Clinical and Prognostic Differences Between HER2 IHC 2+ and HER2 IHC 3+ Populations in HER2+ MBC

To better understand the relationship between HER2 immunohistochemistry (IHC) staining and treatment outcomes, the current study compared the clinical variables, metastatic patterns, and prognoses in the IHC 2+ and IHC 3+ patient cohorts in HER2+ metastatic breast cancer (MBC).

The analysis population included patients from the GIM14 study database with HER2+ MBC, as determined by an HER2 IHC staining score of 3+ or 2+. Univariate and multivariate Cox regression models were used to identify prognostic factors for overall survival (OS) and time to treatment failure (TTF).

A total of 762 HER2+ MBC patients were included in the analysis. Of these, 39% had an IHC score of 2+ and 61% had an IHC score of 3+.

In univariable analysis, HER2 IHC 3+ was more likely to be associated with SK metastases (odds ratio [OR], 1.76; P =.043) and less likely to be associated with LI (OR, 0.71; P =.031), LU (OR, 0.70; P =.036), and LN (OR, 0.63; P=.002) metastases compared with IHC 2+; LN metastases maintained statistical significance (OR, 0.62; P=.004) in multivariate analysis.

In the IHC 3+ subgroup, negative prognostic factors identified were neoadjuvant trastuzumab (hazard ratio [HR], 1.55; P=.032), adjuvant radiotherapy (HR, 1.34; P=.042), neoadjuvant chemotherapy (HR, 1.63; P=.002), CNS metastases (HR, 1.98; P =.002), and LI metastases (HR, 1.68; P<.0001); CNS metastases (HR, 1.73; P=.028) and LI metastases (HR, 1.47; P=.017) continued to be prognostic in multivariate analysis. In the IHC 2+ subgroup, LI metastases (HR, 1.67; P=.005) was the only prognostic factor associated with worse OS.

In the overall HER2+ population, multivariate analysis identified neoadjuvant chemotherapy (HR, 1.49; P=.009), CNS metastases (HR, 1.53; P=.003), and PL metastases (HR, 1.50; P=.036) as negative prognostic factors for OS, whereas PL metastases (HR, 1.74; P=.048) was associated with a shorter TTF.

Based on these exploratory data, it was concluded that an IHC score of 3+ is less likely to be associated with LN and visceral metastases HER2+ MBC, and that site of metastasis has prognostic significance.


Dri A, Blondeaux E, Bighin C, et al. HER2 immunohistochemistry (IHC) expression in HER2-positive (HER2-pos) metastatic breast cancer (mBC): clinical and prognostic differences between IHC 2+ and IHC 3+ populations. Presented at the 46th San Antonio Breast Cancer Symposium Annual Meeting, December 5-9, 2023; San Antonio, TX: Abstract PO4-04-05.

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