Impact of HER2 Status Assessed by Immunohistochemistry on Treatment Response in Patients with Metastatic Breast Cancer Receiving Trastuzumab Emtansine

<i>Background and Objectives</i>: HER2-positive breast cancer accounts for approximately 20–30% of all breast cancer cases and is associated with aggressive tumor behavior. Trastuzumab emtansine (T-DM1), an antibody-drug conjugate targeting HER2, is a standard second-line therapy for pat...

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Main Authors: Sila Oksuz, Oguzcan Kinikoglu, Ugur Ozkerim, Yunus Emre Altintas, Deniz Isik, Heves Surmeli, Hatice Odabas, Seval Ay, Tugba Basoglu, Nedim Turan
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Medicina
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Online Access:https://www.mdpi.com/1648-9144/61/5/819
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Summary:<i>Background and Objectives</i>: HER2-positive breast cancer accounts for approximately 20–30% of all breast cancer cases and is associated with aggressive tumor behavior. Trastuzumab emtansine (T-DM1), an antibody-drug conjugate targeting HER2, is a standard second-line therapy for patients with metastatic disease. However, the impact of HER2 immunohistochemistry (IHC) expression levels on T-DM1 efficacy remains unclear. <i>Materials and Methods</i>: This retrospective study examined 87 patients with HER2-positive metastatic breast cancer who received T-DM1 following trastuzumab-based therapy. Patients were divided into IHC 2+ and IHC 3+ groups. Progression-free survival (PFS) and overall survival (OS) were evaluated via Kaplan–Meier analysis, and group comparisons were conducted using the log-rank test. <i>Results</i>: The median progression-free survival (PFS) for the entire cohort was 7.3 months (95% CI: 5.277–9.323), with a numerically longer PFS in the IHC 3+ group (8.4 months, 95% CI: 5.915–10.952) compared to the IHC 2+ group (6.3 months, 95% CI: 4.178–8.422). However, this difference was insignificant (HR: 0.91, 95% CI: 0.61–1.35; <i>p</i> = 0.778). Similarly, the median overall survival (OS) was 23.3 months (95% CI: 18.039–28.495), with the IHC 3+ group exhibiting a slightly longer OS (24.5 months, 95% CI: 18.600–30.400) compared to the IHC 2+ group (23.2 months, 95% CI: 12.387–34.147). Again, this difference did not reach statistical significance (HR: 0.93, 95% CI: 0.63–1.42; <i>p</i> = 0.369). <i>Conclusions</i>: Although the association between HER2 IHC 3+ expression and longer PFS and OS is promising, the lack of statistical significance suggests that IHC-based HER2 stratification alone may not be sufficient to predict the response to T-DM1. The potential of conducting prospective studies with larger cohorts and comprehensive molecular profiling to refine predictive biomarkers for optimizing therapeutic outcomes in HER2-positive metastatic breast cancer is a beacon of hope and should be pursued with optimism.
ISSN:1010-660X
1648-9144