Abstract P1-03-01: Cardiac function in BRCA1/2 mutation carriers with a history of breast cancer (BC) treated with anthracyclines (anthra)
Authors: Lynce Filipa , Barac Ana , Smith Karen L , Mete Mihriye , Wray Lynette , Nardacci Madeline , Herbolsheimer Pia , Nunes Raquel , Swain Sandra M , Warren Robert , Isaacs Claudine 
Published: May 2015

Introduction: Animal data suggest that cardiac-specific loss of BRCA1/2 genes leads to increased cardiac dysfunction in the setting of stressors such as ischemia or anthra chemotherapy (CT). Women with BRCA1/2 mutations who develop BC may receive anthra-based CT. It is not known whether BRCA1/2 mutation carriers treated for early stage BC with anthra-based CT are at higher risk for anthra-induced cardiac toxicity than similarly treated women with sporadic BC. This study investigates left ventricular ejection fraction (LVEF) and myocardial global longitudinal strain (GLS), a novel echocardiographic measure of cardiac contractility, in women with and without BRCA1/2 mutations who were treated with anthra-based CT.

Methods: We identified 41 women with a history of BRCA1/2 mutation-associated BC and 52 women with a history of sporadic BC, all of whom received anthra-based adjuvant or neoadjuvant CT. We excluded women who received HER2 therapy or who had stage IV disease. BC CT was completed at least 6 months prior to study enrollment. All participants completed a cardiac questionnaire and underwent a comprehensive 2D and 3D echocardiographic exam with assessment of myocardial GLS using speckle-tracking software (QLAB10, Philips, Andover, MA). Abnormal LVEF was defined as less than 55% (50-54.9% borderline reduced and 40-49% mildly reduced) and abnormal GLS was defined as absolute value of less than 18.9%. Patients with history of hypertension (HTN) were excluded from this analysis to avoid confounding effects of HTN on GLS.

Results: We present data on 57 normotensive participants, 34 BRCA1/2 mutation-carriers and 23 non-mutation carriers. Mean age was 49.5 +/- 8.7 years in the BRCA mutation-carrier group and 51.1 +/- 8.7 years in the non-mutation carrier group (p=0.496). Women with BRCA1/2 mutations were more likely to be Caucasian (p=0.026) and have undergone oophorectomy (p&lt;0.001). The average time from anthra treatment to study enrollment was 5 +/- 4.4 years. Groups were well balanced with regards to age, diabetes, hyperlipidemia, history of coronary disease, smoking and cumulative dose of anthra. Four BRCA1/2 mutation-carriers (12%) and 4 non-mutation carriers (17%) had reduced GLS (p= 0.450). Mean LVEF was similar between the groups: LVEF was borderline reduced in one BRCA1/2 mutation-carrier (3%) and borderline or mildly reduced in 4 non-mutation carriers (18%)(p= 0.091).

Conclusions: In this population, reduced LVEF and myocardial GLS were present in a small percentage of women treated with anthra-based CT for early stage BC. However, reduction in LVEF and myocardial GLS did not differ between the BRCA1/2 mutation carriers and the women with a history of sporadic BC. Larger studies are needed to definitively rule out a difference in cardiac toxicity by BRCA mutation status in BC survivors treated with anthra. This project is supported by Fisher Center for Familial Cancer Research Award at Lombardi Comprehensive Cancer Center. AB is supported by Georgetown-Howard Universities Center for Clinical & Translational Science (GHUCCTS) post-doctoral KL2 Award (5KL2TR000102-04).

Citation Format: Filipa Lynce, Ana Barac, Karen L Smith, Mihriye Mete, Lynette Wray, Madeline Nardacci, Pia Herbolsheimer, Raquel Nunes, Sandra M Swain, Robert Warren, Claudine Isaacs. Cardiac function in BRCA1/2 mutation carriers with a history of breast cancer (BC) treated with anthracyclines (anthra) [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 P1-03-01.