Abstract P5-21-03: Delay in trastuzumab initiation leads to decreased overall survival in patients with HER2+ early stage breast cancer
Authors: Gallagher Christopher M , More Kenneth , Masaquel Anthony , Kamath Tripthi , Guerin Annie , Ionescu-Ittu Raluca , Gauthier-Loiselle Marjolaine , Nitulescu Roy , Sicignano Nicholas , Barnett Brian , Wu Eric 
Published: May 2015

Abstract
Background
Trastuzumab reduces the risk of relapse in women with HER2+ early stage breast cancer. Yet, little information exists on the timing of trastuzumab initiation and its association with relapse and survival outcomes in these patients. The study aimed to investigate the impact of delaying the initiation of adjuvant trastuzumab treatment for &gt;6 months on time to relapse, overall survival, and relapse-free survival among patients with HER2+ early stage breast cancer who did not receive neoadjuvant therapy.
Methods
Adult women initiating trastuzumab adjuvant therapy within 1 year of breast cancer surgery who did not receive neoadjuvant therapy were selected from the US Department of Defense health claims database from 01/2003 to 12/2012 (N = 2,749). By design, participants had to be alive and relapse-free at the time they initiated adjuvant trastuzumab. Patients were classified into two groups based on the time from breast cancer diagnosis to trastuzumab initiation: ≤6 months and &gt;6 months. An algorithm based on secondary neoplasm ICD9 codes along with treatment gaps and initiations was used to identify relapses. Percent relapses and/or deaths were reported by study groups and compared using χ2 tests. The impact of delaying trastuzumab initiation on time to relapse, overall survival, and relapse-free survival was estimated from Cox regression models adjusted for age, overall comorbidity profile at the time of the BC diagnosis (Charlson index), type of surgery (breast conserving vs. breast removing), and radiotherapy (prior to the initiation of trastuzumab). In all three Cox models the follow-up started at adjuvant trastuzumab initiation.
Results
Of 2,749 women who met the selection criteria, 79.3% initiated adjuvant trastuzumab ≤6 months of diagnosis and 20.7% initiated adjuvant trastuzumab &gt;6 months after the diagnosis (Table). Patients who delayed the initiation of trastuzumab for &gt;6 months were younger (57.2% aged &lt;65 years vs. 50.9%, p = .008) and a higher proportion of them received radiotherapy prior to the initiation of trastuzumab compared to those who initiated trastuzumab earlier (77.2% vs. 53.1%, p &lt; .001). There were no significant differences between the two groups in overall comorbidity profile and type of surgery. Patients who initiated trastuzumab &gt;6 months after diagnosis had a higher risk of relapse, death, or relapse/death than those who initiated trastuzumab ≤6 months of diagnosis in both unadjusted and adjusted analyses (Table).
N events (% events)Hazard Ratio (95% CI) ≤6 months group N = 2,180&gt;6 months group N = 569p-value&gt;6 months group vs ≤6 months groupRelapse outcome333 (15.2%)134 (24.3%)&lt; .0011.40 (1.14 - 1.72)*Death outcome (overall survival)138 (6.3%)64 (11.6%)&lt; .0011.44 (1.06 - 1.96)*Relapse or death outcome (Relapse-free survival)386 (17.6%)148 (26.8%)&lt; .0011.33 (1.09 - 1.61)**p-value &lt; .05
Conclusions
The results of this population-based study among patients with HER2+ early stage breast cancer who did not receive neoadjuvant therapy suggest that delays of over 6 months in the initiation of trastuzumab among HER2+ early stage breast cancer patients are associated with a higher risk of relapse and shorter overall survival and relapse-free survival.
Disclaimer
Research derived from an IRB approved protocol at Naval Medical Center Portsmouth, VA. The views expressed in this abstract are those of the authors and do not necessarily reflect the official policy or position of the Department of the Army, Department of the Navy, Department of Defense or the United States Government. Dr. C.G. and Dr. K.M. are members of the U.S. military. This work was prepared as part of their official duties. Title 17 U.S.C. 105 provides that 'Copyright protection under this title is not available for any work of the United States Government.' Title 17 U.S.C. 101 defines a United States Government work as a work prepared by a military service member or employee of the United States Government as part of that person's official duties.
Citation Format: Christopher M Gallagher, Kenneth More, Anthony Masaquel, Tripthi Kamath, Annie Guerin, Raluca Ionescu-Ittu, Marjolaine Gauthier-Loiselle, Roy Nitulescu, Nicholas Sicignano, Brian Barnett, Eric Wu. Delay in trastuzumab initiation leads to decreased overall survival in patients with HER2+ early stage breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-21-03.