Genomic Instability Predicts Response to Trastuzumab Plus Lapatinib in ER+ Breast Cancer

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A total of 159 recurrent CNA regions were identified. ERBB2 amplification was associated with high pCR, but the association fell to insignificance after correcting for ERBB2 expression.
A total of 159 recurrent CNA regions were identified. ERBB2 amplification was associated with high pCR, but the association fell to insignificance after correcting for ERBB2 expression.
The following article features coverage from the San Antonio Breast Cancer Symposium (SABCS) 2017 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.

Tumor genomic instability predicts for pathological complete response (pCR) among patients receiving trastuzumab plus lapatinib neoadjuvant therapy for some early breast cancer subtypes, according to study findings presented at the 2017 San Antonio Breast Cancer Symposium.1

ERBB2 amplification was predictive of pCR, but ERBB2 mRNA expression and PAM50-enriched HER2 better predicted pCR, reported lead study author Cristos Sotiriou, MD, of the Breast Cancer Translational Research Laboratory at the Institut Jules Bordet in Belgium.1

Copy number alterations (CNAs) were not, however, associated with event-free survival (EFS).

In the phase 3 NeoALTTO trial (ClinicalTrials.gov Identifier: NCT00553358), trastuzumab plus lapatinib for neoadjuvant therapy in patients with early HER2-positive breast cancer “nearly doubled” the pCR rate when compared with anti-HER2 treatment alone.

Dr Sotiriou and colleagues sought to assess whether genomic CNAs are associated with pCR and EFS. They used CytoScan HD arrays to hybridize tumor DNA from 271 patients' tumors from the study. Tumor infiltrating lymphocytes (TILs) and gene expression were also obtained and the genome instability index (GII) was calculated.

A total of 159 recurrent CNA regions were identified. ERBB2 amplification was associated with high pCR (P = .0007), but the association fell to insignificance after correcting for ERBB2 expression.

High genomic instability was associated with higher rate of pCR in the estrogen receptor–positive (ER+)  subgroup of patients, Dr Sotiriou said.

“A novel amplified region on 6q23-24 was shown to be predictive of pCR, in particular for ER+ tumors,” he added. “This may warrant further investigation.”

Read more of Cancer Therapy Advisor's coverage of the San Antonio Breast Cancer Symposium (SABCS) 2017 meeting by visiting the conference page.

Reference

  1. Sotiriou, C, Rothé F, Maetens M, et al. Copy number aberration analysis to predict response to neoadjuvant anti-HER2 therapy: Results from the NeoALTTO phase III trial. Oral Presentation at: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TX.

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