A new study out of the United Kingdom is making waves in the breast cancer research community. The phase 2b PIONEER trial, published in Nature Cancer, reveals that adding megestrol acetate—a synthetic progesterone—to standard letrozole therapy can further suppress tumor growth for postmenopausal women with early-stage, estrogen receptor (ER)-positive breast cancer. The numbers tell the story: mean Ki67 suppression, a key marker for tumor proliferation, reached about 80% with the megestrol and letrozole combo, compared to just 71.4% with letrozole alone.
How the PIONEER Trial Was Conducted
The PIONEER trial (NCT03306472) enrolled 244 women newly diagnosed with early-stage, ER-positive, HER2-negative breast adenocarcinoma across 10 hospitals in the UK. Patients were randomized into three main arms. Arm A (51 patients) received only letrozole (2.5 mg daily). Arm B and Arm C—each with 91 participants—received letrozole combined with either 40 mg or 160 mg of megestrol, respectively. The results showed that both doses of megestrol, when paired with letrozole, led to greater tumor suppression than letrozole alone.
Benefits and Side Effects: A Mixed Picture
Besides its antiproliferative punch, megestrol acetate appears to pull double duty by easing some of the notorious side effects of letrozole. Multiple studies, including the PIONEER trial, confirm that even low-dose megestrol can significantly reduce the frequency and severity of hot flashes—an unwelcome symptom for many undergoing hormone therapy. But it’s not all smooth sailing: megestrol itself can introduce side effects such as weight gain, raised blood pressure, facial swelling, and, less commonly, an increased risk of blood clots or paradoxical hot flashes.
The research team, led by scientists from Cambridge, notes that their data support further exploration of lower-dose megestrol in combination therapies. The trial’s funding came from several major organizations, including the AntiCancer Fund and Cancer Research UK, adding credibility to the findings.
For patients and clinicians alike, these results offer a promising new angle in the fight against early-stage ER-positive breast cancer—one that may not only slow tumor growth but also improve quality of life during treatment. Still, as with all therapies, a careful weighing of benefits and risks remains essential.
