TY - JOUR
T1 - Mitosis in circulating tumor cells stratifies highly aggressive breast carcinomas
AU - Adams, Daniel L.
AU - Adams, Diane K.
AU - Stefansson, Steingrimur
AU - Haudenschild, Christian
AU - Martin, Stuart S.
AU - Charpentier, Monica
AU - Chumsri, Saranya
AU - Cristofanilli, Massimo
AU - Tang, Cha Mei
AU - Katherine Alpaugh, R.
N1 - Funding Information:
We would like to thank all of the patients who contributed to this study. We also thank O. Makarova for technical support in this manuscript. This work was supported by a Maryland Technology Development Corporation (TEDCO) MTTCF award, grant R01-CA154624 from the National Cancer Institute, grant KG100240 from the Susan G. Komen Foundation, a grant from an Era of Hope Scholar award from the Department of Defense (BC100675), and the US Army Research Office (ARO) and the Defense Advanced Research Projects Agency (DARPA) (W911NF-14-C-0098). The funders had no role in study design, data collection or analysis, decision to publish, or preparation of the manuscript. The content of the information does not necessarily reflect the position or the policy of the US Government.
Publisher Copyright:
© 2016 Adams et al.
PY - 2016
Y1 - 2016
N2 - Background: Enumeration of circulating tumor cells (CTCs) isolated from the peripheral blood of breast cancer patients holds promise as a clinically relevant, minimally invasive diagnostic test. However, CTC utility has been limited as a prognostic indicator of survival by the inability to stratify patients beyond general enumeration. In comparison, histological biopsy examinations remain the standard method for confirming malignancy and grading malignant cells, allowing for cancer identification and then assessing patient cohorts for prognostic and predictive value. Typically, CTC identification relies on immunofluorescent staining assessed as absent/present, which is somewhat subjective and limited in its ability to characterize these cells. In contrast, the physical features used in histological cytology comprise the gold standard method used to identify and preliminarily characterize the cancer cells. Here, we superimpose the methods, cytologically subtyping CTCs labeled with immunohistochemical fluorescence stains to improve their prognostic value in relation to survival. Methods: In this single-blind prospective pilot study, we tracked 36 patients with late-stage breast cancer over 24 months to compare overall survival between simple CTC enumeration and subtyping mitotic CTCs. A power analysis (1-β = 0. 9, α = 0.05) determined that a pilot size of 30 patients was sufficient to stratify this patient cohort; 36 in total were enrolled. Results: Our results confirmed that CTC number is a prognostic indicator of patient survival, with a hazard ratio 5.2, p = 0.005 (95 % CI 1.6-16.5). However, by simply subtyping the same population based on CTCs in cytological mitosis, the hazard ratio increased dramatically to 11.1, p < 0.001 (95 % CI 3.1-39.7). Conclusions: Our data suggest that (1) mitotic CTCs are relativity common in aggressive late-stage breast cancer, (2) mitotic CTCs may significantly correlate with shortened overall survival, and (3) larger and more defined patient cohort studies are clearly called for based on this initial pilot study.
AB - Background: Enumeration of circulating tumor cells (CTCs) isolated from the peripheral blood of breast cancer patients holds promise as a clinically relevant, minimally invasive diagnostic test. However, CTC utility has been limited as a prognostic indicator of survival by the inability to stratify patients beyond general enumeration. In comparison, histological biopsy examinations remain the standard method for confirming malignancy and grading malignant cells, allowing for cancer identification and then assessing patient cohorts for prognostic and predictive value. Typically, CTC identification relies on immunofluorescent staining assessed as absent/present, which is somewhat subjective and limited in its ability to characterize these cells. In contrast, the physical features used in histological cytology comprise the gold standard method used to identify and preliminarily characterize the cancer cells. Here, we superimpose the methods, cytologically subtyping CTCs labeled with immunohistochemical fluorescence stains to improve their prognostic value in relation to survival. Methods: In this single-blind prospective pilot study, we tracked 36 patients with late-stage breast cancer over 24 months to compare overall survival between simple CTC enumeration and subtyping mitotic CTCs. A power analysis (1-β = 0. 9, α = 0.05) determined that a pilot size of 30 patients was sufficient to stratify this patient cohort; 36 in total were enrolled. Results: Our results confirmed that CTC number is a prognostic indicator of patient survival, with a hazard ratio 5.2, p = 0.005 (95 % CI 1.6-16.5). However, by simply subtyping the same population based on CTCs in cytological mitosis, the hazard ratio increased dramatically to 11.1, p < 0.001 (95 % CI 3.1-39.7). Conclusions: Our data suggest that (1) mitotic CTCs are relativity common in aggressive late-stage breast cancer, (2) mitotic CTCs may significantly correlate with shortened overall survival, and (3) larger and more defined patient cohort studies are clearly called for based on this initial pilot study.
KW - Blood based biopsy
KW - Breast cancer cell motility
KW - Circulating tumor cells
KW - Mitotic index of CTCs
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U2 - 10.1186/S13058-016-0706-4
DO - 10.1186/S13058-016-0706-4
M3 - Article
C2 - 27142282
AN - SCOPUS:85008661393
SN - 1465-5411
VL - 18
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - 44
ER -