessary before metastatic breast cancer biopsies become standard of care.