TY  - BOOK
AU  - Asch, Federico M
AU  - Barac, Ana
AU  - Herbolsheimer, Pia M
AU  - Lynce, Filipa
AU  - Mete, Mihriye
AU  - Nunes, Raquel
AU  - Shara, Nawar M
AU  - Swain, Sandra M
AU  - Wray, Lynette
TI  - Cardiac function in BRCA1/2 mutation carriers with history of breast cancer treated with anthracyclines
SN  - 0167-6806
KW  - *Anthracyclines/ae [Adverse Effects]
KW  - *Anthracyclines/tu [Therapeutic Use]
KW  - *BRCA1 Protein/ge [Genetics]
KW  - *BRCA2 Protein/ge [Genetics]
KW  - *Breast Neoplasms/dt [Drug Therapy]
KW  - *Breast Neoplasms/pa [Pathology]
KW  - *Ventricular Function, Left/de [Drug Effects]
KW  - Adult
KW  - Breast Neoplasms/ge [Genetics]
KW  - Doxorubicin/tu [Therapeutic Use]
KW  - Female
KW  - Humans
KW  - Middle Aged
KW  - Mutation/ge [Genetics]
KW  - Prospective Studies
KW  - Stroke Volume/de [Drug Effects]
KW  - MedStar Health Research Institute
KW  - MedStar Washington Hospital Center
KW  - Washington Cancer Institute
KW  - Washington Cancer Institute A
KW  - Washington Cancer Instituteia
KW  - MedStar Heart Institute
KW  - Journal Article
N2  - Animal data suggest that defects in BRCA1/2 genes significantly increase the risk of heart failure and mortality in mice exposed to doxorubicine. Women with BRCA1/2 mutations who develop breast cancer (BC) may receive anthracyclines but their risk of cardiac dysfunction has not been investigated. Our study tested the hypothesis that women with history of BRCA1/2 mutation-associated BC treated with anthracyclines have impaired parameters of cardiac function compared to similarly treated women with history of sporadic BC. Women with history of BC and anthracycline treatment underwent an echocardiographic exam for assessment of primary outcomes, left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). The sample size of 81 provided 79 % power with two-sided two-sample t test and alpha of 0.05 to detect a clinically meaningful difference in cardiac function of absolute 5 % points difference for LVEF and 2 % points difference for GLS. Of 81 normotensive participants, 39 were BRCA1/2 mutation carriers and 42 in the sporadic group. Mean age was 50 +/- 9 years in both groups (P = 0.99) but BRCA1/2 mutation carriers had longer anthracycline treatment-to-enrollment time (7.5 +/- 5.3 vs. 4.2 +/- 3.3 years, P = 0.001). There were no significant differences in LVEF (P = 0.227) or GLS (P = 0.53) between the groups. LVEF was normal in 91 % of women and subclinical cardiac dysfunction defined as absolute GLS value <18.9 % was seen in 4 (10 %) BRCA1/2 mutation carriers and 7 (17 %) sporadic participants. In this first prospective examination of cardiac function in BRCA1/2 mutation carriers, we found no significant differences in sensitive echocardiographic parameters of cardiac function between BRCA1/2 mutation carriers and women with history of sporadic BC who received anthracycline treatment. In contrast to laboratory animal data, our findings indicate lack of elevated cardiac risk with the use of standard-doses of adjuvant anthracyclines in treatment of BRCA1/2 mutation carriers with early stage BC
ER  -