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Abstract
Introduction. Triple-negative breast cancer (TNBC) is a heterogeneous disease. Initially clinicians believed that anti-HER2-targeted therapy could not be used in cases of triple-negative (ER-, PR-, and HER2-negative) cancers. Later, new anti-HER2 antibody-drug conjugates (ADCs) were developed. The structure of ADCs comprises an antibody, a linker, and a cytotoxic payload. Therefore, experts are increasingly arguing for the revision of the criteria used to assess HER2-negative tumors and determine the HER2-low status among known molecular subtypes of breast cancers, including TNBC.
Aim. To summarize scientific data on the significance of HER2-low status in the choice of HER2-targeted therapy for patients with triple-negative (ER-, PR-, and HER2-negative) cancers.
Materials and methods. The study is based on PubMed/Medline and Google databases search results.
Results. HER2-low BCs comprise about 50% of all breast cancers and 35% of triple-negative (ER-, PR-, and HER2-negative) cancers correspondently. Studies on anti-HER2 ADCs therapy in treating HER2-low tumors show promising results. This justifies the need to revise treatment selection algorithm for TNBC. For example, preliminary data suggest that in metastatic HER2-low and HR-negative BCs median progression-free survival (PFS) time can be 5.6 months longer compared to life expectancy of survivors treated with chemotherapy (8.5 vs 2.9; RR 0.46, [95 % CI: 0.24, 0.89]). Median overall survival time can exceed survival time after chemotherapy up to 9.9 months (18.2 vs 8.3; RR 0.48, [95% CI: 0.24, 0.95]).
Conclusion. Understanding the heterogeneity of HER2 status and further clinical development of guidelines for prescribing anti-Her2 ADCs could lead to a significant change in routine therapy for at least 1/3 of all patients with triple-negative (ER-, PR-, and HER2-negative) cancers, who have exhausted other treatment options.
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