The luminal breast cancer subtype has enhanced expression of the ERBB3 oncogene, and depleting the ERBB3 protein with an antibody promotes cancer cell death and decreases tumor growth in vitro, according to a new study.
Breast cancer can be divided into four major subtypes based on molecular and genetic information from tumors. Each subtype has a different prognosis. Subtype should be considered when making treatment decisions.
Many human cancers have aberrant regulation of the erythroblastosis oncogene B (ERBB) family of receptor tyrosine kinases and their ligands. Luminal breast cancer cells require ERBB3 for both growth and survival. This study tested the hypothesis that ERBB3 drives the growth of the luminal subtype of breast cancer.
In this study, led by Rebecca Cook, PhD, of Vanderbilt University in Nashville, Tennessee, ERBB3 was upregulated in luminal tumor samples and in cancer cell cultures that were treated with the cancer drug fulvestrant. Fulvestrant is an inhibitor of the estrogen receptor. The authors also found that fulvestrant treatment in combination with an anti-ERBB3 antibody decreased both tumor cell survival and growth. The data, published in the Journal of Clinical Investigation (2013; doi:10.1172/JCI66764), suggest that ERBB3 could be a target for treating fulvestrant-resistant breast cancers.
The research found that the upregulation of ERBB3 is inherent to many luminal breast cancer cells, rather than that upregulation being imposed, selected for, or acquired over time. Luminal A/B breast cancers have the highest levels of ERBB3 mRNA among breast cancer subtypes, and the researchers suggest that this may be because ERBB3 is required for cell survival in the untransformed luminal mammary epithelium, but not the untransformed basal epithelium. Luminal breast cancer may occur because of the transformation of a luminal mammary epithelial cell, and the pathways regulating the development of these cells may be commandeered by luminal breast tumors. This study found that, not only is the growth and survival of luminal breast cancer driven by ERBB3, but ERBB3 is a potential therapeutic target, as adding an anti-ERBB3 antibody improved the response of luminal breast cancer to antihormonal therapy.