Abstract P5-20-05: Impact of type of (neo)adjuvant systemic therapy (AdjTx) and total exposure to trastuzumab (TET) on long-term outcome of HER2-positive (HER2+) early stage breast cancer (ESBrCa)
Authors: G Gullo, N Walsh, D Fennelly, J Walshe, K O'Mahony, N Silva, J Ballot, G Calzaferri, C Quinn, D McDonnell, J Crown
Journal: Cancer Research (2018)

Abstract Background Trastuzumab (T) administered for 12 months (mos) as part of a taxane (Tax)– or Tax+anthracycline (Anthra)–based AdjTx is the standard of care as (neo)AdjTx of HER2+ ESBrCa. Several prospective randomized trials have investigated a shorter duration of Adj T (i.e. 9 weeks or 6 mos) compared to standard 12 mos of T. However, the results have not been conclusive so far. The impact of administering non-Tax/non-Anthra-based AdjTx and single-agent T on long-term outcome of HER2+ ESBrCa is not fully known. Methods We conducted a retrospective analysis on a prospectively maintained departmental database of all patients (pts) with Stage I-III HER2+ ESBrCa treated with at least one dose of (neo)Adj T. Pre-planned duration of T was 12 mos for all pts. TTE was defined as the interval in weeks between the first and the last dose of T. In order to ensure that most pts had a minimum FU of 3 yrs we included all pts who received 1st T before March 31st 2014. The database was locked for outcome analyses on March 31st 2017. Results 506 pts treated between October 2001 and March 2014 were included in the study. Main pts characteristics: median age: 55 years (range: 26-85), oestrogen (ER) and/or progesterone (PR) receptors positive: 321 (63%), axillary lymph nodes positive: 266 (52%), Adj T: 386 (76%), neoAdj T: 120 (24%), Tax- and Tax/Anthra–based AdjTx: 457 (90%), non-Tax/non-Anthra AdjTx and single-agent T (without chemotherapy): 49 (10%). Median FU is 73.3 months (range: 1.4-176.3). In the overall population, DFS and OS rates are 83% and 91%, respectively. Pts treated with non-Tax/non-Anthra AdjTx had a significantly higher risk of BrCa relapse [DFS: HR 3.54 (95%CI:1.24 to 10.06, p=0.018)], and death [OS: HR 2.73 (95%CI:0.63 to 11.77 p=0.176)] compared to those treated with Tax–based AdjTx (e.g. TCH [docetaxel/carboplatin/T]). Pts who received single-agent T also had highly significantly worse DFS [HR 4.21 (95%CI:2.18 to 8.38, p&amp;lt;0.0001)] and OS [HR 6.75 (95%CI:3.13 to 14.6 p=&amp;lt;0.0001)] compared to those treated with Tax-based AdjTx. When adjusted for age (&amp;lt;55 vs &amp;gt;55 yrs), the detrimental impact of type of AdjTx remained highly statistically significant (p&amp;lt;0.0001). Patients with TTE&amp;lt;24 weeks had a highly significantly worse DFS [HR 4.7 (95%CI:2.34-9.47, p&amp;lt;0.0001)] and OS [HR 5.36 (95%CI:2.39-12.01, p&amp;lt;0.0001)] compared to pts with TTE&amp;gt;24weeks. In most cases, shorter duration of T was due to reduction in LVEF or patients refusal. In the multivariate model, positive lymph nodes, type of (neo)AdjTx and TET (&amp;lt;24 weeks vs &amp;gt;24 weeks) remained all significant and independent variables associated with worse DFS and OS. Conclusions Our mature results indicate that the administration of non-Tax/non-Anthra-based AdjTx and single-agent T is associated with a significant increase in the risk of disease relapse and death and should not be considered as therapeutic options for pts with HER2+ ESBrCa. The administration of T for &amp;lt;24weeks irrespective of the type of AdjTx is also associated with significantly worse outcome. Citation Format: Gullo G, Walsh N, Fennelly D, Walshe J, O'Mahony K, Silva N, Ballot J, Calzaferri G, Quinn C, McDonnell D, Crown J. Impact of type of (neo)adjuvant systemic therapy (AdjTx) and total exposure to trastuzumab (TET) on long-term outcome of HER2-positive (HER2+) early stage breast cancer (ESBrCa) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-20-05.