Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients

Costanza Paoletti; Meredith M. Regan; Samuel M. Niman; Emily M. Dolce; Elizabeth P. Darga; Minetta C. Liu; P. Kelly Marcom; Lowell L. Hart; John W. Smith; Karen L. Tedesco; Eitan Amir; Ian E. Krop; Angela M. DeMichele; Pamela J. Goodwin; Margaret Block; Kimberly Aung; Martha E. Brown; Robert T. McCormack; Daniel F. Hayes

doi:10.1038/s41523-021-00281-1

Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients

Costanza Paoletti, Meredith M. Regan, Samuel M. Niman, Emily M. Dolce, Elizabeth P. Darga, Minetta C. Liu, P. Kelly Marcom, Lowell L. Hart, John W. Smith, Karen L. Tedesco, Eitan Amir, Ian E. Krop, Angela M. DeMichele, Pamela J. Goodwin, Margaret Block, Kimberly Aung, Martha E. Brown, Robert T. McCormack, Daniel F. Hayes

Medical Oncology

Research output: Contribution to journal › Article › peer-review

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’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.

Original language	English (US)
Article number	77
Journal	npj Breast Cancer
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41523-021-00281-1
State	Published - Dec 2021

ASJC Scopus subject areas

Oncology
Radiology Nuclear Medicine and imaging
Pharmacology (medical)

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10.1038/s41523-021-00281-1

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Paoletti, C., Regan, M. M., Niman, S. M., Dolce, E. M., Darga, E. P., Liu, M. C., Marcom, P. K., Hart, L. L., Smith, J. W., Tedesco, K. L., Amir, E., Krop, I. E., DeMichele, A. M., Goodwin, P. J., Block, M., Aung, K., Brown, M. E., McCormack, R. T., & Hayes, D. F. (2021). Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients. npj Breast Cancer, 7(1), Article 77. https://doi.org/10.1038/s41523-021-00281-1

Paoletti, C, Regan, MM, Niman, SM, Dolce, EM, Darga, EP, Liu, MC, Marcom, PK, Hart, LL, Smith, JW, Tedesco, KL, Amir, E, Krop, IE, DeMichele, AM, Goodwin, PJ, Block, M, Aung, K, Brown, ME, McCormack, RT & Hayes, DF 2021, 'Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients', npj Breast Cancer, vol. 7, no. 1, 77. https://doi.org/10.1038/s41523-021-00281-1

@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 = "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",

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number = "1",

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TY - JOUR

T1 - Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients

AU - Paoletti, Costanza

AU - Regan, Meredith M.

AU - Niman, Samuel M.

AU - Dolce, Emily M.

AU - Darga, Elizabeth P.

AU - Liu, Minetta C.

AU - Marcom, P. Kelly

AU - Hart, Lowell L.

AU - Smith, John W.

AU - Tedesco, Karen L.

AU - Amir, Eitan

AU - Krop, Ian E.

AU - DeMichele, Angela M.

AU - Goodwin, Pamela J.

AU - Block, Margaret

AU - Aung, Kimberly

AU - Brown, Martha E.

AU - McCormack, Robert T.

AU - Hayes, Daniel F.

PY - 2021/12

Y1 - 2021/12

N2 - 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’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.

AB - 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’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.

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Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients

Abstract

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