Alternating oestrogen and anti-oestrogen therapies is effective in treating metastatic breast cancer

16 May 2023
Alternating oestrogen and anti-oestrogen therapies is effective in treating metastatic breast cancer

Advanced or metastatic oestrogen receptor-positive (ER+) breast cancer is commonly treated with drugs that block the oestrogen receptor.

However, oestrogens that stimulate the receptor can also be effective.  

Building on their previous studies, researchers at Dartmouth Cancer Center recently concluded a Phase II clinical trial aimed to test the efficacy of alternating between oestrogen stimulation and oestrogen deprivation in patients with metastatic ER+ breast cancer, and to identify tumour characteristics that predict who might benefit from this strategy.

The results, newly published ahead of print in Clinical Cancer Research, a journal of the American Association for Cancer Research, support cyclical oestrogen/anti-oestrogen therapy as a promising strategy to treat advanced/metastatic ER+ breast cancer.

The POLLY trial stands for “Phase II study of Pre-emptive oscillation of ER activity levels through alternation of oestradiol/anti-oestrogen therapies prior to disease progression in ER+/HER2- metastatic or advanced breast cancer.”

Among 19 patients enrolled in the trial, 3 (16%) experienced tumour shrinkage during cyclical treatment and another 5 (26%) had disease stabilisation 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 stabilisation lasting at least 24 weeks.

“Oestrogen therapy has been used for more than 50 years to treat breast cancer. Strategies to maximise oestrogen efficacy and minimise 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.”

“Tumour features called biomarkers that predict which patients will benefit from oestrogen 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 tumours that become resistant to anti-oestrogen drugs, were present in tumours from the only two patients whose tumours shrank in response to oestrogen 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 conducting a follow-up clinical study, “Oestradiol therapy to target ER-mutant and ER-wild-type ER+ metastatic breast cancer (ESTHER),” that will test the effectiveness of oestrogen therapy in patients with or without tumour mutations in ER.

Article: Alternating 17beta-oestradiol and aromatase inhibitor therapies is efficacious in post-menopausal women with advanced endocrine-resistant ER+ breast cancer

Source: Dartmouth Health