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• A recent study found that a synthetic progesterone drug used to manage hot flashes in females with breast cancer may also help slow tumor growth. 
• A low dose of megestrol acetate is already currently used to help individuals manage hot flashes associated with anti-estrogen treatment.
• The PIONEER trial has found that combining this synthetic progesterone drug with the conventional anti-estrogen treatment may also have a direct anticancer effect. 

A drug that mimics the hormone progesterone may have anticancer activity when paired with conventional anti-estrogen treatments for females with breast cancer. 

That’s according to a new trial led by the University of Cambridge.

It’s already a proven treatment to provide a low dose of synthetic progesterone (megestrol acetate) to help manage side effects of anti-estrogen treatments, such as hot flashes.

However, the trial, dubbed PIONEER, found that the addition of megestrol to this treatment may also have a direct anticancer effect. The results were recently published in Nature Cancer. 

“These findings could have significant clinical impact by improving treatment adherence while positively impacting tumor control. However, further studies will be required to substantiate these claims,” said Esha Sachdev, MD, a breast medical oncologist at the MemorialCare Todd Cancer Institute at Long Beach Medical Center in Long Beach, CA. Sachdev wasn’t involved in the study. 

Debra Patt, MD, PhD, MBA, executive vice president of Public Policy and Strategy for Texas Oncology, who was not involved in the study, agreed.

“I think the study is exciting and should be expanded so we know how it might impact long-term outcomes in women with breast cancer,” Patt told Healthline.

Anticancer properties of progesterone-like drug

Around three-quarters of all breast cancers are ER-positive. This means that breast cancer has strong estrogen receptors, which are proteins located on or within cells that can bind to specific substances in the blood. 

Breast cancer cells that are taken out during a biopsy or surgery are tested for estrogen and progesterone receptors. If the cells have either of these receptors, it means that when the hormone attaches to the receptor, it stimulates cancer growth. 

Individuals with ER-positive breast cancer are often offered anti-estrogen medications to reduce the level of estrogen, depriving the cancer of estrogen and inhibiting its growth. However, reducing the estrogen levels can also lead to side effects that are similar to menopause symptoms, including: 

• hot flashes
• potential bone loss
• joint and muscle pain

“One proposed mechanism as to why the megestrol reduces tumor growth is through improving adherence to adjuvant endocrine therapy by alleviating hot flashes, which is achieved with megestrol 40 milligrams,” Sachdev said. 

“A second mechanism for the effectiveness of megestrol is the direct antiproliferative effect on tumor cells mediated by reduced ER genomic binding, subsequently antagonizing estrogen signaling. The lower dose may be sufficient to saturate receptors and therefore reduce ER chromatin binding,” she noted. 

In the PIONEER trial, a total of 198 postmenopausal females with ER-positive breast cancer were recruited from 10 hospitals in the United Kingdom. The participants were randomized into three groups: 

• only received letrozole, a medication that blocks estrogen and is used as a treatment for ER-positive breast cancer
• received letrozole and 40 mg of megestrol daily
• received letrozole and 160 mg of megestrol daily

The treatment was given to each participant for two weeks prior to surgery to remove the tumor. The percentage of actively growing tumor cells was assessed both at the start of the trial and then again just before surgery. 

After the two weeks, those who received the combination of medications saw a greater decrease in tumor growth rates compared to those who were only treated with the anti-estrogen medication. 

“In the two-week window that we looked at, adding a progestin made the anti-oestrogen treatment more effective at slowing tumour growth. What was particularly pleasing to see was that even the lower dose had the desired effect,” Rebecca Burrell, joint first author of the study and clinical research associate with Cambridge University Hospitals and Cancer Research UK Cambridge Institute, said in a press release,

“Although the higher dose of progesterone is licensed as an anti-cancer treatment, over the long term it can have side effects, including weight gain and high blood pressure. But just a quarter of the dose was as effective, and this would come with fewer side effects,” she continued.

Future of breast cancer treatment

The PIONEER trial shows that the combination of megestrol and anti-estrogen medications may make a difference for certain females with ER-positive breast cancer. 

However, further research is required with larger cohorts and a longer time period.

“Several additional studies are needed to strengthen and validate the results from this trial,” Sachdev told Healthline. “A longer duration is necessary to assess safety and tolerability in conjunction with efficacy.”

“We are in a time of incredible research in breast cancer, and breast cancer patients have every reason to be optimistic about their future,” Pratt said.

“As I have observed multidisciplinary cancer care evolve tremendously over time, we can do more and more to help women live a long and healthy life.”