Transcriptional expression of 8 genes predicts pathological response to first-line docetaxel + trastuzumab-based neoadjuvant chemotherapy

Abstract

BackgroundOverexpression of HER2 is observed in 20 to 30% of breast carcinomas. The use of trastuzumab has improved the treatment of these patients, especially when it is associated with docetaxel. To optimize the use of this treatment, it seems important to select putative complete responders before treatment administration.MethodsIn this study, we analyzed by quantitative PCR the expression of 28 genes in HER2-overexpressing tumors treated with trastuzumab + docetaxel-based chemotherapy. We then correlated their expression profile with those of trastuzumab-sensitive and resistant cell lines to classify tumors as having a sensitive (pCR) or resistant (non-pCR) profile. Finally, we used public datasets from the GEO website to validate the reduced gene-expression profile obtained.ResultsWe identified an 8-gene-expression combination that predicted the response to treatment with an accuracy of 76%. Based on public microarray data, we showed that the expression profile was specific to first-line trastuzumab + docetaxel-based treatment with an accuracy of 85%.ConclusionsOur results showed that by profiling the expression of 8 genes it was possible to predict the response to first-line trastuzumab + docetaxel-based chemotherapy. The use of cancer cell lines as the reference allowed a proper fit with the specificity of different tissues, such as lung or gastric cancers, which could also be eligible to concomitant HER2 inhibition by treatment with trastuzumab or tyrosine kinase inhibitors and docetaxel.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1198-9) contains supplementary material, which is available to authorized users.

HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology

“…112 Gene expression profiling using eight transcripts has been shown to predict response to trastuzumab-and docetaxel-based chemotherapy in GEA with HER2 overexpression. 113 Multiplex ligation-dependent probe amplification is a multiplex PCR technique that simultaneously quantifies several gene segments. This technique can be used to interpret whether the HER2 region of the chromosome is amplified compared with control regions of chromosome 17.…”

HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology

“…112 Gene expression profiling using 8 transcripts has been shown to predict response to trastuzumab-and docetaxel-based chemotherapy in GEA with HER2 overexpression. 113 Multiplex ligation-dependent probe amplification is a multiplex PCR technique that simultaneously quantifies several gene segments. This technique can be used to interpret whether the HER2 region of the chromosome is amplified compared to control regions of chromosome 17.…”

Preoperative Chemotherapy for Gastric Cancer: Personal Interventions and Precision Medicine

“…Overexpression of FoxM1 also enhanced resistance to docetaxel. Schmitt et al [44] showed that the transcriptional expression of eight genes predicted pathological response to docetaxel combined with trastuzumab-based preoperative chemotherapy.…”