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

USA: A recent study published in Clinical Cancer Research has shown that estrogens that stimulate the estrogen receptor can also effectively treat advanced or metastatic estrogen receptor-positive (ER+) breast cancer. The results support cyclical estrogen/anti-estrogen therapy as a promising strategy to treat advanced/metastatic ER+ breast cancer.the 

Advanced or metastatic estrogen receptor-positive breast cancer is commonly treated with drugs that block the estrogen receptor. Building on their previous studies, researchers at Dartmouth Cancer Center recently concluded a Phase II clinical trial to test the efficacy of alternating between estrogen stimulation and estrogen deprivation in patients with metastatic ER+ breast cancer and to identify tumour characteristics that predict who might benefit from this strategy.

The POLLY trial stands for “Phase II study of Pre-emptive oscillation of ER activity levels through the alternation of estradiol/anti-estrogen therapies prior to disease progression in ER+/HER2- metastatic or advanced breast cancer.” Among 19 patients enrolled in the trial, 3 (16%) experienced tumor shrinkage during cyclical treatment and another 5 (26%) had disease stabilization for at least 24 weeks, yielding an overall benefit rate of 42%. Treatments were well-tolerated, and no patients discontinued drug treatment due to side effects. Following cancer progression on cyclical treatment, 12 patients elected to receive non-cycling treatment with a single drug-5 of these patients (42%) had further disease stabilization lasting at least 24 weeks.

“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.