Abstract P4-08-07: Discordance between surrogated intrinsic subtypes defined by immunohistochemistry compared with PAM50 in ER positive / HER2 negative early breast cancer. Analysis of value of the status of the progesterone receptor and Ki67
Authors: Rodriguez CA , Guillen C , Garcia M , Sancho M , Gomez A , Ludena D , Cruz JJ 
Published: May 2019

Introduction: Classification by intrinsic subtypes by gene expression profiles of early-stage breast cancer (EBC) provides information of prognostic value and constitutes a tool to help in making therapeutic decisions. Several authors have proposed surrogated classifications based on immunohistochemistry results (IHC) in order to facilitate a classification with identical prognostic and predictive value. However, there is evidence that suggests a lack of correlation between these classifications.

The aim of this study was to evaluate the correlation between classification by intrinsic subtypes in patients with EBC ER+/ HER2neg, obtained by PAM50 and the surrogated classification proposed by St. Gallen 2013.

Methods: Samples from 12 centers from the spanish region of Castilla y León were analyzed by PAM50 (nCounterTM / Nanostring) at the University Hospital of Salamanca. The results obtained were compared with the surrogate classification of St.Gallen'13 from local reports. Tumors of patients pre and post-menopausal tests T1-2, N0-N1mi, grade I-II that met criteria for inclusion of the regional evaluation program through ProsignaTM were included.

Results: Between August'15 and December'17, 264 samples were analyzed. All patients were classified by IHC as lum-A or lum-B. In total 113 cases were reclassified by PAM50 (43%). The change of LumA by IHC to Lum-B by PAM50 was 18%, while Lum-B by IHC to Lum-A by PAM50 was 58% (n = 89). In those cases considered Lum-B by IHC based only in a value of Ki67&gt;14% (n = 93), 54% was reclassified to Lum-A. Conversely, when low expression (negative or &lt;20%) of Progesterone Receptor (PR) was used as the single criterion of Lum-B by IHC (n = 44), PAM50 reclassified 33 cases as Lum-A (75%). Applying the Kappa test to analyze the concordance between the 2 tests, a coefficient of 0.203 (low agreement) was obtained, statistically significant (0.000).

Conclusion: The surrogated classification by IHC of intrinsic subtypes in EBC ER+/HER2neg shows a low concordance with PAM50 analysis, and cannot be considered adequate. In particular, the presence of negative or &lt;20% PR as the only criterion seems the least appropriate and should not be recommended for a surrogated classification of a tumor as Lum-B, overestimating the real risk of numerous patients. PAM50 allowed the reclassification in more than 40% of cases, especially csaes considered Lum-B by IHC.

Citation Format: Rodriguez CA, Guillen C, Garcia M, Sancho M, Gomez A, Ludena D, Cruz JJ. Discordance between surrogated intrinsic subtypes defined by immunohistochemistry compared with PAM50 in ER positive / HER2 negative early breast cancer. Analysis of value of the status of the progesterone receptor and Ki67 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-07.