Gabe S Sonke1, Sabine C Linn2,3,4, Gwen M H E Dackus5,6, Katarzyna Jóźwiak7,8, Elsken van der Wall9, Paul J van Diest6, Michael Hauptmann7,8, Sabine Siesling10,11. 1. Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. 2. Division of Molecular Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. s.linn@nki.nl. 3. Department of Pathology, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands. s.linn@nki.nl. 4. Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. s.linn@nki.nl. 5. Division of Molecular Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands. 6. Department of Pathology, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands. 7. Department of Epidemiology and Biostatistics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands. 8. Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Haus O, Fehrbelliner Straße 38, 16816, Neuruppin, Germany. 9. Division of Internal Medicine and Dermatology, University Medical Center Utrecht, Hpn Q05.4300, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. 10. Department of Research and Development, Netherlands Comprehensive Cancer Organisation The Netherlands, PO Box 19079, 3501 DB, Utrecht, The Netherlands. 11. Department of Health Technology & Services Research, Technical Medical Center, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands.
Abstract
PURPOSE: The addition of trastuzumab to adjuvant chemotherapy has improved the outcome of human epidermal growth-factor receptor 2 (HER2)-positive breast cancer. Uncertainty remains about the optimal timing of trastuzumab treatment. Therefore, we compared long-term outcome after concurrent versus sequential treatment, in a population-based setting, using data from the nationwide Netherlands Cancer Registry. METHODS: We identified 1843 women diagnosed in The Netherlands from January 1st 2005 until January 1st 2008 with primary, HER2-positive, T1-4NanyM0 breast cancer who received adjuvant chemotherapy and trastuzumab. Kaplan-Meier survival estimates and Cox regression were used to compare recurrence-free survival (RFS) and overall survival (OS) between women who received trastuzumab concurrently with versus sequentially after chemotherapy. Hazard ratios (HR) were adjusted for age, year of diagnosis, grade, pathological T-stage, number of positive lymph nodes, ER-status, PR-status, socio-economic status, radiotherapy, hormonal therapy, ovarian ablation, and type of chemotherapy. RESULTS: After a median follow-up of 8.2 years, RFS events had occurred in 224 out of 1235 (18.1%) concurrently treated women and 129 out of 608 (21.2%) sequentially treated women (adjusted-HR 0.91; 95% confidence interval (CI) 0.67-1.24; P = 0.580). Deaths occurred in 182/1235 (14.7%) concurrently treated women and 104/608 (17.1%) sequentially treated women (adjusted-HR 0.92; 95% CI 0.65-1.29; P = 0.635). CONCLUSIONS: The results of this population-based study are consistent with earlier randomized trials, demonstrating a non-significant difference in outcome for concurrently treated women compared to those who were treated sequentially, suggesting both options are justified.
PURPOSE: The addition of trastuzumab to adjuvant chemotherapy has improved the outcome of human epidermal growth-factor receptor 2 (HER2)-positive breast cancer. Uncertainty remains about the optimal timing of trastuzumab treatment. Therefore, we compared long-term outcome after concurrent versus sequential treatment, in a population-based setting, using data from the nationwide Netherlands Cancer Registry. METHODS: We identified 1843 women diagnosed in The Netherlands from January 1st 2005 until January 1st 2008 with primary, HER2-positive, T1-4NanyM0 breast cancer who received adjuvant chemotherapy and trastuzumab. Kaplan-Meier survival estimates and Cox regression were used to compare recurrence-free survival (RFS) and overall survival (OS) between women who received trastuzumab concurrently with versus sequentially after chemotherapy. Hazard ratios (HR) were adjusted for age, year of diagnosis, grade, pathological T-stage, number of positive lymph nodes, ER-status, PR-status, socio-economic status, radiotherapy, hormonal therapy, ovarian ablation, and type of chemotherapy. RESULTS: After a median follow-up of 8.2 years, RFS events had occurred in 224 out of 1235 (18.1%) concurrently treated women and 129 out of 608 (21.2%) sequentially treated women (adjusted-HR 0.91; 95% confidence interval (CI) 0.67-1.24; P = 0.580). Deaths occurred in 182/1235 (14.7%) concurrently treated women and 104/608 (17.1%) sequentially treated women (adjusted-HR 0.92; 95% CI 0.65-1.29; P = 0.635). CONCLUSIONS: The results of this population-based study are consistent with earlier randomized trials, demonstrating a non-significant difference in outcome for concurrently treated women compared to those who were treated sequentially, suggesting both options are justified.
Entities:
Keywords:
Adjuvant treatment; Breast cancer; Concurrent; Human epidermal growth-factor receptor 2; Sequential; Trastuzumab
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