Chun Wang1, Zhaomei Mu2, Zhong Ye1, Zhenchao Zhang1, Maysa M Abu-Khalaf1, Daniel P Silver1, Juan P Palazzo3, Geetha Jagannathan3, Frederick M Fellin1, Saveri Bhattacharya1, Rebecca J Jaslow1, Theodore N Tsangaris1, Adam Berger4, Manish Neupane1, Terrence P Cescon5, AnaMaria Lopez1, Kaelan Yao1, Weelic Chong1, Brian Lu1, Ronald E Myers1, Lifang Hou6, Qiang Wei7, Bingshan Li7, Massimo Cristofanilli8, Hushan Yang9. 1. Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA. 2. Division of Hematology and Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA. 3. Department of Pathology, Thomas Jefferson University, Philadelphia, PA, 19107, USA. 4. Department of Surgery, Thomas Jefferson University, Philadelphia, PA, 19107, USA. 5. Department of Hematology Oncology, Reading Hospital, West Reading, PA, 19611, USA. 6. Department of Preventive Medicine, Northwestern University, Chicago, IL, 60611, USA. 7. Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37235, USA. 8. Division of Hematology and Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA. massimo.cristofanilli@nm.org. 9. Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA. hushan.yang@jefferson.edu.
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.
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 cancerpatients with tHER2- tumors, cHER2 status has the potential to guide the use of anti-HER2 targeted therapy in patients with high-risk cHER2.
Entities:
Keywords:
Breast cancer; Circulating tumor cell (CTC); Human epidermal growth factor receptor 2 (HER2); Progression-free survival (PFS)
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