Prediction of Trastuzumab Benefit in HER2-Positive Breast Cancers : Is It in the Intrinsic Subtype?
Menée à partir de l'analyse d'échantillons tumoraux prélevés sur 1 392 patientes atteintes d'un cancer du sein HER2+ et ayant reçu une chimiothérapie adjuvante en combinaison ou non avec le trastuzumab, cette étude évalue l'association entre le sous-type intrinsèque de la tumeur et la réponse au trastuzumab
The HER2 (ERBB2) gene is amplified and overexpressed in approximately 15% of breast cancers, and its protein product human epidermal growth factor receptor 2 (HER2) is the predictive marker and molecular target of anti-HER2 therapies such as the humanized monoclonal antibodies trastuzumab and pertuzumab and tyrosine kinase inhibitors, including lapatinib. The clinical benefit of trastuzumab in HER2-positive breast cancer patients, as defined by immunohistochemical and/or fluorescence in situ hybridization (FISH) analysis, has been widely demonstrated; however, primary and in particular secondary resistance to these treatments has been documented in a substantial proportion of these patients. Despite the identification of several mechanisms of resistance to trastuzumab, the development of clinically useful biomarkers to identify the subset of HER2-positive breast cancer patients unlikely to benefit from the current mainstay anti-HER2 therapies has proven challenging, and the predictive markers in the metastatic setting may not be entirely applicable to the adjuvant setting.
HER2-positive breast cancers have been shown to constitute a heterogeneous disease at the molecular level, and the repertoire of somatic genetic alterations in tumors harboring HER2 gene amplification appears to vary according to estrogen receptor (ER) status and potentially according to the “intrinsic” subtypes (5–8). In addition, contrary to the hypothesis that HER2-positive tumors, as defined by immunohistochemistry and/or FISH, would be generally classified as HER2-enriched if they were ER-negative/HER2-positive and of luminal B subtype if they were ER-positive/HER2-positive, several studies have now demonstrated that all intrinsic subtypes can be identified within clinically HER2-positive breast cancers (4,9,10). It should be …
Journal of the National Cancer Institute , éditorial en libre accès, 2017