A phase II trial of low-dose estradiol in postmenopausal women with advanced breast cancer and acquired resistance to aromatase inhibition. Issue 18 (December 2015)

• Record Type: Journal Article
• Authors: Zucchini, G.; Armstrong, A.C.; Wardley, A.M.; Wilson, G.; Misra, V.; Seif, M.; Ryder, W.D.; Cope, J.; Blowers, E.; Howell, A.; Palmieri, C.; Howell, S.J.
• Is Part Of: European journal of cancer. Volume 51:Issue 18(2015:Dec.)
• Page Start: 2725
• Page End: 2731
• Publication Date: 2015-12
• Subjects: Breast cancer -- Endocrine -- Aromatase inhibitor -- Oestrogen -- Low dose; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2015.08.028
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: High-dose oestrogen (HDE) is effective but toxic in postmenopausal women with advanced breast cancer (ABC). Prolonged oestrogen deprivation sensitises BC cell lines to estrogen and we hypothesised that third-generation aromatase inhibitors (AIs) would sensitise BCs to low-dose estradiol (LDE). Methods: A single-arm phase II study of LDE (2 mg estradiol valerate daily) in postmenopausal women with estrogen receptor-positive (ER+) ABC. The primary end-point was clinical benefit (CB) rate. If LDE was ineffective, HDE was offered. If LDE was effective, retreatment with the pre-LDE AI was offered on progression. Results: Twenty-one patients were recruited before the trial was closed early due to slow accrual; 19 were assessable for efficacy and toxicity. CB was seen in 5 in 19 patients (26%; 95% confidence interval 9.1–51.2%), all with prolonged SD (median duration 16.8 months; range 11.0–29.6). Treatment was discontinued for toxicity in 4 in 19 patients (21%) and 8 in 11 women without hysterectomy experienced vaginal bleeding (VB). After primary LDE failure, three patients received HDE and one achieved a partial response (PR). Following CB on LDE, four patients restarted pre-LDE AI and three achieved CB including one PR. Those with CB to LDE had a significantly longer duration of first-line endocrine therapy for ABC than those without (54.9 versus 16.8 months; p < 0.01) Conclusion: LDE is an effective endocrine option in women with evidence of prolonged sensitivity to AI therapy. LDE is reasonably well tolerated although VB is an issue. Re-challenge with the pre-LDE AI following progression confirms re-sensitisation as a true phenomenon.