Abstract P4-10-16: Long term effects of trastuzumab on cardiopulmonary and left ventricular function in women with HER2 overexpressing breast cancer
Authors: Pituskin E , Paterson I , Ghosh S , Mackey JR , Haykowsky MJ 
Published: May 2016

Background: Adjuvant trastuzumab (TRZ) is the standard of care for HER2-overexpressing (HER2+) early stage breast cancer (EBC) patients (PTS), with five-year survival rates exceeding 90%. However, significant cardiac toxicities are observed, with a fivefold increase in clinical heart failure (HF). Left ventricular (LV) remodeling (increased heart size and mass) is an early indicator of cardiac injury, progressing to further LV dysfunction, reduced exercise tolerance and overt HF. Therefore, effective prevention of such negative sequelae is of enormous clinical interest. As the pivotal TRZ trials assessed cardiac function with MUGA or echocardiography, insensitive modalities to evaluate LV remodeling, the long-term sequelae of TRZ remain unknown.

Objective: to determine the long term effects of trastuzumab on cardiopulmonary and left ventricular function in women with HER2 overexpressing breast cancer. Additionally as aerobic training is an effective intervention in HF PTS who adhere to prescribed exercise, a sub-analysis compared those who adhered during a 4 month exercise intervention (AEX) vs those who did not adhere (NEX).

Methods: 16 PTS (mean age 58 ± 7) who participated in an exercise intervention study during the first 4 months of TRZ therapy were recruited, with an average of 4 years elapsing since TRZ completion. Cardiopulmonary exercise (VO2peak) testing and resting cardiac MRI (CMR) were performed and compared with baseline and 4 month assessments. Adherence to exercise intevention was defined as attendance ≥80% prescribed sessions.

Results: All 16 PTS reported independent living with no limitations to ADLs. At 4 years, mean VO2peak for all PTS was 22.4 ml/kg/min (20.0 at baseline and 22.0 at 4 months). In AEX PTS, higher VO2peak persisted 4 years after cessation of therapy, 4.1 mL/kg/min higher than NEX PTS (24.9 and 20.8 mL/kg/min, respectively ). Mean LVEF for all PTS was 60 ± 6%, not significantly different from baseline or 4 months (61 ± 5 and 55 ± 4%, respectively) . Statistically significant interactions of exercise adherence to other CMR metrics were not observed.

Conclusions: Clinically significant impairment of cardiopulmonary function (equal to 14 years of aging) are present before therapy and persist in PTS four years following exposure to TRZ-based chemotherapy. This observation is consistent with our other work, and occurs on a background of normal LVEF, implying additional negative effects to other components of the oxygen cascade. As mortality risk has been shown to decrease by 17% for every 3.5 mL/kg/min difference in aerobic capacity in healthy females, these findings indicate adherence to exercise interventions during TRZ-based therapy has potentially important long-term implications.

Citation Format: Pituskin E, Paterson I, Ghosh S, Mackey JR, Haykowsky MJ. Long term effects of trastuzumab on cardiopulmonary and left ventricular function in women with HER2 overexpressing breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-10-16.