Prognostic value of baseline serum HER2 extracellular domain level with a cut-off value of 15 ng/mL in patients with breast cancer: a systematic review and meta-analysis

Zhang, Zhuo; Li, Chao; Fan, Hongwei; Xiang, Qian; Xu, Ling; Liu, Qianxin; Zhou, Shuang; Xie, Qiufen; Chen, Shuqing; Mu, Guangyan; Chen, Yimin

doi:10.1007/s10549-018-4942-4

Cited by 19 publications

(16 citation statements)

References 32 publications

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“…Another recent meta-analysis based on 15 prospective and 8 retrospective studies, investigating the prognostic value of HER2 ECD with the FDA approved threshold of 15 ng/ml, concluded that higher levels are correlated with poorer OS with a hazard ratio (HR) of 2.3 (CI:2.0-2.6) [23]. Our results are very much in line with this meta-analysis despite our threshold, with respect to OS for patients treated with upfront TChemo, had to be set at a higher level (35 ng/ml).…”

Section: Discussionmentioning

confidence: 99%

Plasma HER2ECD a promising test for patient prognosis and prediction of response in HER2 positive breast cancer: results of a randomized study - SAKK 22/99

et al. 2020

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Background: The HER2 extracellular domain shed in blood (HER2 ECD) is reported to rise and fall in parallel with HER2+ breast cancer behavior. In this study, we evaluated the clinical relevance of plasma HER2 ECD values in patients with metastatic breast cancer treated in the SAKK22/99 trial comparing trastuzumab monotherapy followed by trastuzumab-chemotherapy combination at progression versus upfront combination therapy. Methods: Quantitative assessment of plasma HER2 ECD was performed in 133 patients at baseline; after 2-24 h; at 3 weeks; at first response evaluation (8-9 weeks); and at tumor progression. Associations with tumor characteristics, disease course and trial treatment were evaluated. Results: Baseline HER2 ECD levels were stable within 24 h after the first trastuzumab injection. These plasma values correlated positively with the HER2 gene ratio (r s = 0.39, P < 0.001) and HER2 protein expression levels (r s = 0.36, P < 0.001) but not with ER/PR status of the primary tumor. HER2 ECD baseline levels were positively associated with the presence of visceral disease (P = 0.05) and poor patients' outcome (Cox-regression: P = 0.009). Patients with high baseline levels (> 35 ng/ml) had the worst overall survival (P = 0.03) if treated with upfront combination therapy. Conversely, patients with low HER2 ECD baseline values (< 15 ng/ml) had longer time to progression on combined trastuzumab-chemotherapy when first treated with trastuzumab monotherapy (P = 0.02). Monitoring HER2 ECD levels during the course of the trial revealed significant time (P = 0.001) and time-treatment arm interactions (P = 0.0007). Under upfront trastuzumab alone, the HER2 ECD levels remained stable until just before disease progression. In patients responding to combination treatment HER2 ECD levels decreased to > 20%. Conclusions: Plasma HER2 ECD levels in patients with metastatic breast cancer reflect HER2 disease status. This robust biomarker might help identifying patients without visceral disease profiting from a sequential treatment's modality. Monitoring HER2 ECD levels during trastuzumab monotherapy could help defining the optimal time to introduce chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Plasma HER2ECD a promising test for patient prognosis and prediction of response in HER2 positive breast cancer: results of a randomized study - SAKK 22/99

et al. 2020

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“…Another recent meta-analysis based on 15 prospective and 8 retrospective studies, investigating the prognostic value of HER2 ECD with the FDA approved threshold of 15ng/ml, concluded that higher levels are correlated with poorer OS with a hazard ratio (HR) of 2.3 (CI:2.0-2.6) [23]. Our results are very much in line with this meta-analysis despite our threshold, with respect to OS for patients treated with upfront TChemo, had to be set at a higher level (35ng/ml).…”

Section: Discussionmentioning

confidence: 99%

Plasma HER2ECD a promising test for patient prognosis and prediction of response in HER2 positive breast cancer: Results of a randomized study - SAKK 22/99.

Eppenberger‐Castori

Klingbiel

Ruhstaller

et al. 2020

Preprint

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Background: The HER2 extracellular domain shed in blood (HER2ECD) is reported to rise and fall in parallel with HER2+ breast cancer behavior. In this study, we evaluated the clinical relevance of plasma HER2ECD values in patients with metastatic breast cancer treated in the SAKK22/99 trial comparing trastuzumab monotherapy followed by trastuzumab-chemotherapy combination at progression versus upfront combination therapy. Methods : Quantitative assessment of plasma HER2ECD was performed in 133 patients at baseline; after 2-24 hours; at 3 weeks; at first response evaluation (8-9 weeks); and at tumor progression. Associations with tumor characteristics, disease course and trial treatment were evaluated.Results: Baseline HER2ECD levels were stable within 24 hours after the first trastuzumab injection. These plasma values correlated positively with the HER2 gene ratio (rs=0.39, P<0.001) and HER2 protein expression levels (rs=0.36, P<0.001) but not with ER/PR status of the primary tumor. HER2ECD baseline levels were positively associated with the presence of visceral disease (P=0.05) and poor patients’ outcome (Cox-regression: P=0.009). Patients with high baseline levels (>35ng/ml) had the worst overall survival (P=0.03) if treated with upfront combination therapy. Conversely, patients with low HER2ECD baseline values (<15ng/ml) had longer time to progression on combined trastuzumab-chemotherapy when first treated with trastuzumab monotherapy (P=0.02). Monitoring HER2ECD levels during the course of the trial revealed significant time (P=0.001) and time-treatment arm interactions (P=0.0007). Under upfront trastuzumab alone, the HER2ECD levels remained stable until just before disease progression. In patients responding to combination treatment HER2ECD levels decreased to >20%. Conclusions: Plasma HER2ECD levels in patients with metastatic breast cancer reflect HER2 disease status. This robust biomarker might help identifying patients without visceral disease profiting from a sequential treatment’s modality. Monitoring HER2ECD levels during trastuzumab monotherapy could help defining the optimal time to introduce chemotherapy.

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“…The test cut-off value recommended by the manufacturer in serum of primary and metastatic patients 5 is 15 ng/ml [19][20][21][22]. This threshold is used to discriminate HER2+ from HER2 negative patients and is known to be indicative for bad prognosis under chemotherapy alone.…”

Section: Discussionmentioning

confidence: 99%

“…Another recent meta-analysis based on 15 prospective and 8 retrospective studies, investigating the prognostic value of HER2ECD with the FDA approved threshold of 15ng/ml, concluded that higher levels are correlated with poorer OS with a hazard ratio (HR) of 2.3 (CI:2.0-2.6) [21]. Our results are very much in line with this meta-analysis despite our threshold, with respect to OS for patients treated with upfront TChemo, had to be set at a higher level (35ng/ml).…”

Section: Discussionmentioning

confidence: 99%

Plasma HER2ECD a promising test for patient prognosis and prediction of response in HER2 positive breast cancer: Results of a randomized study - SAKK 22/99

Eppenberger‐Castori

Klingbiel

Ruhstaller

et al. 2019

Preprint

View full text Add to dashboard Cite

Background The HER2 extracellular domain shed in blood (HER2ECD) is reported to rise and fall in parallel with HER2+ breast cancer behavior. In this study, we evaluated the clinical relevance of plasma HER2ECD values in patients with metastatic breast cancer treated in the SAKK22/99 trial comparing trastuzumab monotherapy followed by trastuzumab-chemotherapy combination at progression versus upfront combination therapy. Methods Quantitative assessment of plasma HER2ECD was performed in 133 patients at baseline; after 2-24 hours; at 3 weeks; at first response evaluation (8-9 weeks); and at tumor progression. Associations with tumor characteristics, disease course and trial treatment were evaluated. Results Baseline HER2ECD levels were stable within 24 hours after the first trastuzumab injection. These plasma values correlated positively with the HER2 gene ratio (rs=0.39, P<0.001) and HER2 protein expression levels (rs=0.36, P<0.001) but not with ER/PR status of the primary tumor. HER2ECD baseline levels were positively associated with the presence of visceral disease (P=0.05) and poor patients’ outcome (Cox-regression: P=0.009). Patients with high baseline levels (>35ng/ml) had the worst overall survival (P=0.03) if treated with upfront combination therapy. Conversely, patients with low HER2ECD baseline values (<15ng/ml) had longer TTP-TChemo when first treated with trastuzumab monotherapy (P=0.02). Monitoring HER2ECD levels during the course of the trial revealed significant time (P=0.001) and time-treatment arm interactions (P=0.0007). Under upfront trastuzumab alone, the HER2ECD levels remained stable until just before disease progression. In patients responding to combination treatment HER2ECD levels decreased to >20%. Conclusions Plasma HER2ECD levels in patients with metastatic breast cancer reflect HER2 disease status. This robust biomarker might help identifying patients without visceral disease profiting from a sequential treatment’s modality. Monitoring HER2ECD levels during trastuzumab monotherapy could help defining the optimal time to introduce chemotherapy.

show abstract

Prognostic value of baseline serum HER2 extracellular domain level with a cut-off value of 15 ng/mL in patients with breast cancer: a systematic review and meta-analysis

Cited by 19 publications

References 32 publications

Plasma HER2ECD a promising test for patient prognosis and prediction of response in HER2 positive breast cancer: results of a randomized study - SAKK 22/99

Plasma HER2ECD a promising test for patient prognosis and prediction of response in HER2 positive breast cancer: results of a randomized study - SAKK 22/99

Plasma HER2ECD a promising test for patient prognosis and prediction of response in HER2 positive breast cancer: Results of a randomized study - SAKK 22/99.

Plasma HER2ECD a promising test for patient prognosis and prediction of response in HER2 positive breast cancer: Results of a randomized study - SAKK 22/99

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