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Breast cancers, both early and advanced, are heterogeneous causing differential responses to targeted therapy. Explosion in targeted treatment choices requires real time assessment of tumor characteristics in patients initially and over time. A dynamic detection system, not a static pathology specimen, is required for continuous profiling while treatment changes; hence, the interest in circulating tumor cells (CTCs). Our novel QCDx br™ system analyzes all nucleated cells from a blood sample aliquot, morphologically intact and immobilized in hydrogel, after multiplex, immunofluorescent (IF) staining. We characterize increased numbers of CTCs (nucleated, CD45-negative cells) as single cells, in clusters and in connection with circulating inflammatory cells, stained with two, separate IF marker cocktails, denoting (1) epithelial (EpCAM, Cytokeratin CK), mesenchymal (Vimentin VIM) phenotypes and (2) therapeutic HER2, ER and TROP2 targets which are the basis for targeted therapy in breast cancer. In the ongoing, prospective CLINBREAC trial, we enrolled to date 9 neoadjuvant (early stage, ES) and 21 metastatic (late stage, LS) breast cancer patients, collecting 7.5 ml of blood at 3-month intervals or at change of therapy. We are now out over 2 years with the earliest ES and LS patients showing changes in CTCs with disease progression and in response to treatment, often pre-dating changes seen in follow up biopsies. Detection of HER2+ CTCs was of particular interest in patients with HER2 low cancers¬ (1+ or 2+). Results presented here, contain the more complete datasets from 8 ES and 11 LS patients. QCDx br™ detected CTCs in all 19 Stage I-IV patients that could exceed 100 CTCs/2500 nucleated cells in LS and 50 CTCs/2500 nucleated cells in ES patients. The table shows count averages of CTCs/2500 nucleated cells detected by different IF markers. Of note, CTCs showed combinations of IF markers (hybrid cells). For example, CTCs expressed both VIM and CK indicating epithelial to mesenchymal transition (EMT) phenotype, which may signify higher metastatic potential. ER+ CTC were seen in LS, not ES patients. All ES patients including those with HER2 low tumors, showed HER2+ CTCs. Of note, not included in the table are two, triple-positive patients with oligo-metastatic disease now 4 and 10 years out from diagnosis without evidence of disease and on maintenance HER2 and ER-directed therapy. No CTCs are seen at their first data point. We were unable to detect CTCs in 13 healthy volunteers. In ES patients, CTC numbers did not associate with tumor size, nodal involvement, ER or HER2 status. For example, one TNBC patient with a T3 tumor and positive nodes had some of the lowest numbers of CTCs. The more complete quantification of the LS patients is in process. As development of QCDx br™ continues, multiplex IF staining of 12+ markers per CTC and identification of single CTC mutational changes is expected. This powerful technology enables targeted treatment decisions with specific drugs resulting in maximal responses. Average CTC counts/2500 nucleated cells detected by phenotypic and therapeutic IF cocktails Citation Format: Susan Tannenbaum, Emily Hsu, jasmin Hundal, Amber Wilkes, Austin Fergusson, Fahmy Mamuya, Triantafyllos Tafas. Targeting treatment to tumor response: demonstration of response monitoring with subsequent impact on treatment choices in real time utilizing a novel technology [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-05-09. |
