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Cardiac function in BRCA1/2 mutation carriers with history of breast cancer treated with anthracyclines
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. Ou...
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| Published in: | Breast cancer research and treatment 2016-01, Vol.155 (2), p.285-293 |
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| container_title | Breast cancer research and treatment |
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| creator | Barac, Ana Lynce, Filipa Smith, Karen L. Mete, Mihriye Shara, Nawar M. Asch, Federico M. Nardacci, Madeline P. Wray, Lynette Herbolsheimer, Pia Nunes, Raquel A. Swain, Sandra M. Warren, Robert Peshkin, Beth N. Isaacs, Claudine |
| description | 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 |
| doi_str_mv | 10.1007/s10549-016-3678-2 |
| format | article |
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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.</description><identifier>ISSN: 0167-6806</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-016-3678-2</identifier><identifier>PMID: 26749359</identifier><identifier>CODEN: BCTRD6</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adjuvant chemotherapy ; Adult ; Anthracyclines ; Anthracyclines - adverse effects ; Anthracyclines - therapeutic use ; BRCA1 Protein - genetics ; BRCA2 Protein - genetics ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Cancer research ; Cancer therapies ; Cardiovascular disease ; Chemotherapy ; Clinical Trial ; Comparative analysis ; Development and progression ; Doxorubicin - therapeutic use ; Female ; Health aspects ; Heart ; Heart failure ; Humans ; Medicine ; Medicine & Public Health ; Middle Aged ; Mutation ; Mutation - genetics ; Oncology ; Prospective Studies ; Side effects ; Stroke Volume - drug effects ; Toxicity ; Ventricular Function, Left - drug effects</subject><ispartof>Breast cancer research and treatment, 2016-01, Vol.155 (2), p.285-293</ispartof><rights>Springer Science+Business Media New York 2016</rights><rights>COPYRIGHT 2016 Springer</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c573t-85c0ac0ac19a14b5269eb21e41568861c61ca1da1207a2104a0b5694267e8df73</citedby><cites>FETCH-LOGICAL-c573t-85c0ac0ac19a14b5269eb21e41568861c61ca1da1207a2104a0b5694267e8df73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26749359$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Barac, Ana</creatorcontrib><creatorcontrib>Lynce, Filipa</creatorcontrib><creatorcontrib>Smith, Karen L.</creatorcontrib><creatorcontrib>Mete, Mihriye</creatorcontrib><creatorcontrib>Shara, Nawar M.</creatorcontrib><creatorcontrib>Asch, Federico M.</creatorcontrib><creatorcontrib>Nardacci, Madeline P.</creatorcontrib><creatorcontrib>Wray, Lynette</creatorcontrib><creatorcontrib>Herbolsheimer, Pia</creatorcontrib><creatorcontrib>Nunes, Raquel A.</creatorcontrib><creatorcontrib>Swain, Sandra M.</creatorcontrib><creatorcontrib>Warren, Robert</creatorcontrib><creatorcontrib>Peshkin, Beth N.</creatorcontrib><creatorcontrib>Isaacs, Claudine</creatorcontrib><title>Cardiac function in BRCA1/2 mutation carriers with history of breast cancer treated with anthracyclines</title><title>Breast cancer research and treatment</title><addtitle>Breast Cancer Res Treat</addtitle><addtitle>Breast Cancer Res Treat</addtitle><description>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.</description><subject>Adjuvant chemotherapy</subject><subject>Adult</subject><subject>Anthracyclines</subject><subject>Anthracyclines - adverse effects</subject><subject>Anthracyclines - therapeutic use</subject><subject>BRCA1 Protein - genetics</subject><subject>BRCA2 Protein - genetics</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Cardiovascular disease</subject><subject>Chemotherapy</subject><subject>Clinical Trial</subject><subject>Comparative analysis</subject><subject>Development and progression</subject><subject>Doxorubicin - therapeutic use</subject><subject>Female</subject><subject>Health aspects</subject><subject>Heart</subject><subject>Heart failure</subject><subject>Humans</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Mutation - genetics</subject><subject>Oncology</subject><subject>Prospective Studies</subject><subject>Side effects</subject><subject>Stroke Volume - drug effects</subject><subject>Toxicity</subject><subject>Ventricular Function, Left - drug effects</subject><issn>0167-6806</issn><issn>1573-7217</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNp1kl2L1TAQhoMo7nH1B3gjBUG86W4mTfNxeTz4BQuC6HVI0_Q0S5usSYqcf29qV90VJQMhM887zEwGoeeALwBjfpkAt1TWGFjdMC5q8gDtoOVNzQnwh2hXArxmArMz9CSla4yx5Fg-RmeEcSqbVu7Q8aBj77SphsWb7IKvnK_efD7s4ZJU85L1T5_RMTobU_Xd5bEaXcohnqowVF20OuUS98bGKpdXtv1GaZ_HqM3JTM7b9BQ9GvSU7LPb-xx9fff2y-FDffXp_cfD_qo2pe5ci9ZgvRpIDbRrCZO2I2AptEwIBqaYhl4DwVwTwFTjrmWSloas6AfenKPXW96bGL4tNmU1u2TsNGlvw5IUCE4EJWUSBX35F3odluhLdQo4w5wQAPGHOurJKueHkEtXa1K1p5QISRtOCnXxD6qc3s7OBG8HV_z3BK_uCEarpzymMC3ruNN9EDbQxJBStIO6iW7W8aQAq3UL1LYFqny2WrdArZoXt50t3Wz734pf314AsgGphPzRxjut_zfrD00luU8</recordid><startdate>20160101</startdate><enddate>20160101</enddate><creator>Barac, Ana</creator><creator>Lynce, Filipa</creator><creator>Smith, Karen L.</creator><creator>Mete, Mihriye</creator><creator>Shara, Nawar M.</creator><creator>Asch, Federico M.</creator><creator>Nardacci, Madeline P.</creator><creator>Wray, Lynette</creator><creator>Herbolsheimer, Pia</creator><creator>Nunes, Raquel A.</creator><creator>Swain, Sandra M.</creator><creator>Warren, Robert</creator><creator>Peshkin, Beth N.</creator><creator>Isaacs, Claudine</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20160101</creationdate><title>Cardiac function in BRCA1/2 mutation carriers with history of breast cancer treated with anthracyclines</title><author>Barac, Ana ; Lynce, Filipa ; Smith, Karen L. ; Mete, Mihriye ; Shara, Nawar M. ; Asch, Federico M. ; Nardacci, Madeline P. ; Wray, Lynette ; Herbolsheimer, Pia ; Nunes, Raquel A. ; Swain, Sandra M. ; Warren, Robert ; Peshkin, Beth N. ; Isaacs, Claudine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c573t-85c0ac0ac19a14b5269eb21e41568861c61ca1da1207a2104a0b5694267e8df73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adjuvant chemotherapy</topic><topic>Adult</topic><topic>Anthracyclines</topic><topic>Anthracyclines - adverse effects</topic><topic>Anthracyclines - therapeutic use</topic><topic>BRCA1 Protein - genetics</topic><topic>BRCA2 Protein - genetics</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - pathology</topic><topic>Cancer research</topic><topic>Cancer therapies</topic><topic>Cardiovascular disease</topic><topic>Chemotherapy</topic><topic>Clinical Trial</topic><topic>Comparative analysis</topic><topic>Development and progression</topic><topic>Doxorubicin - therapeutic use</topic><topic>Female</topic><topic>Health aspects</topic><topic>Heart</topic><topic>Heart failure</topic><topic>Humans</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Mutation - genetics</topic><topic>Oncology</topic><topic>Prospective Studies</topic><topic>Side effects</topic><topic>Stroke Volume - drug effects</topic><topic>Toxicity</topic><topic>Ventricular Function, Left - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barac, Ana</creatorcontrib><creatorcontrib>Lynce, Filipa</creatorcontrib><creatorcontrib>Smith, Karen L.</creatorcontrib><creatorcontrib>Mete, Mihriye</creatorcontrib><creatorcontrib>Shara, Nawar M.</creatorcontrib><creatorcontrib>Asch, Federico M.</creatorcontrib><creatorcontrib>Nardacci, Madeline P.</creatorcontrib><creatorcontrib>Wray, Lynette</creatorcontrib><creatorcontrib>Herbolsheimer, Pia</creatorcontrib><creatorcontrib>Nunes, Raquel A.</creatorcontrib><creatorcontrib>Swain, Sandra M.</creatorcontrib><creatorcontrib>Warren, Robert</creatorcontrib><creatorcontrib>Peshkin, Beth N.</creatorcontrib><creatorcontrib>Isaacs, Claudine</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database (Proquest)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Family Health Database (Proquest)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Breast cancer research and treatment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barac, Ana</au><au>Lynce, Filipa</au><au>Smith, Karen L.</au><au>Mete, Mihriye</au><au>Shara, Nawar M.</au><au>Asch, Federico M.</au><au>Nardacci, Madeline P.</au><au>Wray, Lynette</au><au>Herbolsheimer, Pia</au><au>Nunes, Raquel A.</au><au>Swain, Sandra M.</au><au>Warren, Robert</au><au>Peshkin, Beth N.</au><au>Isaacs, Claudine</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cardiac function in BRCA1/2 mutation carriers with history of breast cancer treated with anthracyclines</atitle><jtitle>Breast cancer research and treatment</jtitle><stitle>Breast Cancer Res Treat</stitle><addtitle>Breast Cancer Res Treat</addtitle><date>2016-01-01</date><risdate>2016</risdate><volume>155</volume><issue>2</issue><spage>285</spage><epage>293</epage><pages>285-293</pages><issn>0167-6806</issn><eissn>1573-7217</eissn><coden>BCTRD6</coden><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.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>26749359</pmid><doi>10.1007/s10549-016-3678-2</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0167-6806 |
| ispartof | Breast cancer research and treatment, 2016-01, Vol.155 (2), p.285-293 |
| issn | 0167-6806 1573-7217 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1872842009 |
| source | Springer Nature |
| subjects | Adjuvant chemotherapy Adult Anthracyclines Anthracyclines - adverse effects Anthracyclines - therapeutic use BRCA1 Protein - genetics BRCA2 Protein - genetics Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - genetics Breast Neoplasms - pathology Cancer research Cancer therapies Cardiovascular disease Chemotherapy Clinical Trial Comparative analysis Development and progression Doxorubicin - therapeutic use Female Health aspects Heart Heart failure Humans Medicine Medicine & Public Health Middle Aged Mutation Mutation - genetics Oncology Prospective Studies Side effects Stroke Volume - drug effects Toxicity Ventricular Function, Left - drug effects |
| title | Cardiac function in BRCA1/2 mutation carriers with history of breast cancer treated with anthracyclines |
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