Abstract P4-04-05: Primary endocrine therapy (PETx) induces PAM50 intrinsic subtype migration with prognostic implications
Authors: Larburu L , Paré L , Rezola R , Carrera M , Buch E , Gimenez J , Quiroga V , Fernandez M , Aragón S , Pascual T , Prat A , Urruticoechea A 
Published: February 2018

Backgorund: ER activation is a major ruler of cell biology in ER+ve breast cancer. Hence, ER dependent gene expression at diagnosis, may unveil most of the oncogenic mechanisms responsible of potential tumour relapse and metastasis. Thus, we hypothesized that oestrogen deprivation through PETx may unveil underlying tumour biology with deeper prognostic implications. To explore this, we studied changes in PAM50 intrinsic subtyping and Risk of Recurrence score throughout PETx and their correlation with known prognostic factors.

Methods: Clinical-pathological data were evaluated in a series of patients with stage I-III ER-positive/HER2-negative breast cancer treated in 6 centers in Spain with PETx during more than two months with available baseline and surgical samples. The expressions of 50 genes were measured in baseline samples and surgical specimens using the nCounter platform. Intrinsic subtypes and Risk of Recurrence score (ROR) were determined by the research-based PAM50 predictor. Response by ultrasonography (US) and magnetic resonance (RMI) between diagnosis and before surgery and PEPI score in surgical samples were used as the endpoints. Association between two variables was evaluated using χ2 test or Pearson correlation. All statistical tests were two-sided and considered significant when P≤0.05.

Results: Gene expression profile was feasible in 58 pre/post sample pairs with a median of 7.8 months (range 2.5-40.6) of PETx with AIs (98.3%) or tamoxifen (1.7%). At baseline, 68.9%(n=40) were classified as Luminal A, followed by Luminal B (24.1%; n=14), HER2 enriched (HER2-E) (5.2%; n=3) and Normal-like (1.8%; n=1). Radiologic response did not change significantly according to intrinsic subtype either by MRI or US (P&gt;0.05). Instead, PEPI score varied according to intrinsic subtype (P=0.024).Thirteen (32%) of LumA, while neither of LumB or HER2-E tumours showed a PEPI score Group 1. PETx resulted in changes in the intrinsic subtype in 29 (50%) of tumours

Table 1 Her2-E postLumA postLumB postNormal postHer2 pre2 (66.7%)1 (33.33%)00LumA pre1 (2.5%)21 (52.5%)3 (7.5%)15 (37.5%)LumB pre06 (42.86%)5 (35.71%)3 (21.43%)Normal pre0001 (100%)

. Of note, 2 of 3 (66.7%) HER2 tumors, and 5 of 14 (35.7%) LumB tumors did not change their profile. Forty-eight (83%) tumours showed a decrease in ROR score after PETx (P&lt;0.001). ROR was over 30 in 29 tumours (49.1%) at baseline and 16 (27%) at surgery. Change in ROR was moderately correlated with percentage of change in Ki-67 [correlation: 0.417 (P&lt;0.01)]. Correlation of surgical tumour subtype with IHC markers of cell-viability/apoptosis will be presented.

Conclusion: Oestrogen deprivation of luminal tumours through PETx results in profound changes in tumour biology including a migration in intrinsic subtype in 50% of tumours.

Correlation of the largely decreased ROR with changes in Ki67 reveals the potential prognostic additional information generated by profiling tumours after PETx. ER-blockade may unveil underlying tumour oncogenic capabilities for relapse, survival and metastasis.

Hence, the post-PETx gene expression profile, molecular subtype and ROR may bear incremental prognostic and predictive information generating a novel scenario for optimal clinical decision making.

Citation Format: Larburu L, Paré L, Rezola R, Carrera M, Buch E, Gimenez J, Quiroga V, Fernandez M, Aragón S, Pascual T, Prat A, Urruticoechea A. Primary endocrine therapy (PETx) induces PAM50 intrinsic subtype migration with prognostic implications [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-04-05.