Abstract P4-21-38: Cardiac safety of dual anti-HER2 therapy in the neoadjuvant setting for treatment of HER2-positive breast cancer
Authors: Yu AF , Wang R , Singh J , Liu JE , Eaton A , Jones L , Oeffinger K , Steingart RM , Hudis CA , Dang CT 
Published: March 2017

Abstract
Background: Trastuzumab and pertuzumab are approved for the treatment of HER2-postiive breast cancer in the neoadjuvant setting. However, limited cardiac safety data is available when used in combination with doxorubicin-based chemotherapy. At a single center we retrospectively report the cardiac safety of dose-dense doxorubicin and cyclophosphamide (AC) followed by paclitaxel, trastuzumab, and pertuzumab (THP) in the neoadjuvant setting followed by adjuvant trastuzumab-based therapy.
Methods: Patients treated with neoadjuvant dose dense AC followed by THP from September 1, 2014 to March 1, 2015 were retrospectively identified. Patients then had breast surgery and completion of anti-HER2 therapy for 1 year. The primary outcome was cardiac event rate, defined by New York Heart Association (NYHA) class III/IV or cardiac death. The secondary outcome was significant asymptomatic decline in left ventricular ejection fraction (LVEF) of 10%-15% from baseline to below the lower limit of normal, or &gt; 16% from baseline. Patients underwent LVEF monitoring at baseline prior to AC, prior to initiation of THP, and serially during 1 year of anti-HER2 therapy (neoadjuvant to adjuvant phases).
Results: Fifty-seven patients were included in the study. The median age was 46 years (range 26-68 years). The median number of cycles of trastuzumab and pertuzumab in the neoadjvuvant setting was 6 (range 3-8) and 6 (range 2-8), respectively. In the adjuvant setting, 56 (98%) patients received trastuzumab with pertuzumab with a median cycle number of 12 (range 1-13). Two of 57 (3.5%) patients developed NYHA class III/IV heart failure after 5 and 9 months of trastuzumab, leading to permanent discontinuation of anti-HER2 treatment. Additionally, 7 (12.3%) patients developed a significant LVEF decline (without severe HF symptoms). The median LVEF was 65% (range 55-75%) at baseline and 64% (range 53-72%) after AC. There was a reduction in median LVEF to 60% (range 35-70%), 60% (range 23- 73%), 61% (range 25-73%), and 58% (range 28-66%) at 3, 6, 9, and 12 months (+/- 6 weeks) of trastuzumab-based therapy.

Conclusion: In patients with HER2-positive breast cancer treated with neoadjuvant dose-dense AC and THP followed by completion of anti-HER2 therapy in adjuvant setting, the overall rate of NYHA Class III/IV heart failure was comparable to rates reported in trials of sequential doxorubicin and trastuzumab. Our findings do not suggest an increased risk of cardiotoxicity when pertuzumab is added to trastuzumab following a doxorubicin-based regimen.
Citation Format: Yu AF, Wang R, Singh J, Liu JE, Eaton A, Jones L, Oeffinger K, Steingart RM, Hudis CA, Dang CT. Cardiac safety of dual anti-HER2 therapy in the neoadjuvant setting for treatment of HER2-positive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-38.