ESR1基因突變與乳腺癌內(nèi)分泌治療耐藥的相關(guān)性
發(fā)布時間：2018-08-22 10:32
【摘要】：目的:比較氟維司群500mg與依西美坦25mg 一線治療雌激素受體陽性晚期乳腺癌患者的療效、安全性,并探索性分析依西美坦和氟維司群治療ESR1基因突變患者的療效,以及ESR1突變與芳香化酶抑制劑獲得性耐藥的關(guān)系。方法:評價中國醫(yī)學(xué)科學(xué)院腫瘤醫(yī)院2016年入組氟維司群(500mg)對比依西美坦一線治療經(jīng)輔助非甾體類芳香化酶抑制劑治療的絕經(jīng)后雌激素受體陽性、HER2陰性晚期乳腺癌的隨機、開放、多中心臨床研究的患者治療療效和安全性,并在治療的不同階段采集血樣,用二代測序方法檢測ESR1突變,得到各患者ESR1突變信息,分析ESR1突變與芳香化酶抑制劑獲得性耐藥的關(guān)系。結(jié)果:1、療效評價:入組患者中可用于療效評價的共12例:依西美坦組5例(4例PD,1例SD),氟維司群組7例(2例PD,3例SD,2例PR)。兩組的療效相關(guān)指標(biāo)比較如下:依西美坦組平均PFS 2.8月,客觀緩解率(ORR)0,疾病控制率(DCR)20%,平均至治療失敗時間(TTF)2.9月;氟維司群組平均PFS 4.0月,ORR 28.6%,DCR 71.4%,平均TTF 2.8月。2、安全性評價:截止2017年3月10日,入組的18例患者中尚無不良事件記錄。依西美坦組常見潮熱、關(guān)節(jié)痛等,氟維司群組常見注射部位反應(yīng)等,均為輕度,未達不良事件評價標(biāo)準(zhǔn)。3、ESR1基因突變與療效的關(guān)系:上述患者中有3例可檢測到ESR1突變,結(jié)合相應(yīng)的用藥和療效依次為E380Q(依西美坦組,PD,PFS2.8月)、D540G(氟維司群組,PD,PFS2.8月)和D538G(氟維司群組,SD,PFS2.6月)。4、突變基因治療前后的豐度變化:本研究檢出的基因突變豐度較治療前升高的患者有4例(3例PD,1例SD),突變豐度較治療前下降的患者有1例(SD),部分突變豐度升高、部分突變豐度下降的患者有1例(SD)。結(jié)論:1、上述結(jié)果表明氟維司群(500mg)組的療效優(yōu)于依西美坦組。2、兩種內(nèi)分泌治療方案的安全性均較好,在患者耐受范圍內(nèi)。3、本研究結(jié)果暫無法證明ESR1基因突變與內(nèi)分泌治療耐藥之間的關(guān)系。4、治療過程中,某些致病基因突變豐度升高,可能提示療效不佳;反之,致病基因突變豐度下降,可能提示治療有效。
[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.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.9
本文編號：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.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.9
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相關(guān)期刊論文 前4條
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