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>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<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<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.

Background: Neoadjuvant endocrine therapy (NET) is an approach that allows real-time evaluation of drug efficacy as well as investigation of the biological and molecular changes that occur after estrogenic deprivation. This evaluation is mainly performed in surgical specimens after NET and it has been used as a research tool to obtain prognostic and predictive information using tumour response to decide adjuvant treatment. In this setting, there are not many validated biomarkers to predict response beyond Ki67 expression and Preoperative Prognostic Index (PEPI score) in NET. The aim of this study is to determine if the tumour cellularity size (TCS) in surgical specimen after NET correlates with PEPI score and Ki67 expression. Methods: Retrospective study of postmenopausal patients with estrogen receptor (ER) positive/HER2 negative resectable breast cancer, treated with an aromatase inhibitor for at least 4 months prior to surgery. Pathological characterization of tumour specimens: Evaluation of the percentage of residual tumour cellularity of formalin fixed paraffin embedded surgical specimens and immunohistochemistry characterization of ER and Ki67. Tumour cellularity size: calculated by combining the percentage of residual tumour cellularity and tumour pathological size. Results: N=104. Tumour characteristics at surgery and breakdown for the calculated PEPI score: table 1. Correlation between the percentage of Ki67 positive cells at surgery and TCS: (r=0.2503) p=0.04 (95% CI, 0.0014 to 0.4700). Correlation between TCS and PEPI score: (r=0.2582) p=0.05 (95% CI, -0.0131 to 0.4940). Conclusions: Tumour cellularity size is a promising biomarker to determine response and prognosis after NET. There is a need to find other biomarkers to predict response after NET. Table 1Pathology/Biomarker statusPEPI score RFS pointsNo. of patientspTNot available (NA)1pT1/T20102pT3/T431pNNA7Negative075Positive322KI67 levelNA10%-2.7%039>2.7%-7.3%131>7.3%-19.7%119>19.7%-53.1%213>53.1%31ER-status Allred scoreNA120-2303-8092PEPI scoreNA190281342533495561PEPI groupNot calculated19I (0 score)28II (1-3 score)42III (≥4 score)15 Citation Format: Joanna Ines Lopez Velazco, María Otaño, Lide Larburu, Ainhara Lahuerta, Kepa Elorriaga, Virginia Segur, Juan Carlos Irizabal, Ana Martínez, Lourdes Jáuregui, Maria M. Caffarel, Ander Urruticoechea. Tumour cellularity size as a biomarker to predict response after neoadjuvant endocrine therapy: Correlation analysis between Ki67 expression and PEPI score [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-39.

Background: Apatinib is an orally administered small-molecular receptor tyrosine kinase inhibitor (TKI) with potential antiangiogenic and antineoplastic activities. This study was conducted to assess efficacy and safety of lower-dose apatinib combined with nanoparticle albumin-bound paclitaxel (nab-p) and carboplatin as a neoadjuvant regimen for triple negative breast cancer (TNBC).Methods: This single arm study enrolled patients with operable TNBC. Patients received apatinib (250mg, po, d1-21), nab-p (260mg/m 2 , ivgtt, d1) concurrently with carboplatin (AUC¼5-6, ivgtt, d1) for 6 cycles, each 21-day cycle, followed by surgery. The primary endpoint was pathological complete response (pCR) rates, defined as no invasive or noninvasive tumor residuals in both breast and axillary lymph nodes (ypT0 ypN0), or no invasive tumor residuals in the breast, and no invasive or noninvasive tumor residuals in the axillary lymph nodes (ypT0/is ypN0). Secondary endpoints included objective response rate (ORR), disease free survival (DFS), overall survival (OS), and toxicity.Results: 18 female patients with a median age of 45 years (20-62 years) were enrolled from Sep. 22, 2018 to Dec. 24, 2019. All the 18 pts completed neoadjuvant chemotherapy followed by surgery, however, only 1 patient did not provide enough data for efficacy evaluation. Rates of ypT0 ypN0 and ypT0/is ypN0 were 35.2% (6/17) and 41.2% (7/17), respectively. ORR was 94.1% (16/17). DFS and OS had not been evaluated since short time follow-up. 8 pts experienced apatinib-related dose discontinuation during treatment. Carboplatin induced myelosuppression was the main reason of chemotherapy delay. The most common grade 3/4 treatment-related adverse events (AEs) were thrombocytopenia (11/18), anaemia (10/18), neutropenia (7/18) and hypertension (3/18). Adverse events were well controlled after drug discontinuation and dose adjustment. No treatment-related death was occurred.Conclusions: This neoadjuvant regimen, apatinib combined with nab-p and carboplatin, exhibited acceptable efficacy and manageable toxicity in neoadjuvant treatment of TNBC pts. Long-time follow-up are still needed.Clinical trial identification: NCT03650738.

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