000			04372nam a22006737a 4500
008			161101s20162016 xxu||||| |||| 00| 0 eng d
022			_a0167-6806
040			_aOvid MEDLINE(R)
099			_a26749359
245			_aCardiac function in BRCA1/2 mutation carriers with history of breast cancer treated with anthracyclines.
251			_aBreast Cancer Research & Treatment. 155(2):285-93, 2016 Jan.
252			_aBreast Cancer Res Treat. 155(2):285-93, 2016 Jan.
253			_aBreast cancer research and treatment
260			_92016 Jan
260			_c2016
260			_f2016
266			_d2017-03-06
520			_aAnimal 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.
546			_aEnglish
650			_a*Anthracyclines/ae [Adverse Effects]
650			_a*Anthracyclines/tu [Therapeutic Use]
650			_a*BRCA1 Protein/ge [Genetics]
650			_a*BRCA2 Protein/ge [Genetics]
650			_a*Breast Neoplasms/dt [Drug Therapy]
650			_a*Breast Neoplasms/pa [Pathology]
650			_a*Ventricular Function, Left/de [Drug Effects]
650			_aAdult
650			_aBreast Neoplasms/ge [Genetics]
650			_aDoxorubicin/tu [Therapeutic Use]
650			_aFemale
650			_aHumans
650			_aMiddle Aged
650			_aMutation/ge [Genetics]
650			_aProspective Studies
650			_aStroke Volume/de [Drug Effects]
651			_aMedStar Health Research Institute
651			_aMedStar Health Research Institute
651			_aMedStar Health Research Institute
651			_aMedStar Washington Hospital Center
651			_aMedStar Washington Hospital Center
651			_aWashington Cancer Institute
651			_aWashington Cancer Institute
651			_aWashington Cancer Institute A
651			_aWashington Cancer Instituteia
656			_aMedStar Heart Institute
656			_aMedStar Heart Institute
657			_aJournal Article
700			_aAsch, Federico M
700			_aBarac, Ana
700			_aHerbolsheimer, Pia M
700			_aLynce, Filipa
700			_aMete, Mihriye
700			_aNunes, Raquel
700			_aShara, Nawar M
700			_aSwain, Sandra M
700			_aWray, Lynette
790			_aAsch FM, Barac A, Herbolsheimer P, Isaacs C, Lynce F, Mete M, Nardacci MP, Nunes RA, Peshkin BN, Shara NM, Smith KL, Swain SM, Warren R, Wray L
942			_cART _dArticle
999			_c1976 _d1976