雌激素解救晚期内分泌治疗耐药乳腺癌的临床观察

A clinical study of estradiol therapy in endocrine - resistant advanced breast cancer

目的在晚期三线内分泌治疗耐药乳腺癌患者中，明确循环肿瘤细胞（CTCs）中FAS表达与雌激素疗效的关系，并研究雌激素在逆转内分泌治疗耐药时所起的作用。方法20例检测到外周血中CTCs且其上FAS表达呈阳性的晚期三线内分泌治疗耐药乳腺癌患者应用雌二醇片剂2mg口服，每日3次，4周为一周期。当雌二醇治疗临床获益的患者再次出现疾病进展时，给予阿那曲唑1mg口服，每日1次，4周为一周期。每周期重复影像学检查和CTCs检测，并评价疗效。结果20例患者中失访1例，可供评价19例。应用雌二醇后，由实体瘤RECISTl．0标准判断疗效：CR0例，PR2例（10．5％），SD5例（26．3％），PD12例（63．2％），客观缓解率10．5％，临床获益率36．8％。中位无进展生存期6．0个月。由CTCs标准判断疗效：CR0例，PR2例（10．5％），SD4例（21．1％），PD13例（68．4％），客观缓解率10．5％，临床获益率31．6％。中位无进展生存期5．0个月。获益患者再次出现疾病进展并给予阿那曲唑治疗后，由实体瘤RECISTl．0标准判断疗效：CR0例，PR1例（14．3％），SD2例（28．6％），PD4例（57．1％），客观缓解率14．3％，临床获益率42．9％。中位无进展生存期4．0个月。由CTCs标准判断疗效：CR0例，PR1例（14．3％），SD1例（14．3％），PD5例（71．4％），客观缓解率14．3％，临床获益率28．6％。中位无进展生存期3．0个月。两种评价方法比较，差异无统计学意义。但在判定时间上，CTCs标准较影像学标准早1个月。结论监测晚期三线内分泌治疗耐药乳腺癌患者CTCs中FAS的表达情况，给予雌激素治疗可取得一定疗效，并有可能恢复部分患者对芳香化酶抑制剂的敏感性，且无明显副作用。

Objective To explore the relationship between FAS expression in CTCs and estradiol thera- py in endocrine - resistant advanced breast cancer and the effect of estradiol in reversing endocrine - resistance. Methods 20 endocrine - resistant advanced breast cancer patients with FAS expression in CTCs were given es- tradiol 2 mg,three times a day untill the disease advanced. Then, anastrozole 1 mg/d was used. Ieonography and CTCs examination were implementation in every circle. Results Among 20 cases, 1 case dropped out. According to RECIST1.0：CR 0, PR 2 cases （I0.5 % ） , SD 5 cases （26.3 % ）, PD 12 cases （63.2%）. ORR was 10.5% ; clinical benefit was 36.8% ; mPFS was 6.0 months. According to CTCs ： CR 0, PR 2 cases （ 10.5 % ） , SD 4 cases （21.1%） ,PD13 cases（68.4% ）. ORR was 10.5% ;clinical benefit was 31.6% ;mPFS was 5.0 months. After the disease advanced,anastrozole was used. According to CTCs： CR 0, PR 1 （ 14.3% ） , SD 2 （ 28.6% ） , PD 4 （57.1% ）. ORR was 14.3% ; clinical benefit was 42.9% ; mPFS was 4.0 months. According to CTCs ： CR 0, PR 1 （ 14.3% ） ,SD 1 （ 14.3% ） ,PD 5（71.4% ） ;ORR was 14.3% ;clinical benefit was 28.6% ;mPFS was 3.0 months. There was no significant difference between the two exam methods, but CTCs can be detected earlier than iconography change. Conclusion Estradiol can provide clinical benefit for endocrine -resistant advanced breastcancer patient who has FAS expression in CTCs. Estradiol can reverse the aromatase inhibitor resistant in some cases with no serious adverse events.