@article{009321609db84bcc8a3c261047fb61ea,
title = "Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients",
abstract = "Circulating tumor cells (CTC) are prognostic in metastatic breast cancer (MBC). The CTC-endocrine therapy index (CTC-ETI), consisting of CTC-ER (estrogen receptor), BCL2, human epidermal growth factor receptor (HER2), and Ki67 expression, might predict resistance to endocrine therapy (ET) in patients with ER-positive MBC. One hundred twenty-one patients with ER-positive/HER2-negative MBC initiating a new ET after ≥1 lines of ET were enrolled in a prospective, multi-institutional clinical trial. CTC-ETI and clinical/imaging follow-up were performed at baseline and serial time points. Progression-free survival (PFS) and rapid progression (RP; determined at the 3-month time point) were primary endpoints. Associations with clinical outcomes used logrank and Fisher{\textquoteright}s exact tests. At baseline, 36% (38/107) of patients had ≥5 CTC/7.5 ml whole blood (WB). Patients with ≥5 vs. <5 CTC/7.5 ml WB had significantly worse PFS (median 3.3 vs. 5.9 months, P = 0.03). Elevated CTC at 1 month was associated with even worse PFS (1.9 vs. 5.0 months from the 1-month sample, P < 0.001). Low, intermediate, and high CTC-ETI were observed in 71 (66%), 8 (8%), and 28 (26%) patients, with median PFS of 6.9, 8.5, and 2.8 months, respectively (P = 0.008). Patients with high vs. low CTC and CTC-ETI more frequently experienced RP (CTC: 66% vs. 41%; P = 0.03; CTC-ETI: 79% vs. 40%; P = 0.002). In conclusion, CTC enumeration and the CTC-ETI assay are prognostic at baseline and follow-up in patients with ER-positive/HER2-negative MBC starting new ET. CTC at first follow-up might identify a group of patients with ER-positive MBC that could forego ET, but CTC-ETI did not contribute further.",
author = "Costanza Paoletti and Regan, {Meredith M.} and Niman, {Samuel M.} and Dolce, {Emily M.} and Darga, {Elizabeth P.} and Liu, {Minetta C.} and Marcom, {P. Kelly} and Hart, {Lowell L.} and Smith, {John W.} and Tedesco, {Karen L.} and Eitan Amir and Krop, {Ian E.} and DeMichele, {Angela M.} and Goodwin, {Pamela J.} and Margaret Block and Kimberly Aung and Brown, {Martha E.} and McCormack, {Robert T.} and Hayes, {Daniel F.}",
note = "Funding Information: We thank all patients who participated in this study and the clinicians who treated these patients. This work was supported by Janssen Diagnostics, LLC and Menarini Silicon Biosystems, Inc., the Fashion Footwear Charitable Foundation of New York/ QVC Presents Shoes on Sale{\texttrademark} (D.F.H.), and the National Cancer Institute Cancer Center Support Grant (P30CA046592). The authors designed the study in collaboration with the funder (Janssen Diagnostics, LLC./Menarini Silicon Biosystems, Inc.). The funder collected and managed the data with the authors and reviewed this manuscript prior to submission. Funding Information: The authors declare the following competing interests: C.P. received travel reimbursement and research funding from Menarini Silicon Biosystems, Inc. (MSB) during the conduct of the study; research funding from AstraZeneca, Pfizer, outside the submitted work. C.P. is currently working at EISAI, Inc., but this publication is unrelated to her employment. M.M.R. received research support from Janssen Diagnostics, LLC for this work; research support from Novartis, Pfizer, Ipsen, TerSera, Merck, Pierre Fabre, Roche, AstraZeneca, Bristol-Myers Squibb, Bayer outside of the submitted work; consulting or advisory role to Ipsen/Debiopharm, Bristol-Myers Squibb, and Tolmar Pharmaceuticals. Mayo Clinic has received research funding from Eisai, Genentech, GRAIL, MSB, Merck, Seattle Genetics, and Tesaro; these funds were restricted to specific protocols/projects; M.C.L. has not received any personal remuneration. P.K.M has a consulting/advisory relationship with Genentech/Roche, Merck, Celltrion, and Immunomedics in the past 2 years and serves on the speakers{\textquoteright} bureau for Catamount Medical Education and Clinical Care Options; research funding to Duke from Glycomimetics, Abbvie, Novartis, Genentech/Roche, Veridex (for this study only), Innocrin, AstraZeneca, and Verily/Google Life Sciences; consulting/DSMB with Genentech/Roche. L.L.H. serves on the advisory boards and consults for Novartis, G1 therapeutics, Seattle Genetics, AstraZeneca, and Nanostring all outside of the current work. K.L.T. serves on the speakers{\textquoteright} bureau for Daiichi Sankyo, Immunomedics and advisory boards for Astrazeneca, GSK, Seattle Genetics, and PUMA. E.A. has received personal fees for expert testimony from Genentech/Roche, as well as for consulting from Apobiologix, Sandoz, and Novartis. I.E.K. serves on the advisory board/consults/received honoraria from Bristol Meyers Squibb, Daiichi/Sankyo, Macrogenics, Context Therapeutics, Taiho Oncology, Genentech/Roche, Seattle Genetics, AstraZeneca, Celltrion; institutional research funding/grants from Genen-tech/Roche, Pfizer; serves on the data monitoring board for NOVARTIS, Merck. P.J.G. has received funding from the Breast Cancer Research Foundation and support-in-kind (assays) from EPIC Sciences for CTC research outside of the submitted work. R.T.M. was a paid employee of Johnson and Johnson, the parent company of Janssen Diagnostics, LLC. D.F.H. received clinical and laboratory research support from Janssen Diagnostics, LLC, which supported this study, and more recently from MSB, the commercial vendor of CellSearch{\textregistered}. The University of Michigan (UM) holds patent US 8,790,878 B2 for which D.F.H. is designated as inventor, and that is licensed to MSB with annual royalties paid to UM and D.F.H. Outside the submitted work, D.F.H. holds stock options from InBiomotion, and serves on advisory boards for Cepheid, Freenome, CellWorks, Agendia, Salutogenic, EPIC Sciences, Oncocyte, Bioveca, and L-Nutra and UM has received research funding on his behalf from Merrimack, Eli Lilly, Puma Biotechnology, Pfizer, and AstraZeneca. All remaining authors have declared no competing interests. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1038/s41523-021-00281-1",
language = "English (US)",
volume = "7",
journal = "npj Breast Cancer",
issn = "2374-4677",
publisher = "Nature Publishing Group",
number = "1",
}