The impact of mild left ventricular dysfunction on trastuzumab use and oncologic outcomes in early stage breast cancer therapy.

Abstract

e18148 Background: Trastuzumab (T) significantly reduces the risk of breast cancer recurrence, but may be associated with an increased incidence of heart failure. The intention of this study was to assess how T therapy was managed after the development of mild left ventricular ejection fraction (LVEF) drop in a non-trial setting and to evaluate the cardiovascular and oncologic outcomes. Methods: Patients (pts) who received adjuvant T therapy in British Columbia for breast cancer between September 2005 and December 2013 were identified. Pts were eligible if they had a drop in LVEF to 40-49% after starting T. Charts were reviewed for demographic information. Pts were divided into 2 cohorts: those who continued T without interruption, and those who had any interruption or discontinuation. Breast cancer outcomes and cardiac outcomes were compared in each of these groups. Results: Of the 2401 pts who were screened, 261 (10.9%) pts had a drop in LVEF to 40-49%. Of these, 229 (87.7%) had an interruption in T, while 32 (12.3%) did not have an interruption in therapy. The number of pts who experienced a cancer relapse in the T interruption and continuous groups were 38 (16.6%) and 2 (6.25%), respectively (P = 0.19). Even amongst those who received a full 17 cycles of therapy, there was a 11.25% absolute increase in the risk of breast cancer recurrence (17.5% vs 6.25%) in those who had an interruption in their course of treatment compared to those who did not have an interruption (p = 0.15). Cardiac outcomes (subsequent LVEF drop < 40% or CHF) were higher in the group of pts who had treatment interrupted compared to those who had continuation of T (14.8% vs 0%). Conclusions: Interrupting T after the development of mild left ventricular dysfunction was associated with a 10.35% (p = 0.19) absolute increase in breast cancer recurrence. Continuing T was not associated with an increased risk of long term cardiovascular events. While these results are not statistically significant, they are concerning and warrant further investigation.

Does trastuzumab-related cardiotoxicity influence long-term outcome in patients with HER-2 positive breast cancer? A prospective study

“…Early discontinuation was associated with higher cancer recurrence. Similar results were revealed in a retrospective chart re- view of 2401 patients, in whom there was nearly a three-fold increase in risk of breast cancer recurrence if they had had an interruption in the course of trastuzumab treatment (17.5% vs. 6.3%) [27].…”

“…One retrospective study showed that 5 years after the completion of breast cancer treatment 12% of women who had received trastuzumab alone and over 20% who had received trastuzumab following anthracyclines were diagnosed with heart failure or cardiomyopathy [13]. In another retrospective analysis from Denmark, 5 years after trastuzumab completion the risk of heart failure development among patients treated with chemotherapy-plus-trastuzumab compared with those treated with chemotherapy alone increased two-fold [27]. In one prospective observation heart remodelling (left ventricle and left atrium enlargement) was found in a substantial number of women 6 months after the completion of BC chemotherapy consisting of anthracyclines and trastuzumab [21].…”

Adjuvant Trastuzumab Therapy: Can We Balance Efficacy and Safety?

“…There is emerging evidence that regardless of the optimal target duration of trastuzumab, interruptions of therapy may be associated with poorer outcomes. A retrospective chart review of 2,401 patients aiming to complete 17 cycles of trastuzumab showed that there was nearly a 3‐fold increase in risk of breast cancer recurrence (17.5% vs. 6.25%) in patients who had an interruption in their course of treatment compared with those who did not . Ultimately, the risk of cardiotoxicity must be weighed against the survival benefits associated with continuing trastuzumab at the level of each individual patient.…”