{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:21:35Z","timestamp":1785424895819,"version":"3.56.0"},"reference-count":30,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NHS"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Oral progestogens, including megestrol acetate (MA) and medroxyprogesterone acetate (MPA), have largely been superseded by aromatase inhibitors, tamoxifen, and selective oestrogen receptor degraders (SERDs) in oestrogen receptor-positive (ER-positive) metastatic breast cancer. However, they remain an option as late-line therapy after failure of standard treatments. Contemporary data are limited, particularly in patients previously treated with CDK4\/6 inhibitors. Methods: We conducted a multi-site retrospective analysis of patients with ER-positive metastatic breast cancer treated with MA or MPA between 2014 and 2024 at four hospital sites across London, United Kingdom. Patients were identified using pharmacy dispensing records. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan\u2013Meier method and Cox regression. Subgroup analyses included prior CDK4\/6 inhibitor exposure, histology and liver metastases. Results: A total of 116 patients were included. Median PFS was 2.4 months (95% CI 2.2\u20132.9), and median OS was 3.3 months (95% CI 2.7\u20134.9). Prior CDK4\/6 inhibitor exposure was associated with shorter PFS (1.9 vs. 2.8 months; HR 1.59; 95% CI 1.08\u20132.35, p = 0.019) and a trend toward shorter OS (3.1 vs. 3.6 months; HR 1.18, 95% CI 0.80\u20131.75, p = 0.41). Similarly, liver metastases were associated with shorter PFS (2.3 vs. 2.8 months; HR 1.78, 95% CI 1.12\u20132.85, p = 0.015), with a trend toward worse OS (3.1 vs. 4.9 months; HR 1.45, 95% CI 0.93\u20132.25, p = 0.103). A subset of patients derived prolonged benefit, with a 6-month PFS rate of 16%. Toxicity was manageable; thromboembolic events and oedema occurred in 9% and 11% of patients respectively. Appetite improvement was reported in 10%. Conclusions: MA and MPA demonstrated modest but clinically relevant late-line activity in heavily pretreated, endocrine-refractory ER-positive metastatic breast cancer. While prior exposure to CDK4\/6 inhibitors was associated with shorter PFS, patients without liver metastases appeared to derive the greatest benefit. These findings support a role for oral progestogens in selected patients who have exhausted standard therapeutic options.<\/jats:p>","DOI":"10.3390\/cancers18081191","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T09:49:44Z","timestamp":1775641784000},"page":"1191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and Safety of Oral Progestogens (Megestrol Acetate and Medroxyprogesterone Acetate) in Heavily Pretreated Oestrogen Receptor-Positive Metastatic Breast Cancer: A 10-Year Multi-Site Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7193-987X","authenticated-orcid":false,"given":"Iseult M.","family":"Browne","sequence":"first","affiliation":[{"name":"The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK"},{"name":"The Institute of Cancer Research, London SW3 6JB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng Chun","family":"Wong","sequence":"additional","affiliation":[{"name":"The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tazia","family":"Irfan","sequence":"additional","affiliation":[{"name":"The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Chan","sequence":"additional","affiliation":[{"name":"The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R. D.","family":"Johnston","sequence":"additional","affiliation":[{"name":"The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2692-0369","authenticated-orcid":false,"given":"Zoe","family":"Kemp","sequence":"additional","affiliation":[{"name":"The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4912-8502","authenticated-orcid":false,"given":"Emma","family":"Kipps","sequence":"additional","affiliation":[{"name":"The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Parton","sequence":"additional","affiliation":[{"name":"The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas C.","family":"Turner","sequence":"additional","affiliation":[{"name":"The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK"},{"name":"The Institute of Cancer Research, London SW3 6JB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2068-2593","authenticated-orcid":false,"given":"Alicia F. C.","family":"Okines","sequence":"additional","affiliation":[{"name":"The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK"},{"name":"The Institute of Cancer Research, London SW3 6JB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1016\/S0140-6736(16)32389-3","article-title":"Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): An international, randomised, double-blind, phase 3 trial","volume":"388","author":"Robertson","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3246","DOI":"10.1200\/JCO.22.00338","article-title":"Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor\u2013Positive, Human Epidermal Growth Factor Receptor 2\u2013Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial","volume":"40","author":"Bidard","year":"2022","journal-title":"J. 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