BRCA1 and BRCA2:: chemosensitivity, treatment outcomes and prognosis
BRCA1 and BRCA2:: chemosensitivity, treatment outcomes and prognosis
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DOI：
10.1007/s10689-005-2832-5
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发表时间：
2006-01-01
期刊：
影响因子：
2.2
通讯作者：
Foulkes, William D.
中科院分区：
文献类型：
--
作者：
Foulkes, William D.
BRCA1和BRCA2是重要的乳腺癌和卵巢癌易感基因，这两个基因的突变使乳腺癌的终生风险高达80%，卵巢癌的终生风险高达40%。临床病理研究已经确定了brca1相关乳腺癌的特异性特征，但这对于brca2相关乳腺癌来说更加困难。由于BRCA1或BRCA2突变引起的卵巢癌通常不能从形态学上与非遗传性卵巢癌区分开来，但微阵列数据表明差异确实存在。预后研究表明，BRCA1突变携带者的乳腺癌预后可能与相同年龄的BRCA2或非BRCA2携带者相似，甚至更糟。相比之下，大多数研究表明，与非携带者相比，患有brca1 /2相关卵巢癌的女性生存率更高，特别是如果她们接受了基于铂的治疗。为了支持这一观点，体外化学敏感性研究发现，缺乏BRCA1的人类细胞可能对顺铂和其他导致DNA双链断裂的药物特别敏感。然而，在乳腺癌中，BRCA1/2突变携带者与非携带者之间，以及现有BRCA1/2突变携带者系列中不同化疗方案之间对化疗反应的临床重要差异知之甚少。没有发表的前瞻性研究。希望在不久的将来，随机对照试验将开始，目的是回答这些重要的临床问题。
BRCA1 and BRCA2 are important breast and ovarian cancer susceptibility genes, and mutations in these two genes confer lifetime risks of breast cancer of up to 80% and ovarian cancer risks of up to 40%. Clinico-pathological studies have identified features that are specific to BRCA1-related breast cancer, but this has been more difficult for BRCA2-related breast cancer. Ovarian cancers due to BRCA1 or BRCA2 mutations cannot usually be distinguished from their non-hereditary counterparts on morphological grounds, but micro-array data suggest that differences do exist. Prognostic studies have shown that breast cancer in a BRCA1 mutation carrier is likely to have a similar, or worse, outcome than that occurring in a BRCA2- or non-carrier of the same age. By contrast, most studies indicate that women developing a BRCA1/2-related ovarian cancer have an improved survival compared with non-carriers, particularly if they receive platinum-based therapy. In support of this, in vitro chemo-sensitivity studies have found that human cells lacking BRCA1 may be particularly sensitive to cisplatinum and to other drugs that cause double-strand breaks in DNA. Nevertheless, in breast cancer, little is known regarding clinically important differences in response to chemotherapy between BRCA1/2 mutation carriers and non-carriers, and between different chemotherapeutic regimens within existing series of BRCA1/2 mutation carriers. There are no published prospective studies. It is hoped that, in the near future, randomised controlled trials will be started with the aim of answering these important clinical questions.