Cyclical estrogen and anti-estrogen therapy effective for treatment of metastatic breast cancer

“Estrogen therapy has been used for over 50 years to treat breast cancer. Strategies to maximize estrogen efficacy and minimize side effects, as well as research on cancers that develop resistance to the new tumour-targeted drugs coming to market in the past decade, such as Ibrance, Kisqali, Verzenio and Afinitor, remain under-developed,” says Dartmouth Cancer Center breast oncologist and lead author, Gary N. Schwartz, MD. “The POLLY study addressed this gap.”

“Tumor features called biomarkers that predict which patients will benefit from estrogen therapy have also not been reported,” adds cancer researcher and co-corresponding author, Todd W. Miller, PhD. “In the POLLY trial, we found that mutations in the gene encoding ER, which often arise in tumors that become resistant to anti-estrogen drugs, were present in tumours from the only two patients whose tumours shrank in response to estrogen therapy within the first 8 weeks. This suggests that ER mutations may be useful in identifying patients likely to benefit from this treatment strategy.”

The team will build on POLLY findings by conducting a follow-up clinical study, “Estradiol therapy to target ER-mutant and ER-wild-type ER+ metastatic breast cancer (ESTHER),” that will test the effectiveness of estrogen therapy in patients with or without tumour mutations in ER.

Reference:

Gary N. Schwartz, Peter A. Kaufman, Karthik V. Giridhar, Jonathan D. Marotti, Mary D. Chamberlin, Bradley A. Arrick, Grace Makari-Judson, Matthew P. Goetz, Shannon M. Soucy, Fred Kolling, Eugene Demidenko, Todd W. Miller, https://doi.org/10.1158/1078-0432.CCR-23-0112.