Aileen I. Fernandez, PhD, postdoctoral fellow, Yale School of Medicine, discusses the utility of fam-trastuzumab deruxtecan-nxki (Enhertu) in HER2-low breast cancer.

Trastuzumab deruxtecan targets HER2 and has demonstrated efficacy in patients who have low levels of HER2 expression, Fernandez says. Trastuzumab (Herceptin) has utility in patients with high levels of HER2 expression, Fernandez explains. However, if patients have immunohistochemistry 0 or 1+ disease, they won’t respond to trastuzumab. 

Trastuzumab deruxtecan is an antibody-drug conjugate comprised of an anti-HER2 antibody, a cleavable linker, and a topoisomerase inhibitor, Fernandez continues. If trastuzumab deruxtecan identifies any level of HER2 expression, it is then able to latch onto the cell and deliver its cytotoxic payload, Fernandez says. Then, it goes back into the bloodstream targeting the neighboring cells that do not have HER2 expression, which is why it has activity in HER2-low disease, Fernandez concludes

Videos

Aileen I. Fernandez, PhD, discusses the utility of fam-trastuzumab deruxtecan-nxki in HER2-low breast cancer. 


Dr. Fernandez on the Utility of Trastuzumab Deruxtecan in HER2-Low Breast Cancer 

Aileen I. Fernandez, PhD, postdoctoral fellow, Yale School of Medicine, discusses the need to refine immunohistochemistry (IHC) testing in HER2-positive breast cancer.

Findings from a study evaluating low HER2 expression in patients with breast cancer underscored a discrepancy between the frequency clinicians agreed upon immunohistochemistry (IHC) results of 0 vs 1+ or 2+ vs 3+. Clinicians were more likely to agree upon diagnoses of IHC 2+ or 3+ compared with 0 or 1+.

These findings indicate that IHC testing results should be analyzed carefully, Fernandez explains. Historically, IHC 2+ or 3+ results were focused on because they informed treatment selection with trastuzumab (Herceptin). However, as scoring accuracy is imperfect, misassignment remains a risk, Fernandez explain.

Developing a new test, answering preanalytical questions, and standardizing testing across the board would be helpful, Fernandez says. Moreover, in reading IHC test results, differences with the machines and the clinicians interpreting the results may provide insight as to why there remains disagreement in IHC analysis.




Moreover, as the field of breast cancer continues to evolve, other therapies targeted toward biomarkers beyond HER2 will emerge, further underscoring the need for improved testing, concludes Fernandez.

Aileen I. Fernandez, PhD, discusses the need to refine immunohistochemistry testing in HER2-positive breast cancer.  



Dr. Fernandez on the Need to Refine Immunohistochemistry Testing in HER2+ Breast Cancer 

Aileen I. Fernandez, PhD, postdoctoral fellow, Yale School of Medicine, discusses the results of a study examining low HER2 expression in breast cancer.

During a poster session at the 2021 San Antonio Breast Cancer Symposium, findings from a study evaluating low HER2 expression in patients with breast cancer were presented. In both cohorts analyzed, the analysis revealed a discrepancy between the frequency clinicians agreed upon immunohistochemistry (IHC) results of 0 vs 1+ or 2+ vs 3+. Moreover, clinicians were more likely to agree upon diagnoses of IHC 2+ or 3+ compared with 0 or 1+, Fernandez explains. 

These findings confirm the hypothesis of the study, Fernandez says. Moreover, the results have clinical implications because if a patient presents with IHC 2+ disease, for example, they receive fluorescence in situ hybridization testing and will qualify to receive trastuzumab (Herceptin). Conversely, patients with IHC 1+ disease who are diagnosed with IHC 0 breast cancer won’t qualify for trastuzumab, which is not optimal, Fernandez concludes.

Aileen I. Fernandez, PhD, discusses the results of a study examining low HER2 expression in breast cancer.

Aileen I. Fernandez, PhD

Articles

Dr. Fernandez on the Utility of Trastuzumab Deruxtecan in HER2-Low Breast Cancer

Dr. Fernandez on the Need to Refine Immunohistochemistry Testing in HER2+ Breast Cancer

Dr. Fernandez on the Results of a Study Examining Low HER2 Expression in Breast Cancer