Response to neo-adjuvant chemotherapy in women with BRCA1-positive breast cancers
Response to neo-adjuvant chemotherapy in women with BRCA1-positive breast cancers
复制标题
DOI：
10.1007/s10549-007-9600-1
复制
发表时间：
2008-03-01
影响因子：
3.8
通讯作者：
Lubinski, J.
中科院分区：
文献类型：
--
作者：
Byrski, T.;Gronwald, J.;Lubinski, J.
目的 迄今为止，尚无研究探讨不同化疗方案对携带 BRCA1 种系突变的乳腺癌女性的相对有效性。我们希望比较 BRCA1 突变携带者和非携带者对照对新辅助化疗的反应率。实验设计从 3,479 名患者的登记中，我们确定了 44 名携带 BRCA1 创始人突变并接受过乳腺癌新辅助化疗治疗的波兰女性，以及 41 名年龄和医院匹配的对照。结果 44 名 BRCA1 突变携带者中有 35 名 (80%) 经历了部分或完全缓解新辅助化疗，与 41 名非携带者中的 39 名 (95%) 相比 (P = 0.05)。在遗传性亚组中，反应率根据是否给予紫杉烷（多西紫杉醇）而有所不同。 15 名 BRCA1 携带者女性中，有 6 名接受多西紫杉醇联合多柔比星治疗有反应（完全或部分），而 29 名接受其他（DNA 损伤）治疗的女性中有 29 名出现反应（P = 0.001）。在非携带者中，对两类化疗的反应率相似。 结论 BRCA1 携带者中的乳腺癌在新辅助治疗中通常不表现出对多西他赛的敏感性。有丝分裂纺锤体毒物的临床反应可能需要正常的 BRCA1。
Purpose There have been no studies to date which look at the relative effectiveness of different regimens of chemotherapy in women who have breast cancer and who carry a BRCA1 germ-line mutation. We wished to compare rates of response to neo-adjuvant chemotherapy in BRCA1 mutation carriers and non-carrier controls.Experimental design From a registry of 3,479 patients, we identified 44 Polish women who carried a BRCA1 founder mutation and who had been treated with neo-adjuvant chemotherapy for breast cancer, and 41 age- and hospital-matched controls.Results 35 of the 44 BRCA1 mutation carriers (80%) experienced a partial or complete response to neo-adjuvant chemotherapy, compared to 39 of the 41 (95%) non-carriers (P = 0.05). In the hereditary subgroup, response rates differed depending on whether or not a taxane (docetaxel) was given. Six of the 15 BRCA1 carrier women given docetaxel with doxorubicin responded (complete or partial), compared to 29 of 29 given other (DNA-damaging) therapies (P = 0.001). Among the non-carriers, the rates of response to the two categories of chemotherapy were similar.Conclusions Breast cancers among BRCA1 carriers frequently do not exhibit sensitivity to docetaxel in the neo-adjuvant setting. It is likely that normal BRCA1 is required for clinical response to mitotic spindle poisons.