Prognostic value of HER2 status on circulating tumor cells in advanced-stage breast cancer patients with HER2-negative tumors

Chun Wang; Zhaomei Mu; Zhong Ye; Zhenchao Zhang; Maysa M. Abu-Khalaf; Daniel P. Silver; Juan P. Palazzo; Geetha Jagannathan; Frederick M. Fellin; Saveri Bhattacharya; Rebecca J. Jaslow; Theodore N. Tsangaris; Adam Berger; Manish Neupane; Terrence P. Cescon; Ana Maria Lopez; Kaelan Yao; Weelic Chong; Brian Lu; Ronald E. Myers; Lifang Hou; Qiang Wei; Bingshan Li; Massimo Cristofanilli; Hushan Yang

doi:10.1007/s10549-020-05662-x

Prognostic value of HER2 status on circulating tumor cells in advanced-stage breast cancer patients with HER2-negative tumors

Chun Wang, Zhaomei Mu, Zhong Ye, Zhenchao Zhang, Maysa M. Abu-Khalaf, Daniel P. Silver, Juan P. Palazzo, Geetha Jagannathan, Frederick M. Fellin, Saveri Bhattacharya, Rebecca J. Jaslow, Theodore N. Tsangaris, Adam Berger, Manish Neupane, Terrence P. Cescon, Ana Maria Lopez, Kaelan Yao, Weelic Chong, Brian Lu, Ronald E. MyersLifang Hou, Qiang Wei, Bingshan Li, Massimo Cristofanilli, Hushan Yang^*

^*Corresponding author for this work

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

32 Scopus citations

Abstract

Purpose: Discordance between HER2 expression in tumor tissue (tHER2) and HER2 status on circulating tumor cells (cHER2) has been reported. It remains largely underexplored whether patients with tHER2⁻/cHER2⁺ can benefit from anti-HER2 targeted therapies. Methods: cHER2 status was determined in 105 advanced-stage patients with tHER2⁻ breast tumors. Association between cHER2 status and progression-free survival (PFS) was analyzed by univariate and multivariate Cox models and survival differences were compared by Kaplan–Meier method. Results: Compared to the patients with low-risk cHER2 (cHER2⁺ < 2), those with high-risk cHER2 (cHER2⁺ ≥ 2) had shorter survival time and an increased risk for disease progression (hazard ratio [HR] 2.16, 95% confidence interval [CI] 1.20–3.88, P = 0.010). Among the patients with high-risk cHER2, those who received anti-HER2 targeted therapies had improved PFS compared with those who did not (HR 0.30, 95% CI 0.10–0.92, P = 0.035). In comparison, anti-HER2 targeted therapy did not affect PFS among those with low-risk cHER2 (HR 0.70, 95% CI 0.36–1.38, P = 0.306). Similar results were obtained after adjusting covariates. A longitudinal analysis of 67 patients with cHER2 detected during follow-ups found that those whose cHER2 status changed from high-risk at baseline to low-risk at first follow-up exhibited a significantly improved survival compared to those whose cHER2 remained high-risk (median PFS: 11.7 weeks vs. 2.0 weeks, log-rank P = 0.001). Conclusion: In advanced-stage breast cancer patients with tHER2⁻ tumors, cHER2 status has the potential to guide the use of anti-HER2 targeted therapy in patients with high-risk cHER2.

Original language	English (US)
Pages (from-to)	679-689
Number of pages	11
Journal	Breast Cancer Research and Treatment
Volume	181
Issue number	3
DOIs	https://doi.org/10.1007/s10549-020-05662-x
State	Published - Jun 1 2020

Funding

This study was funded by National Cancer Institute Grant (R01CA207468), Pennsylvania Department of Health Grant (SAP# 4100062221), The Inflammatory Breast Cancer Network Foundation, The Jamie Lieberman Memorial Endowment Fund. Research reported in this publication utilized the Circulating Tumor Cell Core Facility at the Sidney Kimmel Cancer Center at Jefferson Health and was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA056036. The funding agencies were not involved in the design, conduct, analysis or interpretation of the study.

Keywords

Breast cancer
Circulating tumor cell (CTC)
Human epidermal growth factor receptor 2 (HER2)
Progression-free survival (PFS)

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s10549-020-05662-x

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Wang, C., Mu, Z., Ye, Z., Zhang, Z., Abu-Khalaf, M. M., Silver, D. P., Palazzo, J. P., Jagannathan, G., Fellin, F. M., Bhattacharya, S., Jaslow, R. J., Tsangaris, T. N., Berger, A., Neupane, M., Cescon, T. P., Lopez, A. M., Yao, K., Chong, W., Lu, B., ... Yang, H. (2020). Prognostic value of HER2 status on circulating tumor cells in advanced-stage breast cancer patients with HER2-negative tumors. Breast Cancer Research and Treatment, 181(3), 679-689. https://doi.org/10.1007/s10549-020-05662-x

@article{26dfb73543304cf29da2491a00ce4413,

title = "Prognostic value of HER2 status on circulating tumor cells in advanced-stage breast cancer patients with HER2-negative tumors",

abstract = "Purpose: Discordance between HER2 expression in tumor tissue (tHER2) and HER2 status on circulating tumor cells (cHER2) has been reported. It remains largely underexplored whether patients with tHER2−/cHER2+ can benefit from anti-HER2 targeted therapies. Methods: cHER2 status was determined in 105 advanced-stage patients with tHER2− breast tumors. Association between cHER2 status and progression-free survival (PFS) was analyzed by univariate and multivariate Cox models and survival differences were compared by Kaplan–Meier method. Results: Compared to the patients with low-risk cHER2 (cHER2+ < 2), those with high-risk cHER2 (cHER2+ ≥ 2) had shorter survival time and an increased risk for disease progression (hazard ratio [HR] 2.16, 95% confidence interval [CI] 1.20–3.88, P = 0.010). Among the patients with high-risk cHER2, those who received anti-HER2 targeted therapies had improved PFS compared with those who did not (HR 0.30, 95% CI 0.10–0.92, P = 0.035). In comparison, anti-HER2 targeted therapy did not affect PFS among those with low-risk cHER2 (HR 0.70, 95% CI 0.36–1.38, P = 0.306). Similar results were obtained after adjusting covariates. A longitudinal analysis of 67 patients with cHER2 detected during follow-ups found that those whose cHER2 status changed from high-risk at baseline to low-risk at first follow-up exhibited a significantly improved survival compared to those whose cHER2 remained high-risk (median PFS: 11.7 weeks vs. 2.0 weeks, log-rank P = 0.001). Conclusion: In advanced-stage breast cancer patients with tHER2− tumors, cHER2 status has the potential to guide the use of anti-HER2 targeted therapy in patients with high-risk cHER2.",

keywords = "Breast cancer, Circulating tumor cell (CTC), Human epidermal growth factor receptor 2 (HER2), Progression-free survival (PFS)",

author = "Chun Wang and Zhaomei Mu and Zhong Ye and Zhenchao Zhang and Abu-Khalaf, {Maysa M.} and Silver, {Daniel P.} and Palazzo, {Juan P.} and Geetha Jagannathan and Fellin, {Frederick M.} and Saveri Bhattacharya and Jaslow, {Rebecca J.} and Tsangaris, {Theodore N.} and Adam Berger and Manish Neupane and Cescon, {Terrence P.} and Lopez, {Ana Maria} and Kaelan Yao and Weelic Chong and Brian Lu and Myers, {Ronald E.} and Lifang Hou and Qiang Wei and Bingshan Li and Massimo Cristofanilli and Hushan Yang",

note = "Funding Information: This study was funded by National Cancer Institute Grant (R01CA207468), Pennsylvania Department of Health Grant (SAP# 4100062221), The Inflammatory Breast Cancer Network Foundation, The Jamie Lieberman Memorial Endowment Fund. Research reported in this publication utilized the Circulating Tumor Cell Core Facility at the Sidney Kimmel Cancer Center at Jefferson Health and was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA056036. The funding agencies were not involved in the design, conduct, analysis or interpretation of the study. Publisher Copyright: {\textcopyright} 2020, Springer Science+Business Media, LLC, part of Springer Nature.",

year = "2020",

month = jun,

day = "1",

doi = "10.1007/s10549-020-05662-x",

language = "English (US)",

volume = "181",

pages = "679--689",

journal = "Breast Cancer Research and Treatment",

issn = "0167-6806",

publisher = "Springer New York",

number = "3",

}

Wang, C, Mu, Z, Ye, Z, Zhang, Z, Abu-Khalaf, MM, Silver, DP, Palazzo, JP, Jagannathan, G, Fellin, FM, Bhattacharya, S, Jaslow, RJ, Tsangaris, TN, Berger, A, Neupane, M, Cescon, TP, Lopez, AM, Yao, K, Chong, W, Lu, B, Myers, RE, Hou, L, Wei, Q, Li, B, Cristofanilli, M & Yang, H 2020, 'Prognostic value of HER2 status on circulating tumor cells in advanced-stage breast cancer patients with HER2-negative tumors', Breast Cancer Research and Treatment, vol. 181, no. 3, pp. 679-689. https://doi.org/10.1007/s10549-020-05662-x

TY - JOUR

T1 - Prognostic value of HER2 status on circulating tumor cells in advanced-stage breast cancer patients with HER2-negative tumors

AU - Wang, Chun

AU - Mu, Zhaomei

AU - Ye, Zhong

AU - Zhang, Zhenchao

AU - Abu-Khalaf, Maysa M.

AU - Silver, Daniel P.

AU - Palazzo, Juan P.

AU - Jagannathan, Geetha

AU - Fellin, Frederick M.

AU - Bhattacharya, Saveri

AU - Jaslow, Rebecca J.

AU - Tsangaris, Theodore N.

AU - Berger, Adam

AU - Neupane, Manish

AU - Cescon, Terrence P.

AU - Lopez, Ana Maria

AU - Yao, Kaelan

AU - Chong, Weelic

AU - Lu, Brian

AU - Myers, Ronald E.

AU - Hou, Lifang

AU - Wei, Qiang

AU - Li, Bingshan

AU - Cristofanilli, Massimo

AU - Yang, Hushan

N1 - Funding Information: This study was funded by National Cancer Institute Grant (R01CA207468), Pennsylvania Department of Health Grant (SAP# 4100062221), The Inflammatory Breast Cancer Network Foundation, The Jamie Lieberman Memorial Endowment Fund. Research reported in this publication utilized the Circulating Tumor Cell Core Facility at the Sidney Kimmel Cancer Center at Jefferson Health and was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA056036. The funding agencies were not involved in the design, conduct, analysis or interpretation of the study. Publisher Copyright: © 2020, Springer Science+Business Media, LLC, part of Springer Nature.

PY - 2020/6/1

Y1 - 2020/6/1

N2 - Purpose: Discordance between HER2 expression in tumor tissue (tHER2) and HER2 status on circulating tumor cells (cHER2) has been reported. It remains largely underexplored whether patients with tHER2−/cHER2+ can benefit from anti-HER2 targeted therapies. Methods: cHER2 status was determined in 105 advanced-stage patients with tHER2− breast tumors. Association between cHER2 status and progression-free survival (PFS) was analyzed by univariate and multivariate Cox models and survival differences were compared by Kaplan–Meier method. Results: Compared to the patients with low-risk cHER2 (cHER2+ < 2), those with high-risk cHER2 (cHER2+ ≥ 2) had shorter survival time and an increased risk for disease progression (hazard ratio [HR] 2.16, 95% confidence interval [CI] 1.20–3.88, P = 0.010). Among the patients with high-risk cHER2, those who received anti-HER2 targeted therapies had improved PFS compared with those who did not (HR 0.30, 95% CI 0.10–0.92, P = 0.035). In comparison, anti-HER2 targeted therapy did not affect PFS among those with low-risk cHER2 (HR 0.70, 95% CI 0.36–1.38, P = 0.306). Similar results were obtained after adjusting covariates. A longitudinal analysis of 67 patients with cHER2 detected during follow-ups found that those whose cHER2 status changed from high-risk at baseline to low-risk at first follow-up exhibited a significantly improved survival compared to those whose cHER2 remained high-risk (median PFS: 11.7 weeks vs. 2.0 weeks, log-rank P = 0.001). Conclusion: In advanced-stage breast cancer patients with tHER2− tumors, cHER2 status has the potential to guide the use of anti-HER2 targeted therapy in patients with high-risk cHER2.

AB - Purpose: Discordance between HER2 expression in tumor tissue (tHER2) and HER2 status on circulating tumor cells (cHER2) has been reported. It remains largely underexplored whether patients with tHER2−/cHER2+ can benefit from anti-HER2 targeted therapies. Methods: cHER2 status was determined in 105 advanced-stage patients with tHER2− breast tumors. Association between cHER2 status and progression-free survival (PFS) was analyzed by univariate and multivariate Cox models and survival differences were compared by Kaplan–Meier method. Results: Compared to the patients with low-risk cHER2 (cHER2+ < 2), those with high-risk cHER2 (cHER2+ ≥ 2) had shorter survival time and an increased risk for disease progression (hazard ratio [HR] 2.16, 95% confidence interval [CI] 1.20–3.88, P = 0.010). Among the patients with high-risk cHER2, those who received anti-HER2 targeted therapies had improved PFS compared with those who did not (HR 0.30, 95% CI 0.10–0.92, P = 0.035). In comparison, anti-HER2 targeted therapy did not affect PFS among those with low-risk cHER2 (HR 0.70, 95% CI 0.36–1.38, P = 0.306). Similar results were obtained after adjusting covariates. A longitudinal analysis of 67 patients with cHER2 detected during follow-ups found that those whose cHER2 status changed from high-risk at baseline to low-risk at first follow-up exhibited a significantly improved survival compared to those whose cHER2 remained high-risk (median PFS: 11.7 weeks vs. 2.0 weeks, log-rank P = 0.001). Conclusion: In advanced-stage breast cancer patients with tHER2− tumors, cHER2 status has the potential to guide the use of anti-HER2 targeted therapy in patients with high-risk cHER2.

KW - Breast cancer

KW - Circulating tumor cell (CTC)

KW - Human epidermal growth factor receptor 2 (HER2)

KW - Progression-free survival (PFS)

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Prognostic value of HER2 status on circulating tumor cells in advanced-stage breast cancer patients with HER2-negative tumors

Abstract

Funding

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UN SDGs

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