Molecular clonality determination of ipsilateral recurrence of invasive breast carcinomas after breast-conserving therapy - Comparison with clinical and biologic factors

Molecular clonality determination of ipsilateral recurrence of invasive breast carcinomas after breast-conserving therapy - Comparison with clinical and biologic factors
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DOI:
10.1309/dp47pk9pvc52au4r
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发表时间:
2005-05-01
影响因子:
3.5
通讯作者:
Kestin, LL
Kestin, LL
中科院分区:
医学4区
文献类型:
--
作者:
Goldstein, NS;Vicini, FA;Kestin, LL

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我们使用分子聚合酶链反应杂合性丢失(洛)分析法,对26例在IBF洛为+/- 50%等位基因丢失之前接受保乳治疗的浸润性癌患者进行了研究,以建立浸润性同侧乳腺衰竭(IBF;局部复发)与初始浸润性癌之间的克隆性关系。18例IBF(69%)与初始癌克隆相关; 8例(31%)克隆不同,第二原发癌。IBFs和初始浸润癌的形态相似,在6(75%)8克隆不同的情况下。11例(42%)患者的临床IBF、11个分型的FRED和分子检测结果不一致。相关病例至IBF的平均间隔为4.7年,不同病例为8.7年(P = 0.013)。6例患者发生DM; 5例发生相关IBF。在相关的IBF病例中,与DM相关的IBF的等位基因丢失分数(FAL)平均增加18.9%,而与DM无关的病例为7.6%(P = 0.004)。分子检测可以准确地确定大多数IBF的克隆性。形态学比较和临床IBF分型是不可靠的方法来确定克隆。克隆相关的IBF发生早于克隆不同的IBF。克隆相关IBF患者是发生DM的主要人群。并非所有克隆相关IBF均与DM相关; FAL增加较大的患者与DM相关。分子克隆性检测可能提供一种可靠的方法来识别IBF时可能从全身化疗中获益的患者。
We established clonality relationships between invasive ipsilateral breast failures (IBFs; local recurrences) and initial invasive carcinomas using a molecular polymerase chain reaction loss of heterozygosity (LOH) assay for 26 patients treated with breast-conserving therapy for invasive carcinoma with no distant metastases (DMs) before the IBF LOH was +/- 50% allelic loss. Eighteen IBFs (69%) were related clonally to initial carcinomas; 8 (31%) were clonally distinct, second primary carcinomas. IBFs and initial invasive carcinomas were morphologically similar in 6 (75%) of 8 clonally different cases. Clinical IBF,ftred in 11 classification and molecular assay results differed in 11 cases (42%). The mean intervals to IBF were 4.7 years in related and 8.7 years in different cases (P =.013). In 6 patients, DMs developed; 5 had related IBFs. In related IBF cases, the mean increase in fractional allelic loss (FAL) of IBFs associated with DMs was 18.9% compared with 7.6% in cases unassociated with DMs (P =.004). Molecular assays can accurately establish the clonality of most IBFs. Morphologic comparison and clinical IBF classification are unreliable methods of determining clonaliry. Clonally related IBFs occurred sooner than clonally different IBFs. Patients with clonally related IBFs are the main pool in which DMs occur Not all clonally related IBFs have the same DM association; those with large FAL gains were associated with DMs. Molecular clonality assays may provide a reliable means of identifying patients who might benefit from systemic chemotherapy at the time of IBF.