PIK3CA, PAM50 Do Not Predict Adjuvant Trastuzumab Response in HER2-Positive Breast Cancer

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PIK3CA mutation status and PAM50 tumor subtype do not predict poor trastuzumab response in the adjuvant setting.
PIK3CA mutation status and PAM50 tumor subtype do not predict poor trastuzumab response in the adjuvant setting.

SAN ANTONIO—PIK3CA mutation status and PAM50 tumor subtype do not predict poor trastuzumab response in the adjuvant setting, according to analyses of archived tumor blocks from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 trial. The findings were presented at the 2014 San Antonio Breast Cancer Symposium.

Unlike results seen in the metastatic and neoadjuvant clinical trials, PIK3CA and PAM50 intrinsic subtypes did not prove predictive of differential response to trastuzumab. “PAM50 intrinsic subtype or PIK3CA mutation failed to identify subgroups that did not benefit from trastuzumab,” reported senior author Soonmyung Paik, MD, of the NSABP Tissue Bank in Pittsburgh, PA.

The data “suggest that results from the metastatic and neoadjuvant setting may not always be applicable to the adjuvant setting,” Dr. Paik was quick to note. “Response of micrometastatic tumor cells in adjuvant setting may be quite different from metastatic or neoadjuvant setting,” he said, adding that this might be due to the efficacy of trastuzumab against cancer stem cells.

Molecular heterogeneity measured as gene expression and mutations is “considerable” in HER2-positive breast cancer and earlier studies had suggested that PIK3CA mutational status and PAM50 intrinsic tumor subtype are “markers of response to anti-HER2 therapies,” he explained.

The study team therefore hypothesized that among patients with HER2-positive breast cancer, those with non-HER2-enriched intrinsic subtype or PIK3CA mutation do not benefit from trastuzumab. They assessed the predictive value of those two biomarkers in the adjuvant setting, using tumor blocks archived from NSABP trial B-31.

Expression data for 49 genes using the nCounter® platform was used to generate PAM50 intrinsic subtypes for 1,579 archived tumor blocks and PIK3CA mutation assay was successfully completed for 672 patients, Dr. Paik reported.

But trastuzumab-associated disease-free survival rates were similar for both HER2-enriched and non-HER2–enriched tumors (hazard ratios  = 0.44 and 0.47, respectively), and patients with PIK3CA mutation similarly benefited from treatment, Dr. Paik reported.

The study was funded by the National Cancer Institute and the Pennsylvania State Department of Health.

Reference

  1. Paik S, Pogue-Geile KL, Song N et al. S3-05. Presented at: San Antonio Breast Cancer Symposium 2014. Dec. 9-13, 2014; San Antonio, TX.

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