Human Epidermal Growth Factor Receptor-2 a Strong Indicator of Breast Cancer Prognosis

Human epidermal growth factor receptor-2 (HER-2) expression may be a key indicator of recurrence risk in patients with breast cancer, though PIK3CA mutations have no prognostic value, according to a recent study. 

Overexpression of HER-2 occurs in about 15-20% of invasive breast cancer patients and is associated with a more aggressive tumor phenotype that can lead to worse clinical outcomes if left untreated. Tests for HER-2 are widely performed in clinical settings to determine whether targeted therapies such as trastuzumab or pertuzumab should be administered. Similarly PIK3CA is a well-known accomplice of HER-2, activating key pathways that support tumor growth and protect HER-2 from targeted therapies.
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To determine the prognostic value of HER-2 and PIK3CA, researchers led by Mandy Kiderlen, MD, Leiden University Medical Center (Leiden, The Netherlands), examined the expression of both in a set of patients 65 years and older diagnosed with breast cancer between 1997 and 2004 in The Netherlands. 

Researchers were able to identify 1698 patients for analysis, 269 of whom had a HER-2 expression score of 2+ and 103 of whom had a score of 3+. Among all patients where PIK3CA status was available, 30% presented with the mutation, although it was not associated with HER-2 overexpression. The Primary endpoint for analysis in the study was relapse-free period and the secondary endpoint was relative survival. Results were published in Breast Cancer Research and Treatment.

Median follow-up for relapse-free period was 5.3 years and results showed that HER-2 negative patients had a cumulative recurrence risk of 12%, which was equal to patients with a HER-2 expression of 2+ but significantly less than the 34% found in patients with HER-2 scores of 3+. There was no statistically significant difference in relapse-free survival between patients who did or did not have a PIK3CA mutation. 

For relative survival, the median follow-up was 8.9 years and patients with a HER-2 score of 2+ again showed equal outcomes compared to patients who did not express HER-2. However, patients with a score of 3+ had significantly worse relative survival. The relative survival of patients without PIK3CA mutations was 82% at 10 years compared to 81% in patients who did have the mutation, indicating no significant difference. 

Researchers did note that there were some limitations in their study, most significantly the lack of tumor material available for all patients in the cohort, though steps were taken to try and mitigate this problem.

“Our present study demonstrates that HER-2 overexpression is a strong and independent predictor of worse prognosis, tested in a representative population of older breast cancer patients and even after taking into account competing risk of mortality due to other reasons,” concluded researchers. 

Future research should focus on anti-HER-2 regimens that minimize toxicity for the elderly population.—Sean McGuire 


Engels CC, Kiderlen M, Bastiaannet E, et al. The clinical value of HER-2 overexpression and PIK3CA mutations in the older breast cancer population: a FOCUS study analysis. [Published online March 11, 2016]. Breast Cancer Res Treat. doi: 10.1007/s10549-016-3734-y.