Cardiac function in BRCA1/2 mutation carriers with history of breast cancer treated with anthracyclines.

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Citation: Breast Cancer Research & Treatment. 155(2):285-93, 2016 Jan.PMID: 26749359Institution: MedStar Health Research Institute | MedStar Health Research Institute | MedStar Health Research Institute | MedStar Washington Hospital Center | MedStar Washington Hospital Center | Washington Cancer Institute | Washington Cancer Institute | Washington Cancer Institute A | Washington Cancer InstituteiaDepartment: MedStar Heart Institute | MedStar Heart InstituteForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Anthracyclines/ae [Adverse Effects] | *Anthracyclines/tu [Therapeutic Use] | *BRCA1 Protein/ge [Genetics] | *BRCA2 Protein/ge [Genetics] | *Breast Neoplasms/dt [Drug Therapy] | *Breast Neoplasms/pa [Pathology] | *Ventricular Function, Left/de [Drug Effects] | Adult | Breast Neoplasms/ge [Genetics] | Doxorubicin/tu [Therapeutic Use] | Female | Humans | Middle Aged | Mutation/ge [Genetics] | Prospective Studies | Stroke Volume/de [Drug Effects]Year: 2016ISSN:
  • 0167-6806
Name of journal: Breast cancer research and treatmentAbstract: 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.All authors: Asch 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 LFiscal year: 2016Date added to catalog: 2017-03-06
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Journal Article MedStar Authors Catalog Article 26749359 Available 26749359

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.

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