ER mutations may be useful in identifying patients who are likely to benefit from this treatment strategy.Todd W. Miller, PhD
Results from a new clinical trial led by Dartmouth Cancer Center researcher Todd W. Miller, PhD, and medical oncologist Gary N. Schwartz, MD are in. The trial showed that cycling between estrogen-stimulating and estrogen-blocking therapies is an effective treatment for patients with metastatic or advanced estrogen receptor (ER)-positive breast cancer.
Advanced or metastatic ER+ breast cancer is commonly treated with drugs that block the estrogen receptor. However, estrogens that stimulate the receptor can also be effective. Building on their previous studies, Miller and Schwartz recently concluded a Phase II clinical trial that cycled between estrogen stimulation and estrogen deprivation in patients with metastatic ER+ breast cancer. The trial also allowed them to identify tumor characteristics that predict who might benefit from this strategy. The results, newly published in Clinical Cancer Research, support cyclical estrogen/anti-estrogen therapy as a promising strategy.
Among 19 patients enrolled in the POLLY trial, 3 (16%) experienced tumor shrinkage during cyclical treatment and another 5 (26%) had disease stabilization for at least 24 weeks, for an overall benefit rate of 42%. Treatments were well-tolerated, and none of the 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 more than 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 tumor-targeted drugs coming to market in the past decade such as Ibrance, Kisqali, Verzenio and Afinitor, remain under-developed,” says Schwartz. “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 Miller. “In the POLLY trial, we found that gene mutations that are often present in tumors that become resistant to anti-estrogen drugs, were present in tumors from the only two patients whose tumors shrank in response to estrogen therapy within the first 8 weeks. This suggests that ER mutations may be useful in identifying patients who are likely to benefit from this treatment strategy.”
The team will build on POLLY findings by holding a follow-up clinical study to test the effectiveness of estrogen therapy in patients with or without tumor mutations in ER.