| PurposeFulvestrant is a selective ER antagonist that induces a conformational change, leading to degradation and downregulation of the ER protein. A number of global studies have confirmed that fulvestrant was at least as effective as the third-generation aromatase inhibitors for the treatment of postmenopaosal women with advanced ER positive BC after failure of pior antiestrogen therapy. In clinical practise, the rise of oestradiol level which has been regarded as risk factors of breast cancer, is common during the using of fulvestrant in postmenopausal BC.Farlow et al. have demonstrated that breast cancer patients with high levels of estrogen are associated to high risk of recurrence and metastasis by analysising the relationship between endogenous hormones and postmenopausal breast cancer[1]. This study aims to observe the change of estrogen levels before and after the treatment period of fulvestrant in metastatic breast cancer patients, and to analyze the correlation between the changes and the efficacy of fulvestrant, providing the real clinical data for the clinical decision making. MethodsFifty-one hormone receptor-positive MBC patients who had sexual hormone determinations during the treatment period of fulvestrant were enrolled. To evaluate the curative effect of fulvestrant in postmenopausal patients and premenopausal patients.According to the menstrual conditions are divided into postmenopausal group, the premenopausal group, to describe the changes of estrogen before and after fulvestrant treatment each of the group, and to analyze the correlation with efficacy. All patients were treated with fulvestrant injection therapy, doses: fulvestrant 500 mg, time: the first day, the first 14 days, 28 days, 28 days for a cycle, mode: intramuscular injection; premenopausal patients are also plus Zoladex(goserelin injection) 3.6mg, injected subcutaneously, once every 28 days. Result1.Thirty-five MBC patients were postmenopausal,the patients’ median age was 57(46~83); Overall response rate(ORR) was 5.71%(2/35), thirteen patients(17.9%) experienced clinical benefit(CBR), median progression free survival(PFS) was 3.0 months(1~18 months). The patients with adjuvant endocrine therapy were benefit more from the regimen. Median level of E2 was significantly higher after the treatment of Fulvestrant(13.9 pg / ml vs 72.5 pg / ml, respectively; P=0.012). Median FSH before and afrer the treatment was 52.6 IU / L and 53.3 IU / L which shown no significant difference.Ten patients(41.7%) whose difference of E2 level before and after treatment of fulvestrant was <100.28 pg / ml had median 8 months’ PFS and and the CBR was 42.9%. 14 patients(58.3%) whose difference of E2 level was ≧100.28 pg / ml had median 13 months’ PFS and the CBR was 30%. Univariate analysis showed the increased E2 after the treatment of fulvestrant had no signifant correlation with PFS(p = 0.353). For those 17 patiets whose PFS were <6 months(68%) their median difference of E2 was 58.8 pg / ml; and for the others(32%) their median difference of E2 was 118.66 pg / ml. Thees difference between two group has no statistically significant(p = 0.288> 0.05).2.Sixteen MBC patients were premenopausal.The patients’ median age was 43(31~50); Nine patients(56.3%) experienced clinical benefit(CBR), overall response rate was 12.5%, median PFS was 6.0 months(2~10 months). The mean E2 of 9 patients who got clinical benefit was 159.07 pg / ml(SD 72.76 pg / ml). The E2 level was up to 280.11 pg / ml in a patient who got 10 months’ clinical benefit of the fulvestrant therapy. Alse,the mean E2 of the other 7 patients who have’t got clinical benefit of this therapy was 143.18 pg / ml(SD 49.35 pg / ml). The E2 level was 63.25 pg / ml in a patient who got rapidly disease progession of the fulvestrant therapy(PFS 2 months). Conclusion1.For postmenopausal HR positive MBC, fulvestrant can be used as the preferred treatment for the satisfactory effect. And for premenopausal patients with MBC, the combination of fulvestrant 500 mg and ovarian function inhibitors is also effective.2.The use of fulvestrant caused an increase of estradiol for postmenopausal MBC patients. But the increase of estradiol level has no correlation with the efficacy, so it couldn’t be used as an indicator of the evaluation of endocrine therapy3.For premenopausal HR positive MBC, the use of ovarian function inhibitors didn’t pull down the estrogen level during the use of fulvestrant.. The correlation between the estrogen level and the effcacy still need expanding samples to verify.in the future. |
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