Top

Published in:

01-07-2015 | Research Article

Correlation of hormone receptor status between circulating tumor cells, primary tumor, and metastasis in breast cancer patients

Authors: K. Kalinsky, J. A. Mayer, X. Xu, T. Pham, K. L. Wong, E. Villarin, T. J. Pircher, M. Brown, M. A. Maurer, F. Z. Bischoff

Published in: Clinical and Translational Oncology | Issue 7/2015

Abstract

Purpose

Estrogen receptor (ER) and progesterone receptor (PR) status is prognostic and predictive in breast cancer. Because metastatic breast tumor biopsies are not routinely feasible, circulating tumor cells (CTCs) offer an alternative source of determining ER/PR tumor status.

Methods/patients

Peripheral blood was collected prospectively from 36 patients with metastatic breast cancer. CTCs were isolated using the microfluidic OncoCEE™ platform. Detection was accomplished with an expanded anti-cytokeratin (CK) cocktail mixture and anti-CD45. ER/PR protein expression was assessed by immunocytochemistry (ICC) on the CK+ cells and compared to the primary and/or metastatic tumor by immunohistochemistry (IHC).

Results

Among the 24 CK + CTC cases, a concordance of 68 % (15/22) in ER/PR status between primary breast tumor and CTCs and 83 % (10/12) between metastatic tumor and CTCs was observed. An overall concordance of 79 % (19/24) was achieved when assessing CTC and metastatic tumor (primary tumor substituted if metastatic breast biopsy not available). A test sensitivity of 72 % and specificity of 100 % was identified when comparing CTCs to tumor tissue. Of the 7 discordant cases between CTCs and primary tumor tissue, 2 were concordant with the metastatic biopsy.

Conclusions

CTC ER/PR status using the OncoCEE™ platform is feasible, with high concordance in ER/PR status between tumor tissue (IHC) and CTCs (ICC). The prognostic and predictive significance of CTC ER/PR protein expression needs further evaluation in larger trials.

Sieuwerts AM, Mostert B, Bolt-de Vries J, Peeters D, de Jongh FE, Stouthard JML. mRNA and microRNA expression profiles in circulating tumor cells and primary tumors of metastatic breast cancer patients. Clin Cancer Res. 2011;17(11):3600–18. doi:10.1158/1078-0432.ccr-11-0255.PubMedCrossRef

Cleator SJ, Ahamed E, Coombes RC, Palmieri C. A 2009 update on the treatment of patients with hormone receptor-positive breast cancer. Clin Breast Cancer. 2009;9(Suppl 1):S6–17. doi:10.3816/CBC.2009.s.001 G44434VK149RM452.PubMedCrossRef

Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, et al. American society of clinical oncology/college of American pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version). Arch Pathol Lab Med. 2010;134(7):e48–72. doi:10.1043/1543-2165-134.7.e48.PubMed

Lower EE, Glass EL, Bradley DA, Blau R, Heffelfinger S. Impact of metastatic estrogen receptor and progesterone receptor status on survival. Breast Cancer Res Treat. 2005;90(1):65–70. doi:10.1007/s10549-004-2756-z.PubMedCrossRef

Liedtke C, Broglio K, Moulder S, Hsu L, Kau SW, Symmans WF, et al. Prognostic impact of discordance between triple-receptor measurements in primary and recurrent breast cancer. Ann Oncol. 2009;20(12):1953–8. doi:10.1093/annonc/mdp263 mdp263.PubMedCentralPubMedCrossRef

Aitken SJ, Thomas JS, Langdon SP, Harrison DJ, Faratian D. Quantitative analysis of changes in ER, PR and HER2 expression in primary breast cancer and paired nodal metastases. Ann Oncol. 2010;21(6):1254–61. doi:10.1093/annonc/mdp427 mdp427.PubMedCrossRef

Simmons C, Miller N, Geddie W, Gianfelice D, Oldfield M, Dranitsaris G, et al. Does confirmatory tumor biopsy alter the management of breast cancer patients with distant metastases? Ann Oncol. 2009;20(9):1499–504. doi:10.1093/annonc/mdp028 mdp028.PubMedCentralPubMedCrossRef

Amir E, Miller N, Geddie W, Freedman O, Kassam F, Simmons C, et al. Prospective study evaluating the impact of tissue confirmation of metastatic disease in patients with breast cancer. J Clin Oncol. 2012;30(6):587–92. doi:10.1200/jco.2010.33.5232.PubMedCrossRef

Fehm T, Muller V, Aktas B, Janni W, Schneeweiss A, Stickeler E, et al. HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial. Breast Cancer Res Treat. 2010;124(2):403–12. doi:10.1007/s10549-010-1163-x.PubMedCrossRef

10.

Liu MC, Shields PG, Warren RD, Cohen P, Wilkinson M, Ottaviano YL, et al. Circulating tumor cells: a useful predictor of treatment efficacy in metastatic breast cancer. J Clin Oncol. 2009;27(31):5153–9. doi:10.1200/jco.2008.20.6664.PubMedCrossRef

11.

Hayes DF, Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Miller MC, et al. Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res. 2006;12(14 Pt 1):4218–24. doi:10.1158/1078-0432.CCR-05-2821 12/14/4218.PubMedCrossRef

12.

Aktas B, Muller V, Tewes M, Zeitz J, Kasimir-Bauer S, Loehberg CR, et al. Comparison of estrogen and progesterone receptor status of circulating tumor cells and the primary tumor in metastatic breast cancer patients. Gynecol Oncol. 2011;122(2):356–60. doi:10.1016/j.ygyno.2011.04.039 S0090-8258(11)00340-4.PubMedCrossRef

13.

Somlo G, Lau SK, Frankel P, Hsieh HB, Liu X, Yang L, et al. Multiple biomarker expression on circulating tumor cells in comparison to tumor tissues from primary and metastatic sites in patients with locally advanced/inflammatory, and stage IV breast cancer, using a novel detection technology. Breast Cancer Res Treat. 2011;128(1):155–63. doi:10.1007/s10549-011-1508-0.PubMedCentralPubMedCrossRef

14.

Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature. 2007;450(7173):1235–9. doi:10.1038/nature06385 nature06385.PubMedCentralPubMedCrossRef

15.

Paterlini-Brechot P, Benali NL. Circulating tumor cells (CTC) detection: clinical impact and future directions. Cancer Lett. 2007;253(2):180–204. doi:10.1016/j.canlet.2006.12.014 S0304-3835(06)00686-0.PubMedCrossRef

16.

Mayer JA, Pham T, Wong KL, Scoggin J, Sales EV, Clarin T, et al. FISH-based determination of HER2 status in circulating tumor cells isolated with the microfluidic CEE platform. Cancer Genet. 2011;204(11):589–95. doi:10.1016/j.cancergen.2011.10.011 S2210-7762(11)00304-8.PubMedCrossRef

17.

Dickson MN, Tsinberg P, Tang Z, Bischoff FZ, Wilson T, Leonard EF. Efficient capture of circulating tumor cells with a novel immunocytochemical microfluidic device. Biomicrofluidics. 2011;5:034119.CrossRef

18.

Pecot CV, Bischoff FZ, Mayer JA, Wong KL, Pham T, Bottsford-Miller J, et al. A novel platform for detection of CK+ and CK − CTCs. Cancer Discov. 2011;1(7):580–6. doi:10.1158/2159-8290.CD-11-0215 2159-8290.CD-11-0215.PubMedCentralPubMedCrossRef

19.

Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33(1):159–74.PubMedCrossRef

20.

Hollestelle A, Nagel JH, Smid M, Lam S, Elstrodt F, Wasielewski M, et al. Distinct gene mutation profiles among luminal-type and basal-type breast cancer cell lines. Breast Cancer Res Treat. 2010;121(1):53–64. doi:10.1007/s10549-009-0460-8.PubMedCrossRef

21.

Fehm T, Hoffmann O, Aktas B, Becker S, Solomayer EF, Wallwiener D, et al. Detection and characterization of circulating tumor cells in blood of primary breast cancer patients by RT-PCR and comparison to status of bone marrow disseminated cells. Breast Cancer Res. 2009;11(4):R59. doi:10.1186/bcr2349 bcr2349.PubMedCentralPubMedCrossRef

22.

Nadal R, Fernandez A, Sanchez-Rovira P, Salido M, Rodriguez M, Garcia-Puche JL, et al. Biomarkers characterization of circulating tumour cells in breast cancer patients. Breast Cancer Res. 2012;14(3):R71. doi:10.1186/bcr3180 bcr3180.PubMedCentralPubMedCrossRef

23.

Babayan A, Hannemann J, Spötter J, Müller V, Pantel K, Joosse SA. Heterogeneity of estrogen receptor expression in circulating tumor cells from metastatic breast cancer patients. PLoS One. 2013;8(9):e75038. doi:10.1371/journal.pone.0075038.PubMedCentralPubMedCrossRef

Title: Correlation of hormone receptor status between circulating tumor cells, primary tumor, and metastasis in breast cancer patients
Authors: K. Kalinsky
J. A. Mayer
X. Xu
T. Pham
K. L. Wong
E. Villarin
T. J. Pircher
M. Brown
M. A. Maurer
F. Z. Bischoff
Publication date: 01-07-2015
Publisher: Springer Milan
Published in: Clinical and Translational Oncology / Issue 7/2015
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI: https://doi.org/10.1007/s12094-015-1275-1

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods/patients

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 7/2015

GAL3ST2 from mammary gland epithelial cells affects differentiation of 3T3-L1 preadipocytes

Association of PSMA4 polymorphisms with lung cancer susceptibility and response to cisplatin-based chemotherapy in a Chinese Han population

Results of induction chemotherapy in children older than 18 months with stage-4 neuroblastoma treated with an adaptive-to-response modified N7 protocol (mN7)

Disease progression pattern in metastatic breast cancer patients treated with anti-HER2 therapies

Two novel frameshift mutations in BRCA2 gene detected by next generation sequencing in a survey of Spanish patients of breast cancer

Expression of IMP3 and IGF2 in giant cell tumor of spine is associated with tumor recurrence and angiogenesis

Keynote webinar | Spotlight on antibody–drug conjugates in cancer