Abstract 3707: Characterization of estrogen receptor expression on CTCs during CDK4/6i treatment in HR+/HER2- metastatic breast cancer: Results from the PACE phase II study

Cancer Research(2024)

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Abstract Background Circulating tumor cells (CTCs) are associated with worse survival in metastatic breast cancer (MBC). The PACE study (NCT03147287) enrolled patients (pts) with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) MBC after progression on CDK4/6 inhibitor (CDK4/6i) and endocrine therapy, and randomized pts to fulvestrant (ful) alone; ful with palbociclib; or ful, palbociclib, and avelumab [Mayer et al., SABCS 2022]. Pts with ≥5 CTCs appear to derive benefit from treatment combinations vs ful alone. In this feasibility analysis, we evaluated estrogen receptor (ER) expression on CTCs to further investigate their monitoring/predictive potential.Methods Blood samples were collected from pts enrolled in the PACE study at: baseline (T1), first tumor assessment (T2) and progression (T3). CTCs were enumerated using the CellSearch platform and samples were classified as CTChigh or CTClow (cutoff ≥5 CTCs). CTChigh samples underwent ER expression quantification with the ACCEPT software [Zeune et al. 2017]. ER expression intensity (ERint) was measured through the Marker Characterization function for each CTC; the average was calculated for each sample. Results From the 220 enrolled pts, a total of 409 samples (166, 153 and 90 collected at T1, T2, and T3, respectively) were analyzed for ER. Overall, 236 samples were CTClow (T1 = 91, T2 = 97, T3 = 48) and 173 were CTChigh (T1 =75, T2 =56, T3 =42). ER was quantified on 3928, 1853, and 2209 CTCs collected at T1, T2, and T3, respectively. Overall, 32.2% of CTCs were ER negative (ER-).The samples’ median ERint showed a numerical decrease from T1 to T3 (T1 = 7.27, T2 = 4.58, T3 = 1.31). Similarly, the % of ER positive (ER+) CTCs per sample decreased from baseline to progression: 26.3%, 14.0%, 5.5% at T1, T2, T3, respectively.CTChigh samples were then classified as ER+ or ER- (ER+ = mean ER_int >0). At T1, 91 (54.8%) samples were CTClow, 67 (40.4%) were CTChigh/ER+, and 8 (4.8%) were CTChigh/ER-. At progression, 48 (53.3%) samples were CTClow, 26 (28.9%) were CTChigh/ER+, and 16 (17.8%) samples were CTChigh/ER-. A numerical increase in the proportion of CTChigh/ER- samples was thus observed from baseline to progression (4.8 to 17.8%).Conclusions Herein we demonstrated the feasibility of evaluating and quantify ER expression on CTCs with a software-assisted approach to reduce inter-operator variability. In the PACE study, ER expression on CTCs was decreased at progression compared to baseline, possibly suggesting a mechanism associated with treatment resistance. Future analyses are needed to investigate the correlation between ER expression levels on CTCs with survival and treatment response. This, together with information about the mutational status of ESR1 by ctDNA sequencing, might provide a new perspective on the development of resistance to ful and CDK4/6i in HR+/HER2- MBC. Citation Format: Mara Serena Serafini, Carolina Reduzzi, Lorenzo Gerratana, Rinath Jeselsohn, Reshma L. Mahtani, Cynthia X. Ma, Angela DeMichele, Jane Lowe Meisel, Kathy D. Miller, Yara Abdou, Elizabeth C. Riley, Rubina Qamar, Priyanka Sharma, Sonya Reid, Harold J. Burstein, Sara M. Tolaney, Michelle K. DeMeo, Yuan Liu, Eric Gauthier, Yue Ren, Meredith M. Regan, Huiping Liu, Erica L. Mayer, Massimo Cristofanilli. Characterization of estrogen receptor expression on CTCs during CDK4/6i treatment in HR+/HER2- metastatic breast cancer: Results from the PACE phase II study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3707.
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