Abstract
In the case of breast cancer, receptors of the large HER family play an important role that undergoes gradual evolution in association with the biological development, both in the diagnostic and therapeutic fields. Originally, HER-2 positivity in breast cancer was an unfavourable prognostic factor in itself.
This has changed due to modern treatment with monoclonal antibodies. The final analysis of data from the CLEOPATRA trial has been another landmark.
This trial focused on the benefit of adding the monoclonal antibody pertuzumab to standard treatment with trastuzumab and docetaxel. Pertuzumab binds to the same target as trastuzumab, yet at a different binding site, thus inhibiting heterodimerization of the HER-2 and HER-3 receptors.
In fact, dimerization of HER-2 and of other members of the HER family is the major driving mechanism of tumour cell growth and survival. Pertuzumab itself has minimal anticancer efficacy; therefore, it is used exclusively in combination with trastuzumab.
Hence, this combined approach improves HER-2 signalling pathway inhibition by disrupting the dimerization of HER-3 and HER-2 receptors. What appears to be intriguing, however, is the use of HER-3 expression as a possible prognostic marker in TNBC predominantly in association with pregnancy and breast-feeding.
The HER-3 receptor is supposed to be involved not only in cell survival and proliferation, but also in the regulation of PD-L1 expression. It could thus be a potential target for immunotherapy.
Indeed, the view of the HER-3 receptor is likely to be much more complex and, as it seems, overexpression of this receptor will have both negative and positive prognostic significance.