ESR1基因突变与乳腺癌内分泌治疗耐药的相关性
发布时间：2018-08-22 10:32
【摘要】：目的:比较氟维司群500mg与依西美坦25mg 一线治疗雌激素受体阳性晚期乳腺癌患者的疗效、安全性,并探索性分析依西美坦和氟维司群治疗ESR1基因突变患者的疗效,以及ESR1突变与芳香化酶抑制剂获得性耐药的关系。方法:评价中国医学科学院肿瘤医院2016年入组氟维司群(500mg)对比依西美坦一线治疗经辅助非甾体类芳香化酶抑制剂治疗的绝经后雌激素受体阳性、HER2阴性晚期乳腺癌的随机、开放、多中心临床研究的患者治疗疗效和安全性,并在治疗的不同阶段采集血样,用二代测序方法检测ESR1突变,得到各患者ESR1突变信息,分析ESR1突变与芳香化酶抑制剂获得性耐药的关系。结果:1、疗效评价:入组患者中可用于疗效评价的共12例:依西美坦组5例(4例PD,1例SD),氟维司群组7例(2例PD,3例SD,2例PR)。两组的疗效相关指标比较如下:依西美坦组平均PFS 2.8月,客观缓解率(ORR)0,疾病控制率(DCR)20%,平均至治疗失败时间(TTF)2.9月;氟维司群组平均PFS 4.0月,ORR 28.6%,DCR 71.4%,平均TTF 2.8月。2、安全性评价:截止2017年3月10日,入组的18例患者中尚无不良事件记录。依西美坦组常见潮热、关节痛等,氟维司群组常见注射部位反应等,均为轻度,未达不良事件评价标准。3、ESR1基因突变与疗效的关系:上述患者中有3例可检测到ESR1突变,结合相应的用药和疗效依次为E380Q(依西美坦组,PD,PFS2.8月)、D540G(氟维司群组,PD,PFS2.8月)和D538G(氟维司群组,SD,PFS2.6月)。4、突变基因治疗前后的丰度变化:本研究检出的基因突变丰度较治疗前升高的患者有4例(3例PD,1例SD),突变丰度较治疗前下降的患者有1例(SD),部分突变丰度升高、部分突变丰度下降的患者有1例(SD)。结论:1、上述结果表明氟维司群(500mg)组的疗效优于依西美坦组。2、两种内分泌治疗方案的安全性均较好,在患者耐受范围内。3、本研究结果暂无法证明ESR1基因突变与内分泌治疗耐药之间的关系。4、治疗过程中,某些致病基因突变丰度升高,可能提示疗效不佳;反之,致病基因突变丰度下降,可能提示治疗有效。
[Abstract]:Objective: to compare the efficacy and safety of 500mg and 25mg in the treatment of estrogen receptor positive patients with advanced breast cancer. And the relationship between ESR1 mutation and acquired resistance of aromatase inhibitors. Methods: to evaluate the randomness and openness of first-line treatment of postmenopausal estrogen receptor positive and HER2 negative advanced breast cancer treated with adjuvant nonsteroidal aromatase inhibitor (NSAID) by 500mg in 2016 from Cancer Hospital of Chinese Academy of Medical Sciences. The efficacy and safety of multi-center clinical study were analyzed. Blood samples were collected at different stages of treatment, and ESR1 mutation was detected by second-generation sequencing method. The information of ESR1 mutation was obtained. To analyze the relationship between ESR1 mutation and acquired drug resistance of aromatase inhibitors. Results: 12 patients were included in the group: 5 patients in the Ecilimetin group (4 patients with SD),) and 7 patients with SD), fluvix group (2 patients with PDN 3 patients with SD2 with PR). The results of the two groups were compared as follows: the average PFS of the two groups was 2.8 months, the objective remission rate was 0, the disease control rate was 20, and the average time of failure was (TTF) 2.9 months. The average PFS of fluvix group was 28.60.0.The average TTF was 2.8 months. 2. 2. Safety evaluation: as of March 10, 2017, there was no adverse event record in 18 patients. The common hot flashes, joint pain and common injection site reactions of fluvix group were mild, and the relationship between the mutation of ESR1 gene and the efficacy of ESR1 gene was not up to the standard of adverse event evaluation. Three of the above patients could detect ESR1 mutation. Combined with the corresponding drug use and efficacy, E380Q (E380Q (E380Q) (E380Q) (E380Q) (E380Q) (E380Q) D540G (PFS2.8 months) and D538G (PFS2.6 months), the mutation gene abundance changes before and after treatment: the mutation abundance detected in this study is higher than that detected before and after treatment. The mutation abundance of SD), was increased in 4 patients (3 patients with SD), mutation decreased in 1 patient compared with those before treatment). The partial mutation abundance of (SD), was increased in 1 patient. One patient with reduced partial mutation abundance had (SD). Conclusion: 1, the above results show that the efficacy of 500mg group is better than that of Ixemetam group .2.The safety of the two endocrine therapies is better. In the range of patient tolerance. 3, the results of this study can not prove the relationship between the mutation of ESR1 gene and the resistance of endocrine therapy. The increase of mutation abundance of some pathogenic genes in the course of treatment may indicate that the curative effect is not good. The decrease in mutation abundance of pathogenic genes may suggest that treatment is effective.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.9
本文编号：2196833
[Abstract]:Objective: to compare the efficacy and safety of 500mg and 25mg in the treatment of estrogen receptor positive patients with advanced breast cancer. And the relationship between ESR1 mutation and acquired resistance of aromatase inhibitors. Methods: to evaluate the randomness and openness of first-line treatment of postmenopausal estrogen receptor positive and HER2 negative advanced breast cancer treated with adjuvant nonsteroidal aromatase inhibitor (NSAID) by 500mg in 2016 from Cancer Hospital of Chinese Academy of Medical Sciences. The efficacy and safety of multi-center clinical study were analyzed. Blood samples were collected at different stages of treatment, and ESR1 mutation was detected by second-generation sequencing method. The information of ESR1 mutation was obtained. To analyze the relationship between ESR1 mutation and acquired drug resistance of aromatase inhibitors. Results: 12 patients were included in the group: 5 patients in the Ecilimetin group (4 patients with SD),) and 7 patients with SD), fluvix group (2 patients with PDN 3 patients with SD2 with PR). The results of the two groups were compared as follows: the average PFS of the two groups was 2.8 months, the objective remission rate was 0, the disease control rate was 20, and the average time of failure was (TTF) 2.9 months. The average PFS of fluvix group was 28.60.0.The average TTF was 2.8 months. 2. 2. Safety evaluation: as of March 10, 2017, there was no adverse event record in 18 patients. The common hot flashes, joint pain and common injection site reactions of fluvix group were mild, and the relationship between the mutation of ESR1 gene and the efficacy of ESR1 gene was not up to the standard of adverse event evaluation. Three of the above patients could detect ESR1 mutation. Combined with the corresponding drug use and efficacy, E380Q (E380Q (E380Q) (E380Q) (E380Q) (E380Q) (E380Q) D540G (PFS2.8 months) and D538G (PFS2.6 months), the mutation gene abundance changes before and after treatment: the mutation abundance detected in this study is higher than that detected before and after treatment. The mutation abundance of SD), was increased in 4 patients (3 patients with SD), mutation decreased in 1 patient compared with those before treatment). The partial mutation abundance of (SD), was increased in 1 patient. One patient with reduced partial mutation abundance had (SD). Conclusion: 1, the above results show that the efficacy of 500mg group is better than that of Ixemetam group .2.The safety of the two endocrine therapies is better. In the range of patient tolerance. 3, the results of this study can not prove the relationship between the mutation of ESR1 gene and the resistance of endocrine therapy. The increase of mutation abundance of some pathogenic genes in the course of treatment may indicate that the curative effect is not good. The decrease in mutation abundance of pathogenic genes may suggest that treatment is effective.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.9
【参考文献】
相关期刊论文 前4条
1 Meng Zhao;Bhuvaneswari Ramaswamy;;Mechanisms and therapeutic advances in the management of endocrine-resistant breast cancer[J];World Journal of Clinical Oncology;2014年03期
2 王佳玉;徐兵河;;2014年美国临床肿瘤学会年会报道:乳腺癌内科治疗最新进展[J];中华乳腺病杂志(电子版);2014年04期
3 徐兵河;;2013年最重要的乳腺癌研究进展[J];中华乳腺病杂志(电子版);2014年01期
4 李力,钟艳萍,张玮,张洁清,姚忠强;C-erbB2、C-erbB3、C-erbB4的表达与卵巢恶性肿瘤的关系[J];癌症;2004年05期
，本文编号：2196833
本文链接：https://www.wllwen.com/yixuelunwen/zlx/2196833.html
