A pilot study of estradiol followed by exemestane for reversing endocrine resistance in postmenopausal women with hormone receptor-positive metastatic breast cancer.

Abstract

BACKGROUND:

Endocrine resistance is a frequent complication, and strategies to reverse it are a high research priority for metastatic breast cancer (MBC) that is hormone receptor positive. Preclinical data suggest re-exposure to estrogen induces tumor regression in tamoxifen-resistant tumors. We conducted a pilot study to determine whether short-term estradiol exposure would reverse endocrine resistance and resensitize tumors

METHODS:

Postmenopausal women with estrogen receptor-positive MBC whose disease had progressed after receiving at least one prior endocrine therapy were eligible for the study. Patients were initially treated with 6 mg/day estradiol, and those who had not progressed after 3 months were then switched to exemestane.

RESULTS:

Thirteen patients were evaluable for toxicity and response. No grade 3 or 4 toxicities were observed. Of the 13 patients who initiated estradiol therapy, 6 patients (46%) had not experienced disease progression at month 3 and were switched to exemestane. On exemestane, disease progression was documented in five patients, with one having stable disease as best response. Median progression-free survival for all patients was 4.8 months (range: 0.6-9.5 months).

CONCLUSION:

Treatment with an estrogen prior to resuming antiestrogen treatments was not effective at reversing hormone resistance; however, low-dose estradiol treatment had measurable clinical activity with minimal toxicity and should be considered as a therapeutic option for hormone-refractory MBC.

• Authors: Pavani Chalasani, Alison Stopeck, Kathryn Clarke, Robert Livingston
• Journal: The oncologist (Oncologist) Vol. 19 Issue 11 Pg. 1127-8 (Nov 2014) ISSN: 1549-490X [Electronic] England
• PMID: 25260365 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©AlphaMed Press; the data published online to support this summary is the property of the authors.

Chemical References

• Androstadienes
• Antineoplastic Agents
• Estrogen Receptor Modulators
• Receptors, Estrogen
• Estradiol
• exemestane

Topics

• Aged
• Aged, 80 and over
• Androstadienes (adverse effects, therapeutic use)
• Antineoplastic Agents (adverse effects, therapeutic use)
• Breast Neoplasms (drug therapy, metabolism, mortality, pathology)
• Drug Resistance, Neoplasm (drug effects)
• Estradiol (adverse effects, therapeutic use)
• Estrogen Receptor Modulators (pharmacology)
• Female
• Humans
• Middle Aged
• Pilot Projects
• Postmenopause
• Receptors, Estrogen (metabolism)
• Treatment Outcome