Genetics, RNA subtype, and tumor microenvironment are clinically important and independently predictive of trastuzumab response when examining the tumor in a patient with HER2-positive breast cancer, according to a study to be presented at the San Antonio Breast Cancer Symposium 2016 meeting.1

Researchers led by Maki Tanioka, PhD, of the University of North Carolina in Chapel Hill conducted genomic analyses on pathologic complete response (pCR) of 213 pre-treatment tumors. pCR was defined as having no invasive tumor in the breast of observed patients.

Through mRNAseq and DNA exome sequencing, they examined clinicopathological information as well as somatic mutation status. They derived 422 segment-level DNA Copy Number Alterations and 510 gene expression signatures.

The researchers found that while clinical estrogen/progesterone receptor (ER/PgR) status as well as intrinsic subtype by PAM50 were associated with pCR, stage of the disease and paclitaxel and trastuzumab therapy either with or without lapatinib were not associated with pCR.

Models that utilized gene signatures or DNA Copy Number Alterations were found to be more predictive of response upon Elastic Net analysis, compared to models that used mutation status.

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The authors concluded that Copy Number Alterations, HER2-enriched and Luminal status, as well as immune cell features were predictive of response to treatment with trastuzumab.

Reference

  1. Tanioka M, Fan C, Carey LA, et al. Integrated analysis of multidimensional genomic data on CALGB 40601 (Alliance), a randomized neoadjuvant phase III trial of weekly paclitaxel (T) and trastuzumab (H) with or without lapatinib (L) for HER2-positive breast cancer. Paper to be presented at: 2016 San Antonio Breast Cancer Symposium (SABCS); December 6-10, 2016; San Antonio, TX.