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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en"><italic>CYP19A1</italic> polymorphisms and clinical outcomes in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1–98 trial</title><author><name sortKey="Leyland Jones, Brian" sort="Leyland Jones, Brian" uniqKey="Leyland Jones B" first="Brian" last="Leyland-Jones">Brian Leyland-Jones</name><affiliation><nlm:aff id="A1">Avera Cancer Institute, 1000 E 23rd Street, Sioux Falls, SD 57105, USA</nlm:aff></affiliation></author><author><name sortKey="Gray, Kathryn P" sort="Gray, Kathryn P" uniqKey="Gray K" first="Kathryn P." last="Gray">Kathryn P. Gray</name><affiliation><nlm:aff id="A2">International Breast Cancer Study Group (IBCSG) Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Abramovitz, Mark" sort="Abramovitz, Mark" uniqKey="Abramovitz M" first="Mark" last="Abramovitz">Mark Abramovitz</name><affiliation><nlm:aff id="A4">VM Institute of Research, Montreal, QC, Canada</nlm:aff></affiliation></author><author><name sortKey="Bouzyk, Mark" sort="Bouzyk, Mark" uniqKey="Bouzyk M" first="Mark" last="Bouzyk">Mark Bouzyk</name><affiliation><nlm:aff id="A5">AKESOgen, Inc., Norcross, GA, USA</nlm:aff></affiliation></author><author><name sortKey="Young, Brandon" sort="Young, Brandon" uniqKey="Young B" first="Brandon" last="Young">Brandon Young</name><affiliation><nlm:aff id="A1">Avera Cancer Institute, 1000 E 23rd Street, Sioux Falls, SD 57105, USA</nlm:aff></affiliation></author><author><name sortKey="Long, Bradley" sort="Long, Bradley" uniqKey="Long B" first="Bradley" last="Long">Bradley Long</name><affiliation><nlm:aff id="A6">Genomic Molecular Pathology, Department of Pathology, University of Chicago, Chicago, IL, USA</nlm:aff></affiliation></author><author><name sortKey="Kammler, Roswitha" sort="Kammler, Roswitha" uniqKey="Kammler R" first="Roswitha" last="Kammler">Roswitha Kammler</name><affiliation><nlm:aff id="A7">IBCSG Coordinating Center and Central Pathology Office, Bern, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Dell Orto, Patrizia" sort="Dell Orto, Patrizia" uniqKey="Dell Orto P" first="Patrizia" last="Dell'Orto">Patrizia Dell'Orto</name><affiliation><nlm:aff id="A8">IBCSG Central Pathology Office, Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Biasi, Maria Olivia" sort="Biasi, Maria Olivia" uniqKey="Biasi M" first="Maria Olivia" last="Biasi">Maria Olivia Biasi</name><affiliation><nlm:aff id="A9">Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Thurlimann, Beat" sort="Thurlimann, Beat" uniqKey="Thurlimann B" first="Beat" last="Thürlimann">Beat Thürlimann</name><affiliation><nlm:aff id="A10">Breast Center, Kantonsspital, St. Gallen, Switzerland</nlm:aff></affiliation><affiliation><nlm:aff id="A11">Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Lyng, Maria B" sort="Lyng, Maria B" uniqKey="Lyng M" first="Maria B." last="Lyng">Maria B. Lyng</name><affiliation><nlm:aff id="A12">Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark</nlm:aff></affiliation></author><author><name sortKey="Ditzel, Henrik J" sort="Ditzel, Henrik J" uniqKey="Ditzel H" first="Henrik J." last="Ditzel">Henrik J. Ditzel</name><affiliation><nlm:aff id="A12">Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark</nlm:aff></affiliation><affiliation><nlm:aff id="A13">Department of Oncology, Odense University Hospital, Odense, Denmark</nlm:aff></affiliation></author><author><name sortKey="Harvey, Vernon J" sort="Harvey, Vernon J" uniqKey="Harvey V" first="Vernon J." last="Harvey">Vernon J. Harvey</name><affiliation><nlm:aff id="A14">Auckland City Hospital, Auckland, New Zealand</nlm:aff></affiliation></author><author><name sortKey="Neven, Patrick" sort="Neven, Patrick" uniqKey="Neven P" first="Patrick" last="Neven">Patrick Neven</name><affiliation><nlm:aff id="A15">Department of Oncology, KU Leuven (University of Leuven), Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Multidisciplinary Breast Center, University Hospitals Leuven, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Treilleux, Isabelle" sort="Treilleux, Isabelle" uniqKey="Treilleux I" first="Isabelle" last="Treilleux">Isabelle Treilleux</name><affiliation><nlm:aff id="A17">Centre Léon Bérard, Lyon, France</nlm:aff></affiliation></author><author><name sortKey="Rasmussen, Birgitte Bruun" sort="Rasmussen, Birgitte Bruun" uniqKey="Rasmussen B" first="Birgitte Bruun" last="Rasmussen">Birgitte Bruun Rasmussen</name><affiliation><nlm:aff id="A18">Herlev Hospital, Herlev, Denmark</nlm:aff></affiliation></author><author><name sortKey="Maibach, Rudolf" sort="Maibach, Rudolf" uniqKey="Maibach R" first="Rudolf" last="Maibach">Rudolf Maibach</name><affiliation><nlm:aff id="A19">IBCSG Coordinating Center, Bern, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Price, Karen N" sort="Price, Karen N" uniqKey="Price K" first="Karen N." last="Price">Karen N. Price</name><affiliation><nlm:aff id="A2">International Breast Cancer Study Group (IBCSG) Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A20">IBCSG Statistical Center, Frontier Science and Technology Research Foundation, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Coates, Alan S" sort="Coates, Alan S" uniqKey="Coates A" first="Alan S." last="Coates">Alan S. Coates</name><affiliation><nlm:aff id="A21">International Breast Cancer Study Group and University of Sydney, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Goldhirsch, Aron" sort="Goldhirsch, Aron" uniqKey="Goldhirsch A" first="Aron" last="Goldhirsch">Aron Goldhirsch</name><affiliation><nlm:aff id="A22">European Institute of Oncology, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Pagani, Olivia" sort="Pagani, Olivia" uniqKey="Pagani O" first="Olivia" last="Pagani">Olivia Pagani</name><affiliation><nlm:aff id="A23">Institute of Oncology of Southern Switzerland (IOSI), Swiss Group for Clinical Cancer Research (SAKK) and IBCSG Ospedale Italiano, Viganello, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Viale, Giuseppe" sort="Viale, Giuseppe" uniqKey="Viale G" first="Giuseppe" last="Viale">Giuseppe Viale</name><affiliation><nlm:aff id="A8">IBCSG Central Pathology Office, Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Rae, James M" sort="Rae, James M" uniqKey="Rae J" first="James M." last="Rae">James M. Rae</name><affiliation><nlm:aff id="A24">University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Regan, Meredith M" sort="Regan, Meredith M" uniqKey="Regan M" first="Meredith M." last="Regan">Meredith M. Regan</name><affiliation><nlm:aff id="A2">International Breast Cancer Study Group (IBCSG) Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A25">Harvard Medical School, Boston, MA, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25935582</idno><idno type="pmc">4763278</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763278</idno><idno type="RBID">PMC:4763278</idno><idno type="doi">10.1007/s10549-015-3378-3</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">002010</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002010</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>CYP19A1</italic> polymorphisms and clinical outcomes in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1–98 trial</title><author><name sortKey="Leyland Jones, Brian" sort="Leyland Jones, Brian" uniqKey="Leyland Jones B" first="Brian" last="Leyland-Jones">Brian Leyland-Jones</name><affiliation><nlm:aff id="A1">Avera Cancer Institute, 1000 E 23rd Street, Sioux Falls, SD 57105, USA</nlm:aff></affiliation></author><author><name sortKey="Gray, Kathryn P" sort="Gray, Kathryn P" uniqKey="Gray K" first="Kathryn P." last="Gray">Kathryn P. Gray</name><affiliation><nlm:aff id="A2">International Breast Cancer Study Group (IBCSG) Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A3">Harvard School of Public Health, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Abramovitz, Mark" sort="Abramovitz, Mark" uniqKey="Abramovitz M" first="Mark" last="Abramovitz">Mark Abramovitz</name><affiliation><nlm:aff id="A4">VM Institute of Research, Montreal, QC, Canada</nlm:aff></affiliation></author><author><name sortKey="Bouzyk, Mark" sort="Bouzyk, Mark" uniqKey="Bouzyk M" first="Mark" last="Bouzyk">Mark Bouzyk</name><affiliation><nlm:aff id="A5">AKESOgen, Inc., Norcross, GA, USA</nlm:aff></affiliation></author><author><name sortKey="Young, Brandon" sort="Young, Brandon" uniqKey="Young B" first="Brandon" last="Young">Brandon Young</name><affiliation><nlm:aff id="A1">Avera Cancer Institute, 1000 E 23rd Street, Sioux Falls, SD 57105, USA</nlm:aff></affiliation></author><author><name sortKey="Long, Bradley" sort="Long, Bradley" uniqKey="Long B" first="Bradley" last="Long">Bradley Long</name><affiliation><nlm:aff id="A6">Genomic Molecular Pathology, Department of Pathology, University of Chicago, Chicago, IL, USA</nlm:aff></affiliation></author><author><name sortKey="Kammler, Roswitha" sort="Kammler, Roswitha" uniqKey="Kammler R" first="Roswitha" last="Kammler">Roswitha Kammler</name><affiliation><nlm:aff id="A7">IBCSG Coordinating Center and Central Pathology Office, Bern, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Dell Orto, Patrizia" sort="Dell Orto, Patrizia" uniqKey="Dell Orto P" first="Patrizia" last="Dell'Orto">Patrizia Dell'Orto</name><affiliation><nlm:aff id="A8">IBCSG Central Pathology Office, Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Biasi, Maria Olivia" sort="Biasi, Maria Olivia" uniqKey="Biasi M" first="Maria Olivia" last="Biasi">Maria Olivia Biasi</name><affiliation><nlm:aff id="A9">Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Thurlimann, Beat" sort="Thurlimann, Beat" uniqKey="Thurlimann B" first="Beat" last="Thürlimann">Beat Thürlimann</name><affiliation><nlm:aff id="A10">Breast Center, Kantonsspital, St. Gallen, Switzerland</nlm:aff></affiliation><affiliation><nlm:aff id="A11">Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Lyng, Maria B" sort="Lyng, Maria B" uniqKey="Lyng M" first="Maria B." last="Lyng">Maria B. Lyng</name><affiliation><nlm:aff id="A12">Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark</nlm:aff></affiliation></author><author><name sortKey="Ditzel, Henrik J" sort="Ditzel, Henrik J" uniqKey="Ditzel H" first="Henrik J." last="Ditzel">Henrik J. Ditzel</name><affiliation><nlm:aff id="A12">Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark</nlm:aff></affiliation><affiliation><nlm:aff id="A13">Department of Oncology, Odense University Hospital, Odense, Denmark</nlm:aff></affiliation></author><author><name sortKey="Harvey, Vernon J" sort="Harvey, Vernon J" uniqKey="Harvey V" first="Vernon J." last="Harvey">Vernon J. Harvey</name><affiliation><nlm:aff id="A14">Auckland City Hospital, Auckland, New Zealand</nlm:aff></affiliation></author><author><name sortKey="Neven, Patrick" sort="Neven, Patrick" uniqKey="Neven P" first="Patrick" last="Neven">Patrick Neven</name><affiliation><nlm:aff id="A15">Department of Oncology, KU Leuven (University of Leuven), Leuven, Belgium</nlm:aff></affiliation><affiliation><nlm:aff id="A16">Multidisciplinary Breast Center, University Hospitals Leuven, Leuven, Belgium</nlm:aff></affiliation></author><author><name sortKey="Treilleux, Isabelle" sort="Treilleux, Isabelle" uniqKey="Treilleux I" first="Isabelle" last="Treilleux">Isabelle Treilleux</name><affiliation><nlm:aff id="A17">Centre Léon Bérard, Lyon, France</nlm:aff></affiliation></author><author><name sortKey="Rasmussen, Birgitte Bruun" sort="Rasmussen, Birgitte Bruun" uniqKey="Rasmussen B" first="Birgitte Bruun" last="Rasmussen">Birgitte Bruun Rasmussen</name><affiliation><nlm:aff id="A18">Herlev Hospital, Herlev, Denmark</nlm:aff></affiliation></author><author><name sortKey="Maibach, Rudolf" sort="Maibach, Rudolf" uniqKey="Maibach R" first="Rudolf" last="Maibach">Rudolf Maibach</name><affiliation><nlm:aff id="A19">IBCSG Coordinating Center, Bern, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Price, Karen N" sort="Price, Karen N" uniqKey="Price K" first="Karen N." last="Price">Karen N. Price</name><affiliation><nlm:aff id="A2">International Breast Cancer Study Group (IBCSG) Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A20">IBCSG Statistical Center, Frontier Science and Technology Research Foundation, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Coates, Alan S" sort="Coates, Alan S" uniqKey="Coates A" first="Alan S." last="Coates">Alan S. Coates</name><affiliation><nlm:aff id="A21">International Breast Cancer Study Group and University of Sydney, Sydney, Australia</nlm:aff></affiliation></author><author><name sortKey="Goldhirsch, Aron" sort="Goldhirsch, Aron" uniqKey="Goldhirsch A" first="Aron" last="Goldhirsch">Aron Goldhirsch</name><affiliation><nlm:aff id="A22">European Institute of Oncology, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Pagani, Olivia" sort="Pagani, Olivia" uniqKey="Pagani O" first="Olivia" last="Pagani">Olivia Pagani</name><affiliation><nlm:aff id="A23">Institute of Oncology of Southern Switzerland (IOSI), Swiss Group for Clinical Cancer Research (SAKK) and IBCSG Ospedale Italiano, Viganello, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Viale, Giuseppe" sort="Viale, Giuseppe" uniqKey="Viale G" first="Giuseppe" last="Viale">Giuseppe Viale</name><affiliation><nlm:aff id="A8">IBCSG Central Pathology Office, Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Rae, James M" sort="Rae, James M" uniqKey="Rae J" first="James M." last="Rae">James M. Rae</name><affiliation><nlm:aff id="A24">University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA</nlm:aff></affiliation></author><author><name sortKey="Regan, Meredith M" sort="Regan, Meredith M" uniqKey="Regan M" first="Meredith M." last="Regan">Meredith M. Regan</name><affiliation><nlm:aff id="A2">International Breast Cancer Study Group (IBCSG) Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A25">Harvard Medical School, Boston, MA, USA</nlm:aff></affiliation></author></analytic><series><title level="j">Breast cancer research and treatment</title><idno type="ISSN">0167-6806</idno><idno type="eISSN">1573-7217</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">To determine whether <italic>CYP19A1</italic> polymorphisms are associated with abnormal activity of aromatase and with musculoskeletal and bone side effects of aromatase inhibitors. DNA was isolated from tumor specimens of 4861 postmenopausal women with hormone receptor-positive breast cancer enrolled in the BIG 1–98 trial to receive tamoxifen and/or letrozole for 5 years. Tumors were genotyped for six <italic>CYP19A1</italic> polymorphisms using PCR-based methods. Associations with breast cancer-free interval (BCFI), distant recurrence-free interval (DRFI), musculoskeletal and bone adverse events (AEs) were assessed using Cox proportional hazards models. All statistical tests were two-sided. No association between the <italic>CYP19A1</italic> genotypes and BCFI or DRFI was observed overall. A reduced risk of a breast cancer event for tamoxifen-treated patients with rs700518 variants was observed (BCFI CC/TC vs. TT: HR 0.53, 95 % CI 0.34–0.82, interaction <italic>P</italic> = 0.08), but not observed for letrozole-treated patients. There was an increased risk of musculoskeletal AEs for patients with rs700518 variants CC/TC versus TT (HR 1.22, 95 % CI 1.03–1.45, <italic>P</italic> = 0.02), regardless of treatment. Tamoxifen-treated patients with rs4646 variants had a reduced risk of bone AEs (AA/CA vs. CC: HR 0.76, 95 % CI 0.59–0.98), whereas an increase of minor allele (C) of rs10046 was associated with an increased risk of bone AEs (HR 1.28, 95 % CI 1.07–1.52). rs936308 variants were associated with a reduced risk of bone AEs in letrozole-treated patients (GG/GC vs. CC: HR 0.73, 95 % CI 0.54–0.99), different from in tamoxifen-treated patients (GG/GC vs. CC: HR 1.32, 95 % CI 0.92–1.90, interaction <italic>P</italic> = 0.01). <italic>CYP19A1</italic> rs700518 variants showed associations with BCFI, DRFI, in tamoxifen treated patients and musculoskeletal AEs regardless of treatment. SNPs rs4646, rs10046, and rs936308 were associated with bone AEs.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
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<front><journal-meta><journal-id journal-id-type="nlm-journal-id">8111104</journal-id><journal-id journal-id-type="pubmed-jr-id">1254</journal-id><journal-id journal-id-type="nlm-ta">Breast Cancer Res Treat</journal-id><journal-id journal-id-type="iso-abbrev">Breast Cancer Res. Treat.</journal-id><journal-title-group><journal-title>Breast cancer research and treatment</journal-title></journal-title-group><issn pub-type="ppub">0167-6806</issn><issn pub-type="epub">1573-7217</issn></journal-meta><article-meta><article-id pub-id-type="pmid">25935582</article-id><article-id pub-id-type="pmc">4763278</article-id><article-id pub-id-type="doi">10.1007/s10549-015-3378-3</article-id><article-id pub-id-type="manuscript">NIHMS731990</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title><italic>CYP19A1</italic> polymorphisms and clinical outcomes in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1–98 trial</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Leyland-Jones</surname><given-names>Brian</given-names></name><email>bleylandj@aol.com</email><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Gray</surname><given-names>Kathryn P.</given-names></name><email>pkruan@jimmy.harvard.edu</email><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Abramovitz</surname><given-names>Mark</given-names></name><email>mark.abramovitz@gmail.com</email><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Bouzyk</surname><given-names>Mark</given-names></name><email>mbouzyk@akesogen.com</email><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Young</surname><given-names>Brandon</given-names></name><email>Brandon.Young@avera.org</email><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Long</surname><given-names>Bradley</given-names></name><email>bradley.long@uchospitals.edu</email><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Kammler</surname><given-names>Roswitha</given-names></name><email>rosita.kammler@ibcsg.org</email><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Dell'Orto</surname><given-names>Patrizia</given-names></name><email>patrizia.dellorto@ieo.it</email><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Biasi</surname><given-names>Maria Olivia</given-names></name><email>olivia.biasi@ieo.it</email><xref ref-type="aff" rid="A9">9</xref></contrib><contrib contrib-type="author"><name><surname>Thürlimann</surname><given-names>Beat</given-names></name><email>beat.thuerlimann@kssg.ch</email><xref ref-type="aff" rid="A10">10</xref><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Lyng</surname><given-names>Maria B.</given-names></name><email>mlyng@health.sdu.dk</email><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Ditzel</surname><given-names>Henrik J.</given-names></name><email>hditzel@health.sdu.dk</email><xref ref-type="aff" rid="A12">12</xref><xref ref-type="aff" rid="A13">13</xref></contrib><contrib contrib-type="author"><name><surname>Harvey</surname><given-names>Vernon J.</given-names></name><email>vernonh@adhb.govt.nz</email><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>Neven</surname><given-names>Patrick</given-names></name><email>patrick.neven@uzleuven.be</email><xref ref-type="aff" rid="A15">15</xref><xref ref-type="aff" rid="A16">16</xref></contrib><contrib contrib-type="author"><name><surname>Treilleux</surname><given-names>Isabelle</given-names></name><email>isabelle.treilleux@lyon.unicancer.fr</email><xref ref-type="aff" rid="A17">17</xref></contrib><contrib contrib-type="author"><name><surname>Rasmussen</surname><given-names>Birgitte Bruun</given-names></name><email>birgitte.bruun.rasmussen@regionh.dk</email><xref ref-type="aff" rid="A18">18</xref></contrib><contrib contrib-type="author"><name><surname>Maibach</surname><given-names>Rudolf</given-names></name><email>rudolf.maibach@ibcsg.org</email><xref ref-type="aff" rid="A19">19</xref></contrib><contrib contrib-type="author"><name><surname>Price</surname><given-names>Karen N.</given-names></name><email>price@jimmy.harvard.edu</email><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A20">20</xref></contrib><contrib contrib-type="author"><name><surname>Coates</surname><given-names>Alan S.</given-names></name><email>alan.coates@ibcsg.org</email><xref ref-type="aff" rid="A21">21</xref></contrib><contrib contrib-type="author"><name><surname>Goldhirsch</surname><given-names>Aron</given-names></name><email>aron.goldhirsch@ibcsg.org</email><xref ref-type="aff" rid="A22">22</xref></contrib><contrib contrib-type="author"><name><surname>Pagani</surname><given-names>Olivia</given-names></name><email>Olivia.pagani@ibcsg.org</email><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Viale</surname><given-names>Giuseppe</given-names></name><email>giuseppe.viale@ieo.it</email><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Rae</surname><given-names>James M.</given-names></name><email>jimmyrae@med.umich.edu</email><xref ref-type="aff" rid="A24">24</xref></contrib><contrib contrib-type="author"><name><surname>Regan</surname><given-names>Meredith M.</given-names></name><email>mregan@jimmy.harvard.edu</email><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A25">25</xref></contrib></contrib-group><aff id="A1"><label>1</label>Avera Cancer Institute, 1000 E 23rd Street, Sioux Falls, SD 57105, USA</aff><aff id="A2"><label>2</label>International Breast Cancer Study Group (IBCSG) Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, USA</aff><aff id="A3"><label>3</label>Harvard School of Public Health, Boston, MA, USA</aff><aff id="A4"><label>4</label>VM Institute of Research, Montreal, QC, Canada</aff><aff id="A5"><label>5</label>AKESOgen, Inc., Norcross, GA, USA</aff><aff id="A6"><label>6</label>Genomic Molecular Pathology, Department of Pathology, University of Chicago, Chicago, IL, USA</aff><aff id="A7"><label>7</label>IBCSG Coordinating Center and Central Pathology Office, Bern, Switzerland</aff><aff id="A8"><label>8</label>IBCSG Central Pathology Office, Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy</aff><aff id="A9"><label>9</label>Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy</aff><aff id="A10"><label>10</label>Breast Center, Kantonsspital, St. Gallen, Switzerland</aff><aff id="A11"><label>11</label>Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland</aff><aff id="A12"><label>12</label>Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark</aff><aff id="A13"><label>13</label>Department of Oncology, Odense University Hospital, Odense, Denmark</aff><aff id="A14"><label>14</label>Auckland City Hospital, Auckland, New Zealand</aff><aff id="A15"><label>15</label>Department of Oncology, KU Leuven (University of Leuven), Leuven, Belgium</aff><aff id="A16"><label>16</label>Multidisciplinary Breast Center, University Hospitals Leuven, Leuven, Belgium</aff><aff id="A17"><label>17</label>Centre Léon Bérard, Lyon, France</aff><aff id="A18"><label>18</label>Herlev Hospital, Herlev, Denmark</aff><aff id="A19"><label>19</label>IBCSG Coordinating Center, Bern, Switzerland</aff><aff id="A20"><label>20</label>IBCSG Statistical Center, Frontier Science and Technology Research Foundation, Boston, MA, USA</aff><aff id="A21"><label>21</label>International Breast Cancer Study Group and University of Sydney, Sydney, Australia</aff><aff id="A22"><label>22</label>European Institute of Oncology, Milan, Italy</aff><aff id="A23"><label>23</label>Institute of Oncology of Southern Switzerland (IOSI), Swiss Group for Clinical Cancer Research (SAKK) and IBCSG Ospedale Italiano, Viganello, Switzerland</aff><aff id="A24"><label>24</label>University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA</aff><aff id="A25"><label>25</label>Harvard Medical School, Boston, MA, USA</aff><pub-date pub-type="nihms-submitted"><day>17</day><month>2</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>03</day><month>5</month><year>2015</year></pub-date><pub-date pub-type="ppub"><month>6</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>6</month><year>2016</year></pub-date><volume>151</volume><issue>2</issue><fpage>373</fpage><lpage>384</lpage><pmc-comment>elocation-id from pubmed: 10.1007/s10549-015-3378-3</pmc-comment>
<abstract><p id="P1">To determine whether <italic>CYP19A1</italic> polymorphisms are associated with abnormal activity of aromatase and with musculoskeletal and bone side effects of aromatase inhibitors. DNA was isolated from tumor specimens of 4861 postmenopausal women with hormone receptor-positive breast cancer enrolled in the BIG 1–98 trial to receive tamoxifen and/or letrozole for 5 years. Tumors were genotyped for six <italic>CYP19A1</italic> polymorphisms using PCR-based methods. Associations with breast cancer-free interval (BCFI), distant recurrence-free interval (DRFI), musculoskeletal and bone adverse events (AEs) were assessed using Cox proportional hazards models. All statistical tests were two-sided. No association between the <italic>CYP19A1</italic> genotypes and BCFI or DRFI was observed overall. A reduced risk of a breast cancer event for tamoxifen-treated patients with rs700518 variants was observed (BCFI CC/TC vs. TT: HR 0.53, 95 % CI 0.34–0.82, interaction <italic>P</italic> = 0.08), but not observed for letrozole-treated patients. There was an increased risk of musculoskeletal AEs for patients with rs700518 variants CC/TC versus TT (HR 1.22, 95 % CI 1.03–1.45, <italic>P</italic> = 0.02), regardless of treatment. Tamoxifen-treated patients with rs4646 variants had a reduced risk of bone AEs (AA/CA vs. CC: HR 0.76, 95 % CI 0.59–0.98), whereas an increase of minor allele (C) of rs10046 was associated with an increased risk of bone AEs (HR 1.28, 95 % CI 1.07–1.52). rs936308 variants were associated with a reduced risk of bone AEs in letrozole-treated patients (GG/GC vs. CC: HR 0.73, 95 % CI 0.54–0.99), different from in tamoxifen-treated patients (GG/GC vs. CC: HR 1.32, 95 % CI 0.92–1.90, interaction <italic>P</italic> = 0.01). <italic>CYP19A1</italic> rs700518 variants showed associations with BCFI, DRFI, in tamoxifen treated patients and musculoskeletal AEs regardless of treatment. SNPs rs4646, rs10046, and rs936308 were associated with bone AEs.</p></abstract><kwd-group><kwd><italic>CYP19A1</italic></kwd><kwd>Aromatase inhibitor</kwd><kwd>Musculoskeletal side effects</kwd><kwd>Bone side effects</kwd><kwd>Letrozole</kwd><kwd>Tamoxifen</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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