The HER2 phenotype of circulating tumor cells in HER2-positive early breast cancer
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The HER2 phenotype of circulating tumor cells in HER2-positive early breast cancer : A translational research project of a prospective randomized phase III trial. / Jaeger, B A S; Neugebauer, J; Andergassen, U; Melcher, C; Schochter, F; Mouarrawy, D; Ziemendorff, G; Clemens, M; V Abel, E; Heinrich, G; Schueller, K; Schneeweiss, A; Fasching, P; Beckmann, M W; Scholz, Ch; Friedl, T W P; Friese, K; Pantel, K; Fehm, T; Janni, W; Rack, B.
In: PLOS ONE, Vol. 12, No. 6, 2017, p. e0173593.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The HER2 phenotype of circulating tumor cells in HER2-positive early breast cancer
T2 - A translational research project of a prospective randomized phase III trial
AU - Jaeger, B A S
AU - Neugebauer, J
AU - Andergassen, U
AU - Melcher, C
AU - Schochter, F
AU - Mouarrawy, D
AU - Ziemendorff, G
AU - Clemens, M
AU - V Abel, E
AU - Heinrich, G
AU - Schueller, K
AU - Schneeweiss, A
AU - Fasching, P
AU - Beckmann, M W
AU - Scholz, Ch
AU - Friedl, T W P
AU - Friese, K
AU - Pantel, K
AU - Fehm, T
AU - Janni, W
AU - Rack, B
PY - 2017
Y1 - 2017
N2 - BACKGROUND: HER2 is one of the predominant therapeutic targets in breast cancer. The metastatic selection process may lead to discrepancies between the HER2 status of the primary tumor and circulating tumor cells (CTCs). This study analyzed the HER2 status of CTCs in patients with HER2-positive primary breast cancer at the time of diagnosis. Aim of the study was to assess potential discordance of HER2 status between primary tumor and CTCs, as this may have important implications for the use of HER2-targeted therapy.METHODS: The number and HER2 status of CTCs out of 30ml peripheral blood were assessed in 642 patients using the CellSearch System (Janssen Diagnostics, USA). The cutoff for CTC positivity was the presence of at least 1 CTC, and the cutoff for HER2 positivity of CTCs was the presence of at least 1 CTC with a strong HER2 staining.RESULTS: 258 (40.2%) of the 642 patients were positive for CTCs (median 2; range 1-1,689). 149 (57.8%) of these 258 patients had at least 1 CTC with strong HER2 staining. The presence of HER2-positive CTCs was not associated with tumor size (p = 0.335), histopathological grading (p = 0.976), hormone receptor status (ER: p = 0.626, PR: p = 0.263) or axillary lymph node involvement (p = 0.430). Overall, 83 (32.2%) of the CTC-positive patients exclusively had CTCs with strong HER2 staining, whereas 31 (12.0%) had only CTCs with negative HER2 staining. Within-sample variation in the HER2 status of CTCs was found in 86 (57.8%) of the 149 patients with more than 1 CTC.CONCLUSION: This study demonstrated that discordance between the HER2 expression of CTCs and that of the primary tumor frequently occurs in early breast cancer. Future follow-up evaluation will assess whether this discrepancy may contribute to trastuzumab resistance.
AB - BACKGROUND: HER2 is one of the predominant therapeutic targets in breast cancer. The metastatic selection process may lead to discrepancies between the HER2 status of the primary tumor and circulating tumor cells (CTCs). This study analyzed the HER2 status of CTCs in patients with HER2-positive primary breast cancer at the time of diagnosis. Aim of the study was to assess potential discordance of HER2 status between primary tumor and CTCs, as this may have important implications for the use of HER2-targeted therapy.METHODS: The number and HER2 status of CTCs out of 30ml peripheral blood were assessed in 642 patients using the CellSearch System (Janssen Diagnostics, USA). The cutoff for CTC positivity was the presence of at least 1 CTC, and the cutoff for HER2 positivity of CTCs was the presence of at least 1 CTC with a strong HER2 staining.RESULTS: 258 (40.2%) of the 642 patients were positive for CTCs (median 2; range 1-1,689). 149 (57.8%) of these 258 patients had at least 1 CTC with strong HER2 staining. The presence of HER2-positive CTCs was not associated with tumor size (p = 0.335), histopathological grading (p = 0.976), hormone receptor status (ER: p = 0.626, PR: p = 0.263) or axillary lymph node involvement (p = 0.430). Overall, 83 (32.2%) of the CTC-positive patients exclusively had CTCs with strong HER2 staining, whereas 31 (12.0%) had only CTCs with negative HER2 staining. Within-sample variation in the HER2 status of CTCs was found in 86 (57.8%) of the 149 patients with more than 1 CTC.CONCLUSION: This study demonstrated that discordance between the HER2 expression of CTCs and that of the primary tumor frequently occurs in early breast cancer. Future follow-up evaluation will assess whether this discrepancy may contribute to trastuzumab resistance.
KW - Adult
KW - Aged
KW - Biomarkers, Tumor
KW - Breast Neoplasms
KW - Female
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Middle Aged
KW - Neoplasm Staging
KW - Neoplastic Cells, Circulating
KW - Receptor, ErbB-2
KW - Translational Medical Research
KW - Trastuzumab
KW - Clinical Trial, Phase III
KW - Journal Article
KW - Randomized Controlled Trial
U2 - 10.1371/journal.pone.0173593
DO - 10.1371/journal.pone.0173593
M3 - SCORING: Journal article
C2 - 28586395
VL - 12
SP - e0173593
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 6
ER -