Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).
Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).
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BRCA1和BRCA2突变载体中乳腺癌和卵巢癌的病理学：BRCA1/2修饰符研究者联盟的结果（CIMBA）。
DOI：
10.1158/1055-9965.epi-11-0775
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发表时间：
2012-01
期刊：
影响因子：
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通讯作者：
Consortium of Investigators of Modifiers of BRCA1/2
中科院分区：
文献类型：
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作者：
Mavaddat N;Barrowdale D;Andrulis IL;Domchek SM;Eccles D;Nevanlinna H;Ramus SJ;Spurdle A;Robson M;Sherman M;Mulligan AM;Couch FJ;Engel C;McGuffog L;Healey S;Sinilnikova OM;Southey MC;Terry MB;Goldgar D;O'Malley F;John EM;Janavicius R;Tihomirova L;Hansen TV;Nielsen FC;Osorio A;Stavropoulou A;Benítez J;Manoukian S;Peissel B;Barile M;Volorio S;Pasini B;Dolcetti R;Putignano AL;Ottini L;Radice P;Hamann U;Rashid MU;Hogervorst FB;Kriege M;van der Luijt RB;HEBON;Peock S;Frost D;Evans DG;Brewer C;Walker L;Rogers MT;Side LE;Houghton C;EMBRACE;Weaver J;Godwin AK;Schmutzler RK;Wappenschmidt B;Meindl A;Kast K;Arnold N;Niederacher D;Sutter C;Deissler H;Gadzicki D;Preisler-Adams S;Varon-Mateeva R;Schönbuchner I;Gevensleben H;Stoppa-Lyonnet D;Belotti M;Barjhoux L;GEMO Study Collaborators;Isaacs C;Peshkin BN;Caldes T;de la Hoya M;Cañadas C;Heikkinen T;Heikkilä P;Aittomäki K;Blanco I;Lazaro C;Brunet J;Agnarsson BA;Arason A;Barkardottir RB;Dumont M;Simard J;Montagna M;Agata S;D'Andrea E;Yan M;Fox S;kConFab Investigators;Rebbeck TR;Rubinstein W;Tung N;Garber JE;Wang X;Fredericksen Z;Pankratz VS;Lindor NM;Szabo C;Offit K;Sakr R;Gaudet MM;Singer CF;Tea MK;Rappaport C;Mai PL;Greene MH;Sokolenko A;Imyanitov E;Toland AE;Senter L;Sweet K;Thomassen M;Gerdes AM;Kruse T;Caligo M;Aretini P;Rantala J;von Wachenfeld A;Henriksson K;SWE-BRCA Collaborators;Steele L;Neuhausen SL;Nussbaum R;Beattie M;Odunsi K;Sucheston L;Gayther SA;Nathanson K;Gross J;Walsh C;Karlan B;Chenevix-Trench G;Easton DF;Antoniou AC;Consortium of Investigators of Modifiers of BRCA1/2
此前的小型研究发现，BRCA1 和 BRCA2 乳腺肿瘤的病理学有所不同。对更大的突变携带者数据集的分析应该可以进一步表征肿瘤。我们使用 4,325 名 BRCA1 和 2,568 名 BRCA2 突变携带者的数据来分析浸润性乳腺癌、卵巢癌和对侧乳腺癌的病理学。有强有力的证据表明，BRCA1 携带者中雌激素受体 (ER) 阴性乳腺肿瘤的比例随着诊断时年龄的增加而下降 (p-趋势=1.2×10−5)，但 BRCA2 携带者中雌激素受体 (ER) 阴性乳腺肿瘤的比例随着诊断时年龄的增加而增加 (p-趋势=6.8×10−6)。 BRCA1 携带者的三阴性肿瘤比例随着诊断时的年龄而下降，但 BRCA2 携带者的三阴性肿瘤的比例随着诊断时的年龄而增加。在 BRCA1 和 BRCA2 携带者中，ER 阴性肿瘤的组织学分级高于 ER 阳性肿瘤（3 级与 1 级，BRCA1 的 p=1.2×10−13，BRCA2 的 p=0.001）。 ER和孕激素受体（PR）表达与突变携带者状态独立相关（联合分析中，BRCA2的ER阳性比值比（OR）=9.4，95%CI：7.0-12.6，PR阳性OR=1.7，95%CI：1.3-2.3）。小叶肿瘤更有可能与 BRCA2 相关（BRCA2 的 OR=3.3，95%CI：2.4-4.4，p=4.4×10−14），髓样肿瘤更可能与 BRCA1 相关（BRCA2 的 OR=0.25，95%CI：0.18-0.35，p=2.3×10−15）。第一个乳腺癌的 ER 状态可以预测异步对侧乳腺癌的 ER 状态（对于 BRCA1，p=0.0004；对于 BRCA2，p=0.002）。 BRCA1 和 BRCA2 携带者之间的卵巢癌形态无显着差异（浆液性：67%；粘液性：1%；子宫内膜样：12%；透明细胞：2%）。 BRCA1 和 BRCA2 肿瘤的病理学特征可能有助于改进风险预测算法并为筛查和预防的临床策略提供信息。
Previous small studies found that BRCA1 and BRCA2 breast tumors differ in their pathology. Analysis of larger datasets of mutation carriers should allow further tumor characterization. We used data from 4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of invasive breast, ovarian and contralateral breast cancers. There was strong evidence that the proportion of estrogen receptor (ER)-negative breast tumors decreased with age at diagnosis among BRCA1 (p-trend=1.2×10−5) but increased with age at diagnosis among BRCA2 carriers (p-trend=6.8×10−6). The proportion of triple negative tumors decreased with age at diagnosis in BRCA1 carriers but increased with age at diagnosis of BRCA2 carriers. In both BRCA1 and BRCA2 carriers, ER-negative tumors were of higher histological grade than ER-positive tumors (Grade 3 vs. Grade 1, p=1.2×10−13 for BRCA1 and p=0.001 for BRCA2). ER and progesterone receptor (PR) expression were independently associated with mutation carrier status (ER-positive odds ratio (OR) for BRCA2=9.4, 95%CI:7.0-12.6 and PR-positive OR=1.7, 95%CI:1.3-2.3, under joint analysis). Lobular tumors were more likely to be BRCA2-related (OR for BRCA2=3.3, 95%CI:2.4-4.4, p=4.4×10−14), and medullary tumors BRCA1-related (OR for BRCA2=0.25, 95%CI:0.18-0.35, p=2.3×10−15). ER-status of the first breast cancer was predictive of ER-status of asynchronous contralateral breast cancer (p=0.0004 for BRCA1; p=0.002 for BRCA2). There were no significant differences in ovarian cancer morphology between BRCA1 and BRCA2 carriers (serous:67%; mucinous:1%; endometriod:12%; clear-cell:2%). Pathology characteristics of BRCA1 and BRCA2 tumors may be useful for improving risk prediction algorithms and informing clinical strategies for screening and prophylaxis.