Common breast cancer treatments 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 the drug to standard anti-estrogen therapy may not only reduce troublesome side effects such as hot flashes, but also slow tumor growth.
The findings represent a major step forward for women with estrogen receptor (ER)-positive breast cancer, potentially providing a gentler and more powerful treatment for the disease.
Targeting ER-positive breast cancer
Approximately 75% of breast cancers are classified as ER-positive. In these cancers, tumor cells rely on estrogen to grow and divide.
Standard treatment often involves anti-estrogen drugs, such as letrozole, which block the effects of hormones and slow cancer progression.
However, these treatments can cause menopause-like symptoms such as hot flashes, joint pain, and potential bone loss, which may cause some patients to discontinue treatment.
Megestrol Acetate: Double Benefits
Megestrol acetate has long been used to manage hot flashes in women caused by anti-estrogen therapy.
The PIONEER trial demonstrated that even low doses of megestrol acetate can directly slow tumor growth when combined with antiestrogen therapy.
In this study, postmenopausal women with ER-positive breast cancer were treated with letrozole alone or in combination with low-dose (40 mg) or high-dose (160 mg) megestrol acetate for 2 weeks before surgery.
Tumor growth rates were measured at the beginning and end of this “window of opportunity” period.
Early results can be expected
The results of this study revealed that patients who received megestrol acetate in combination with letrozole experienced a significant reduction in actively dividing tumor cells compared to patients treated with letrozole alone. Interestingly, both low and high doses of megestrol acetate showed comparable anticancer effects.
The results of this study suggest that lower doses of megestrol acetate may provide the same therapeutic effects, with fewer side effects such as weight gain and hypertension that are typically associated with higher doses. This may make long-term use more tolerable for patients while maintaining efficacy.
Insights from the lab
In support of these clinical results, laboratory studies by researchers at Cancer Research UK’s Cambridge Institute demonstrated that progesterone slows the division of ER-positive breast cancer cells by indirectly blocking estrogen receptors.
Mouse models further confirmed that the combination of progesterone and anti-estrogen therapy slowed tumor growth more effectively than anti-estrogen therapy alone.
These results provided a strong rationale for testing patients with megestrol acetate, despite previous concerns that hormone-based treatments may promote tumor growth.
The PIONEER trial provided clear evidence that targeting progesterone receptors in parallel with antiestrogen therapy can be safe and beneficial.
Impact on patients
Megestrol acetate’s dual action (inhibiting tumor growth while reducing side effects such as hot flashes) may improve compliance with anti-estrogen therapy and improve treatment outcomes for thousands of women.
This approach could ensure more consistent treatment over time by addressing the unpleasant symptoms that often cause patients to discontinue their medications.
But researchers cautioned that the trial only assessed short-term effects. Longer-term studies are needed to confirm that low doses of megestrol acetate can maintain anticancer effects over months or years without increasing side effects.
Megestrol acetate is off-patent and could be an affordable addition to breast cancer treatment, making it available to a broader patient population.
If future studies confirm these initial findings, the drug could be widely used as an adjunct to anti-estrogen therapy.
next step
The Cambridge team plans to expand the study to a larger group of patients and longer treatment durations to further evaluate the benefits and safety of megestrol acetate in combination with antiestrogen therapy.
This research may 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 combination with conventional antiestrogen therapy.
Its ability to inhibit tumor growth while alleviating common side effects could represent a potential game changer in the management of ER-positive breast cancer, providing patients with a more effective and better-tolerated treatment.
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