A common breast cancer treatment may soon become even more effective thanks to megestrol acetate, a synthetic hormone that mimics progesterone.
New research from the University of Cambridge suggests that adding this drug to standard anti-oestrogen therapy not only eases troublesome side effects like hot flushes but may also slow tumour growth.
The findings could mark a significant step forward for women with oestrogen receptor (ER)-positive breast cancer, offering a treatment that is both gentler on the body and more powerful against the disease.
Targeting ER- positive breast cancer
Around 75% of breast cancers are classified as ER-positive. In these cancers, tumour cells rely on oestrogen to grow and divide.
Standard treatment often involves anti-oestrogen medications, such as letrozole, which block the hormone’s effects and inhibit cancer progression.
However, these therapies can trigger menopause-like symptoms, including hot flushes, joint pain, and potential bone loss, which may prompt some patients to discontinue treatment.
Megestrol acetate: A dual benefit
Megestrol acetate has long been used to help women manage hot flushes caused by anti-oestrogen therapy.
The PIONEER trial now demonstrates that even a low dose of megestrol acetate may directly slow tumour growth when combined with anti-oestrogen treatment.
In the trial, post-menopausal women with ER-positive breast cancer were treated with letrozole alone or in combination with either a low dose (40mg) or high dose (160mg) of megestrol acetate for two weeks prior to surgery.
Tumour growth rates were measured at the start and end of this ‘window of opportunity’ period.
Promising early results
The trial’s results revealed that patients receiving megestrol acetate alongside letrozole experienced a greater reduction in actively dividing tumour cells compared to those treated with letrozole alone. Interestingly, both the low and high doses of megestrol acetate showed comparable anti-cancer effects.
The findings suggest that lower doses of megestrol acetate may provide the same therapeutic benefit with fewer side effects, such as weight gain or high blood pressure, commonly associated with higher doses. This could make long-term use more tolerable for patients while maintaining efficacy.
Insights from the lab
Supporting these clinical findings, laboratory studies by researchers at the Cancer Research UK Cambridge Institute demonstrated that progesterone slows the division of ER-positive breast cancer cells by indirectly blocking the oestrogen receptor.
Mouse models further confirmed that combining progesterone with anti-oestrogen therapy slowed tumour growth more effectively than anti-oestrogen treatment alone.
These results offered a strong rationale for testing megestrol acetate in patients, despite previous concerns that hormone-based therapies might promote tumour growth.
The PIONEER trial provided clear evidence that targeting the progesterone receptor alongside anti-oestrogen therapy can be safe and beneficial.
Implications for patients
Megestrol acetate’s dual action – reducing tumour growth while alleviating side effects like hot flushes – could improve adherence to anti-oestrogen therapy and enhance outcomes for thousands of women.
By addressing the uncomfortable symptoms that often lead patients to discontinue medication, this approach could ensure more consistent treatment over time.
Researchers caution, however, that the trial only assessed short-term effects. Longer-term studies are needed to confirm that low-dose megestrol acetate maintains its anti-cancer benefits without increasing side effects over months or years.
Because megestrol acetate is off-patent, it represents a potentially affordable addition to breast cancer treatment, making it accessible to a broad patient population.
If future studies confirm these early findings, the drug could become a widely used adjunct to anti-oestrogen therapy.
Next steps
The Cambridge team plans to expand research to larger patient groups and longer treatment durations to further evaluate the benefits and safety of megestrol acetate in combination with anti-oestrogen therapies.
This research could lead to new treatment protocols that improve both survival and quality of life for women with ER-positive breast cancer.
The PIONEER trial highlights megestrol acetate as a promising companion to conventional anti-oestrogen therapy.
Its ability to reduce tumour growth while mitigating common side effects positions it as a potential game-changer in the management of ER-positive breast cancer, offering patients a treatment that is both more effective and more tolerable.
