title: Cardiac function in BRCA1/2 mutation carriers with history of breast cancer treated with anthracyclines.
abstract: 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.
authors.affiliation: Division of Cardiology, MedStar Washington Hospital Center, MedStar Heart and Vascular Institute, 110 Irving Street, NW, Suite F1218, Washington DC, 20010, USA. Ana.Barac@medstar.net.|Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA. Ana.Barac@medstar.net.
authors.forename: Ana
authors.initials: A
authors.lastname: Barac
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA.|Division of Oncology, MedStar Georgetown University Hospital, Washington DC, USA.
authors.forename: Filipa
authors.initials: F
authors.lastname: Lynce
authors.affiliation: Johns Hopkins Kimmel Cancer Center, Sibley Memorial Hospital, Washington DC, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Smith
authors.affiliation: MedStar Health Research Institute, Washington DC, USA.
authors.forename: Mihriye
authors.initials: M
authors.lastname: Mete
authors.affiliation: MedStar Health Research Institute, Washington DC, USA.
authors.forename: Nawar M
authors.initials: NM
authors.lastname: Shara
authors.affiliation: Division of Cardiology, MedStar Washington Hospital Center, MedStar Heart and Vascular Institute, 110 Irving Street, NW, Suite F1218, Washington DC, 20010, USA.|MedStar Health Research Institute, Washington DC, USA.
authors.forename: Federico M
authors.initials: FM
authors.lastname: Asch
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA.
authors.forename: Madeline P
authors.initials: MP
authors.lastname: Nardacci
authors.affiliation: MedStar Health Research Institute, Washington DC, USA.
authors.forename: Lynette
authors.initials: L
authors.lastname: Wray
authors.affiliation: Division of Oncology, MedStar Washington Hospital Center, Washington DC, USA.
authors.forename: Pia
authors.initials: P
authors.lastname: Herbolsheimer
authors.affiliation: Division of Oncology, MedStar Washington Hospital Center, Washington DC, USA.
authors.forename: Raquel A
authors.initials: RA
authors.lastname: Nunes
authors.affiliation: Division of Oncology, MedStar Washington Hospital Center, Washington DC, USA.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Swain
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA.|Division of Oncology, MedStar Georgetown University Hospital, Washington DC, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Warren
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA.
authors.forename: Beth N
authors.initials: BN
authors.lastname: Peshkin
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA.|Division of Oncology, MedStar Georgetown University Hospital, Washington DC, USA.
authors.forename: Claudine
authors.initials: C
authors.lastname: Isaacs
mesh_terms: D000328:Adult; D018943:Anthracyclines / Q000009:adverse effects* / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011446:Prospective Studies; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D018943:Anthracyclines; D019313:BRCA1 Protein; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004317:Doxorubicin
keywords: Anthracycline; BRCA1/2 mutation; Breast cancer; Cardiotoxicity; Echocardiography