Low-Dose Megestrol Added to Letrozole Beneficial in ER-Positive Breast Cancer

TUESDAY, Jan. 6, 2026 (HealthDay News) — Low-dose megestrol added to letrozole is associated with a greater reduction in proliferation among postmenopausal women with estrogen receptor (ER)-positive breast cancer, according to a study published online Jan. 5 in Nature Cancer.

Rebecca A. Burrell, from the Cancer Research U.K. Cambridge Center, and colleagues reported a 198-patient, three-arm randomized phase IIb preoperative window-of-opportunity study, which examined the anti-estrogen letrozole with or without the progesterone mimic, megestrol, at 40 mg or 160 mg daily among postmenopausal women with ER-positive breast cancers. The treatment was given for two weeks prior to surgery. The primary end point was change in tumor proliferation as measured by Ki67 immunohistochemistry.

The researchers observed a greater reduction in proliferation when megestrol was added to letrozole, meeting the primary end point; comparable effects were seen with 40 and 160 mg of megestrol (mean Ki67 suppression for letrozole, letrozole + 40 mg megestrol, and letrozole + 160 mg megestrol: 71.4, 79.5, and 80 percent, respectively). Reduced ER genomic binding was seen at canonical binding sites, indicating reduced ER transcriptional activity.

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

Two authors disclosed ties to the pharmaceutical industry.

Abstract/Full Text