Healthcare (Commonwealth Union) – A recent clinical study that was led by researchers in Cambridge has found that a drug designed to imitate the hormone progesterone can help suppress cancer growth when combined with standard anti-oestrogen therapy for breast cancer.
Low-dose megestrol acetate, a synthetic form of progesterone, is already prescribed to ease hot flushes caused by anti-oestrogen treatments, helping patients stay on their medication. Findings from the PIONEER trial now suggest that adding a small dose of megestrol may also provide a direct anti-tumour benefit when used alongside these therapies.
Approximately 75 per cent of breast cancers are classified as oestrogen receptor (ER) positive. These tumours rely on oestrogen for growth, as they contain high levels of oestrogen receptors. As a result, patients are typically treated with anti-oestrogen drugs that lower oestrogen levels, effectively starving the cancer. However, this approach often triggers menopause-like side effects, such as hot flushes, aches in the joints and muscles, and an increased risk of bone thinning.
In the PIONEER study, post-menopausal women with ER-positive breast cancer received anti-oestrogen therapy either alone or in combination with megestrol. After just two weeks, patients given the combined treatment showed a larger reduction in tumour growth rates compared with those receiving anti-oestrogen therapy on its own.
Although the results need to be validated in larger groups of patients and followed over a longer timeframe, researchers at the University of Cambridge say the trial indicates that megestrol may significantly enhance quality of life for thousands of women. For many patients, anti-estrogen therapies cause unpleasant side effects that can be severe enough to make some stop their treatment altogether.
The PIONEER study was led by Dr Richard Baird of the University of Cambridge’s Department of Oncology and an Honorary Consultant Medical Oncologist at Cambridge University Hospitals NHS Foundation Trust (CUH). He pointed out that compared with some chemotherapy treatments, anti-estrogen drugs are generally very effective and far easier for patients to tolerate, which is why many women remain on them for years. Dr Baird indicated however, a subset of patients experience side effects that interfere with daily life and when a treatment is taken long term, even side effects that seem mild can become quite burdensome.
Researchers also noted that some patients with ER-positive breast cancer have elevated levels of another protein called the progesterone receptor (PR). These patients tend to show a stronger response to anti-estrogen hormone therapy.
To understand the biological reason for this, Professor Jason Carroll and his team at the Cancer Research UK Cambridge Institute conducted experiments using cell cultures and mouse models. Their work demonstrated that progesterone slows the division of ER-positive cancer cells by indirectly inhibiting estrogen receptor activity, leading to reduced tumor growth. When progesterone was added to anti-estrogen treatment in mice, tumor growth slowed even further.
Professor Carroll, who is the co-lead of the Precision Breast Cancer Institute, says “These were very promising lab-based results, but we needed to show that this was also the case in patients. There’s been concern that taking hormone replacement therapy – which primarily consists of estrogen and synthetic versions of progesterone (called progestins) – might encourage tumor growth. Although we no longer think this is the case, there’s still been residual concern around the use of progesterone and progestins in breast cancer.”
For the purposes of exploring if combining progesterone receptor targeting with anti-estrogen therapy could lower tumor growth in patients, Dr Baird and Professor Carroll developed the PIONEER trial. The study evaluated the effect of adding the progestin megestrol to the standard anti-estrogen drug letrozole.
