Abstract P1-03-04: Concordance of local immunohistochemistry with TargetPrint microarray based assessment of ER, PR and Her2 and BluePrint molecular subtyping in the Symphony Triple A study
Authors: Kuijer A , Straver M , Elias S , Smorenburg C , Wesseling J , Linn S , Rutgers E , Siesling S , van Dalen T 
Published: March 2017

PURPOSE: A decade ago intrinsic biological breast cancer subtypes have been identified which have proven to be of clinical importance in terms of outcome and response to systemic treatment. The aim of the current study is to assess concordance between breast cancer subtypes determined by local immunohistochemistry (IHC) assessment of estrogen receptor (ER), progesterone receptor (PR) and Her2-receptor status and microarray based molecular subtyping in a subset of ER+ early stage breast cancer patients.

PATIENTS AND METHODS: In this prospective observational multicenter study information on local pathology assessment and BluePrint/TargetPrint results were obtained in ER+ Dutch early stage breast cancer patients in whom a 70-gene profile (MammaPrint) was used as they were enrolled in clinical trial based on the existence of controversy regarding the additional value of adjuvant CT. Local IHC assessment of ER, PR and Her2 status were compared with microarray based assessment (TargetPrint/BluePrint) of these characteristics. Reclassification of ER and PR overexpression was assessed by a McNemars test and by Spearman correlation. Furthermore, concordance between the clinical subtypes based on local pathology (Luminal-type: ER+/PR+/Her2-; Her2-type: Her2+ disease) and molecular subtyping was assessed.

RESULTS: Between January 2013 And December 2015 660 patients, treated in 31 hospitals, were enrolled. In 564 (85%) BluePrint and/or TargetPrint was performed in addition to the 70-GS. The majority of patients had ER+/Her2- disease and TargetPrint reclassified 1% (n = 7) of patients as ER-negative (r = 0,250, p &lt;0,001). TargetPrint reclassified 7% (n = 40) and 2% (n = 11) of patients for PR and Her2 status respectively (table 1, r = 0,580, p &lt;0,001 for PR

Table 1. Concordance between immunohistochemistry and TargetPrint. TargetPrint result (ER, PR and Her2 resp.)  ImmunohistochemistryPositiveNegativeOverall discordance (%)p-value*Estrogenreceptor status    Positive557 (99%)6 (1%)  Negativen.a.n.a.1%n.a.Progesterone receptor status    Positive474 (96%)18 (4%)  Negative22 (31%)49 (69%)7%0,636Her2 receptor status    Positive3 (30%)7 (70%)  Negative4 (3%)546 (97%)2%0,549Equivocal0 (0%)3 (1%)  * P-value represents results of the McNemar test.). Based on IHC 545 (98%) patients were regarded as luminal-type and the remaining 2% as Her2-type. BluePrint reclassified 2% of the clinical luminal-type patients: 4 (1%) patients were reclassified as basal-type and 3 (0%) patients as Her2-type. Of the clinical Her2-type patients 80% (n=8) was reclassified by BluePrint as molecular luminal-type.

Table 2. Concordance between clinical subtyping and molecular subtyping according to BluePrint.  BluePrint resultClinical SubtypeNo. ptsLuminalBasalHer2Luminal545539 (99%)4 (1%)3 (0%)Her2108 (80%)02 (20%)Note. Overall discordance 3%.

Conclusion: In the current study we observe a high concordance between microarray-based assessment of ER, PR and Her2 and local pathology in Dutch ER+ early stage breast cancer patients. In the small subset of ER+ patients who are considered candidates for 70 GS use and who have HER2+ tumors by IHC molecular typing of HER2 status is of additional value.

Citation Format: Kuijer A, Straver M, Elias S, Smorenburg C, Wesseling J, Linn S, Rutgers E, Siesling S, van Dalen T. Concordance of local immunohistochemistry with TargetPrint microarray based assessment of ER, PR and Her2 and BluePrint molecular subtyping in the Symphony Triple A study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-03-04.