PD05-03: Impact of Quantitative Measurement of HER2, HER3, HER4, EGFR, ER and PTEN Protein Expression on Benefit to Adjuvant Trastuzumab in Early-Stage HER2+ Breast Cancer Patients in NCCTG N9831.

Perez, EA; Ballman, KV; Reinholz, MM; Dueck, A. C.; Cheng, Hao; Jenkins, RB; McCullough, AE; Chen, B; Davidson, NE; Martino, S; Kaufman, PA; Kutteh, LA; Sledge, G. W.; Geiger, XJ; Jn, Ingle; Tenner, K.; Harris, L; Gralow, JR; Rimm, DL

doi:10.1158/0008-5472.sabcs11-pd05-03

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“…Analysis of their samples failed to demonstrate a link between increased disease-free survival and cMYC, 6 ERBB3, or PTEN. 7,8 Preliminary analyses have been presented from several clinical trials that addressed the role of PI3K mutations in HER2-positive breast cancer in the adjuvant, metastatic, and neoadjuvant settings. 9,10 Although the preliminary findings are not invariably consistent in these trials, the data suggest that such mutations may be prognostic but are not predictive of benefit from HER2-targeted therapy.…”

Section: Introductionmentioning

confidence: 99%

Genomic Analysis Reveals That Immune Function Genes Are Strongly Linked to Clinical Outcome in the North Central Cancer Treatment Group N9831 Adjuvant Trastuzumab Trial

Perez

Thompson

Ballman

et al. 2015

JCO

174

137

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Purpose To develop a genomic signature that predicts benefit from trastuzumab in human epidermal growth factor receptor 2–positive breast cancer. Patients and Methods DASL technology was used to quantify mRNA in samples from 1,282 patients enrolled onto the Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer (North Central Cancer Treatment Group N9831 [NCCTG-N9831]) adjuvant trastuzumab trial. Cox proportional hazard ratios (HRs), adjusted for significant clinicopathologic risk factors, were used to determine the association of each gene with relapse-free survival (RFS) for 433 patients who received chemotherapy alone (arm A) and 849 patients who received chemotherapy plus trastuzumab (arms B and C). Network and pathway analyses were used to identify key biologic processes linked to RFS. The signature was built by using a voting scheme. Results Network and functional ontology analyses suggested that increased RFS was linked to a subset of immune function genes. A voting scheme model was used to define immune gene enrichment based on the expression of any nine or more of 14 immune function genes at or above the 0.40 quantile for the population. This model was used to identify immune gene–enriched tumors in arm A and arms B and C. Immune gene enrichment was linked to increased RFS in arms B and C (HR, 0.35; 95% CI, 0.22 to 0.55; P < .001), whereas arm B and C patients who did not exhibit immune gene enrichment did not benefit from trastuzumab (HR, 0.89; 95% CI, 0.62 to 1.28; P = .53). Enriched immune function gene expression as defined by our predictive signature was not associated with increased RFS in arm A (HR, 0.90; 95% CI, 0.60 to 1.37; P = .64). Conclusion Increased expression of a subset of immune function genes may provide a means of predicting benefit from adjuvant trastuzumab.

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Section: Introductionmentioning

confidence: 99%