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.

Background. Neoadjuvant endocrine therapy (NET) in luminal breast cancer (LBC) is the perfect scenario for real-time evaluation of the biological and molecular changes that occur after estrogenic deprivation. This evaluation is mainly performed in surgical specimens after NET and has been used as a research tool to obtain prognostic and predictive information using tumor response to decide adjuvant treatment. Nevertheless, there are not many validated biomarkers in this setting to predict response beyond Ki67 levels and modified Preoperative Prognostic Index (mPEPI score) after treatment. Hence, the aim of this study is to determine if changes in mRNA-based PAM50 analysis (intrinsic subtype) after NET in LBC correlate with such biomarkers. Methods. We collected a series of postmenopausal ER+/HER2- breast cancer patients (n=58) treated for at least 4 months with NET before surgery. Next, we performed gene expression analysis by PAM50 accompanied by pathological characterization of surgical tumor specimens and immunohistochemistry characterization of ER and Ki67 levels, both at diagnosis and in surgery specimen. Finally, we studied the association of our results with clinical and histopathological features and with validated biomarkers for endocrine response, such as mPEPI score and changes in Ki67 levels. Results. The distribution of changes in intrinsic subtype determined by PAM50 after NET is presented in Table 1. We observed that tumors that changed from luminal to a normal intrinsic subtype showed larger changes in Ki67 levels after NET and reduced percentage of Ki67 positive cells at surgery, compared to those that presented a luminal persistent status: both analysis P<0.0001 (Mann-Whitney test). Similarly, we found a statistical association between lower mPEPI score in those tumors that change from luminal to a normal intrinsic subtype compared to those that presented a luminal persistent status: P=0.0034 (Mann-Whitney test). Moreover, in agreement with these results, we also studied ROR-P (PAM50 risk of recurrence (ROR) of subtype plus proliferation) in tumors that change from luminal to a normal intrinsic subtype and in those that presented a luminal persistent status. Results showed the same trends as the ones observed for Ki67-related parameters and mPEPI. Conclusions. PAM50 analysis revealed that changes from luminal A and luminal B to normal intrinsic subtype are associated with response to NET, measured by different well-established parameters. This result gives us clues to further explore which genes are orchestrating these changes and their impact on clinical outcomes. However, more analyses should be performed to determine the relationship between ROR and parameters used to measure response in NET in order to validate the results presented. In conclusion, our data support that the determination of the changes in gene expression profile using PAM50, before and after NET, can be used as a tool to predict response, conjointly with other clinical parameters. Table 1.- Intrinsic subtypes determined by PAM50 in samples pre and post NETPAM50 PREPAM50 POSTNO.%PERSISTANT LUMINAL STATUSCHANGE FROM LUMINAL TO A NOLMAL INTRINSIC SUBTYPELumALumA2136YESLumANormal1526YESLumALumB35YESLumBLumA610YESLumBNormal35YESLumBLumB59YESHER2HER223NANAHER2LumA12NANALumAHER212NANANormalNormal12NANATOTAL58100Lum=LuminalNA= Not applicable Citation Format: Joanna Ines Lopez Velazco, María Otaño, Inazio Lacambra, Kepa Elorriaga, Ainhara Lahuerta, Ana Martínez, Virginia Segur, Sara Manzano, Aleix Prat, María Caffarel, Ander Urruticoechea. Conversion from luminal to normal intrinsic subtype by PAM50 after neoadjuvant endocrine therapy is associate with biomarkers of good prognosis in luminal breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-15-01.

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