Abstract P2-15-01: Conversion from luminal to normal intrinsic subtype by PAM50 after neoadjuvant endocrine therapy is associate with biomarkers of good prognosis in luminal breast cancer
Authors: Joanna Ines Lopez Velazco, María Otaño, Inazio Lacambra, Kepa Elorriaga, Ainhara Lahuerta, Ana Martínez, Virginia Segur, Sara Manzano, Aleix Prat, María Caffarel, Ander Urruticoechea
Journal: Cancer Research (2022)

Abstract 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&amp;lt;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.