Contralateral breast cancers: Independent cancers or metastases?
Contralateral breast cancers: Independent cancers or metastases?
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DOI：
10.1002/ijc.31051
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发表时间：
2018-01-15
影响因子：
6.4
通讯作者：
Reis-Filho JS
中科院分区：
文献类型：
--
作者：
Begg CB;Ostrovnaya I;Geyer FC;Papanastasiou AD;Ng CKY;Sakr RA;Bernstein JL;Burke KA;King TA;Piscuoglio S;Mauguen A;Orlow I;Weigelt B;Seshan VE;Morrow M;Reis-Filho JS
患有先前或同步乳腺癌的女性的对侧乳癌通常被认为是独立的原发肿瘤。新出现的证据表明，在这些病例中的一小部分，第二个肿瘤代表转移。我们试图通过大规模平行测序来研究这个问题，目标是在乳腺癌中反复突变的254个基因。我们检查了纪念斯隆-凯特琳癌症中心1995-2006年期间的肿瘤档案，以确定在该中心进行了两种肿瘤手术的对侧乳腺癌病例。我们报告了通过定向大规模平行测序分析成功分析的49名患者的结果。体细胞突变和拷贝数改变是由最先进的算法定义的。克隆亲缘关系通过专门为此目的设计的统计检验进行评估。我们发现有证据表明，在体细胞突变罕见的密码子匹配突变的基础上，3例(6%)对侧乳房的肿瘤是克隆性相关的。所有3例患者的临床资料和相似的基因拷贝数改变模式均与转移相一致。在另外3例病例中，共同的PIK3CA基因座有一个单独的匹配突变。结果表明，对侧乳腺癌的一部分代表转移，而不是独立的原发肿瘤。大规模平行测序分析可以为明确诊断提供重要证据。然而，考虑到乳腺癌的肿瘤间突变异质性，在所有情况下都需要使用足够大的基因面板来令人信服地定义克隆性。
A cancer in the contralateral breast in a woman with a previous or synchronous breast cancer is typically considered to be an independent primary tumor. Emerging evidence suggests that in a small subset of these cases the second tumor represents a metastasis. We sought to investigate the issue using massively parallel sequencing targeting 254 genes recurrently mutated in breast cancer. We examined the tumor archives at Memorial Sloan Kettering Cancer Center for the period 1995–2006 to identify cases of contralateral breast cancer where surgery for both tumors was performed at the Center. We report results from 49 patients successfully analyzed by a targeted massively parallel sequencing assay. Somatic mutations and copy number alterations were defined by state-of-the-art algorithms. Clonal relatedness was evaluated by statistical tests specifically designed for this purpose. We found evidence that the tumors in contralateral breasts were clonally related in 3 cases (6%) on the basis of matching mutations at codons where somatic mutations are rare. Clinical data and the presence of similar patterns of gene copy number alterations were consistent with metastasis for all 3 cases. In 3 additional cases there was a solitary matching mutation at a common PIK3CA locus. The results suggest that a subset of contralateral breast cancers represent metastases rather than independent primary tumors. Massively parallel sequencing analysis can provide important evidence to clarify the diagnosis. However, given the inter-tumor mutational heterogeneity in breast cancer, sufficiently large gene panels need to be employed to define clonality convincingly in all cases.
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影响因子：
8.8
作者：
Masuda, S.;Kadowaki, T.;Kumaki, N.;Tang, X.;Tokuda, Y.;Yoshimura, S.;Takekoshi, S.;Osamura, R. Y.
通讯作者：
Osamura, R. Y.
DOI：
10.1186/s13058-016-0727-z
发表时间：
2016-06-23
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Begg CB;Ostrovnaya I;Carniello JV;Sakr RA;Giri D;Towers R;Schizas M;De Brot M;Andrade VP;Mauguen A;Seshan VE;King TA
通讯作者：
King TA
影响因子：
8.8
作者：
Kuo, W-H;Yen, A. M-F;Lee, P-H;Chen, K-M;Wang, J.;Chang, K-J;Chen, T. H-H;Tsau, H-S
通讯作者：
Tsau, H-S
影响因子：
3.8
作者：
Klevebring, Daniel;Lindberg, Johan;Czene, Kamila
通讯作者：
Czene, Kamila
影响因子：
3.8
作者：
Janschek, E;Kandioler-Eckersberger, D;Jakesz, R
通讯作者：
Jakesz, R