The article discusses the importance of accurately distinguishing HER2-low from HER2-negative breast cancer, as novel ADCs have demonstrated activity in a large population of patients with HER2-low-expressing BC. While current guidelines recommend a dichotomous classification of HER2 as either positive or negative, the emergence of the HER2-low concept calls for standardization of HER2 testing in breast cancer, using currently available assays to better discriminate HER2 levels. This review covers the evolution and latest updates of the ASCO/CAP guidelines relevant to this important biomarker in breast cancer, including still-evolving concepts such as HER2 low, HER2 heterogeneity, and HER2 evolution. Our group presents the latest Mexican recommendations for HER2 status evaluation in breast cancer, considering the ASCO/CAP guidelines and introducing the HER2-low concept. In the era of personalized medicine, accurate HER2 status assessment remains one of the most important biomarkers in breast cancer, and the commitment of Mexican pathologists to theragnostic biomarker quality is crucial for providing the most efficient care in oncology.

PD-L1 is an important predictive biomarker for treatment by immune checkpoint inhibitors (ICIs). ICIs are now indicated for the treatment of various cancer depending on the level of expression of PD-L1 on tumor cells. PD-L1 testing is done using immunohistochemistry with five different assays approved as companion diagnostic for ICIs. However, these assays have different score reporting methods and do not accurately measure PD-L1 expression. Exosomal PD-L1 testing has recently emerged as an alternative for cell-surface PD-L1 testing however studies are still premature and more extensive knowledge about this new potential biomarker is needed.
Lay abstract Immunotherapy is a new strategy for cancer treatment that aims to reactivate the body’s own immune system, originally disabled by the tumor, to fight the malignancy. Immune checkpoint inhibitors are compounds developed for this purpose. However, their efficacy is subject to the abundance of their target, PD-L1, on the surface of cancer cells. Conventional PD-L1 testing through tumor biopsy has multiple technical drawbacks. Another form of PD-L1 secreted by the tumor into the circulation has emerged as a potential target for assessing immune checkpoint inhibitors efficacy but studies are still in their preliminary stages and further testing is required.