Effects of ovarian ablation or suppression on breast cancer recurrence and survival: patient-level meta-analysis of 15 000 women in 23 randomised trials
Year: 2026
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: BACKGROUND: For premenopausal women with oestrogen receptor (ER)-positive early breast cancer, the additional protective effect of ovarian function suppression (OFS, by ablation or drugs) may depend on menopausal status after any chemotherapy, and tamoxifen usage. We assess the effects of OFS on breast cancer outcomes among premenopausal women and how they vary by patient or tumour characteristics and receipt of other treatments. METHODS: We conducted a meta-analysis of individual participant data from the randomised trials comparing OFS versus no OFS, in women with ER-positive or ER-unknown early breast cancer who were premenopausal at randomisation and younger than 55 years. Trials were categorised by whether premenopausal status was or was not confirmed after chemotherapy (if given), and by allocation to tamoxifen. Primary outcomes were invasive breast cancer recurrence, breast cancer mortality, other mortality, and all-cause mortality. ER-weighted log-rank methods estimated event rate ratios (RRs) for ER-positive disease. FINDINGS: Datasets were provided for 23 of 25 identified eligible trials, comprising 18 851 (98·9%) of 19 053 randomly assigned women. Among 15 075 premenopausal women with ER-positive or ER-unknown tumours, allocation to OFS significantly reduced recurrence rates (RR 0·82, 95% CI 0·77-0·87; p<0·00001), with larger reductions in women who were confirmed premenopausal after chemotherapy (or who did not receive chemotherapy) than in those with unconfirmed premenopausal status after chemotherapy; heterogeneity p=0·0004. Among confirmed premenopausal women, recurrence reductions were larger in older trials without tamoxifen (RR 0·61, 0·52-0·71; p<0·0001) than in more recent trials of OFS plus tamoxifen versus tamoxifen (RR 0·79, 0·70-0·91; p=0·0008). In these more recent trials, the additional recurrence reduction with OFS appeared larger in women younger than 45 years than in women aged 45-54 years (RR 0·73, 0·63-0·86 vs RR 0·95, 0·75-1·21; p=0·072); in those younger than 45 years, breast cancer mortality was similarly improved (RR 0·74, 0·58-0·94; p=0·012). There was no increase in deaths without recurrence. Findings did not differ significantly by OFS method or other recorded patient or tumour characteristics. INTERPRETATION: For premenopausal women with ER-positive early breast cancer, even if chemotherapy or tamoxifen are given, OFS significantly reduces the 15-year risk of recurrence and death. FUNDING: Nuffield Department of Population Health, University of Oxford; Cancer Research UK; the Breast Cancer Research Foundation; and the UK Medical Research Council.
Source: The Lancet
Authors: Rosie Bradley, Jeremy Braybrooke, Mike Clarke, Robert K Hills, Amanda Kerr, Richard Peto, David Dodwell, Paul McGale, Hongchao Pan, Carolyn Taylor, Rodrigo Arriagada, Judith Bliss, Allan Hackshaw, Hyun-Ah Kim, Woo Chul Noh, John Yarnold, Graham Beake, Richard Berry, Clare Boddington, Christina Davies, Lucy Davies, Fran Duane, Vaughan Evans, Jo Gay, Lucy Gettins, Jon Godwin, Francesca Holt, Sam James, Hui Lui, Zulian Lui, Elizabeth MacKinnon, Gurdeep Mannu, Theresa McHugh, Philip Morris, Mariko Nakahara, Simon Read, Ewan Straiton, Hannah Taylor, Muneera B Masood, Dennis Parker, John J Price, Caroline Lohrisch, Alan Nichol, Yi Shan, Yong Fu Shao, Xiang Wang, Binghe Xu, Dong-Bing Zhao, Anthony Howell, Ric Swindell, Robert L Comis, Robert J Gray, Nicholas J Robert, George W Sledge, Lawrence J Solin, Joseph A Sparano, Douglass C Tormey, William Wood, Thierry Delozier, Marc Spielman, Josette Mace Lesec'h, Wolfgang Eiermann, Joern Hilfrich, Walter Jonat, Manfred Kaufmann, Rolf Kreienberg, Martin Schumacher, Roger A'Hern, Paul Ellis, Lucy Kilburn, Monica M Castiglione, Alan Coates, Marco Colleoni, John Collins, John J Forbes, Richard Gelber, Aron Goldhirsch, Jurij Lindtner, Olivia Pagani, Karen N Price, Carl-Magnus Rudenstam, Hans-Jörg Senn, Beat Thürliman, Claire E D Chilvers, Charles R Coombes, Marc Espie, Emma Hall, Michel Marty, Shoushu Mitsuyama, Yasuo Nomura, Shin-ichiro Ohno, Stewart Anderson, Hanna Bandos, Ann Brown, John Bryant, Reena Cecchini, Joe Costantino, James Dignam, Bernie Fisher, Charles Geyer, Eleftherios Mamounas, Soonmyung Paik, Carol K Redmond, Edward Romond, Gong Tang, Mylin A Torres, Lawrence Wickerham, Norman Wolmark, Grey Yothers, Bjørn K Erikstein, Sverre Gundersen, Martin Hauer-Jensen, Herman Høst, Anne-Birgitte Jacobsen, Roar Nissen-Meyer, Carla I Falkson, Arthur J S Bryant, G H Ewing, L A Firth, Judy Krushen-Kosloski, Kathy Albain, William Barlow, George T Budd, Julie Gralow, Daniel Hayes, Gabriel Hortobagyi, Reshma Jagsi, Silvana Martino, Lajos Pusztai, Priyanka Sharma, Alastair Thompson, Alexander H G Paterson, Kathleen I Pritchard, Anthony Fyles, J William Meakin, Tony Panzarella, Michael Baum, Tommy Fornander, Antonio Nicolucci, Bo Nordenskjold, Richard Sainsbury, David Cameron, Karla Ballman, John Bartlett, Elizabeth Bergsten-Nordström, Etienne Brain, Lisa Carey, Almona Choudhury, Robert Coleman, Jack Cuzick, Lucia Del Mastro, Mitch Dowsett, Bent Ejlertsen, Theodoros Foukakis, Jose Angel Garcia-Saenz, Michael Gnant, Matthew P Goetz, Pamela Goodwin, Catherine Hill, Wolfgang Janni, Sibylle Loibl, Stuart A McIntosh, Hirofumi Mukai, Valentina Nekljudova, Larry Norton, Martine Piccart, Philip Poortmans, Vinod Raina, Daniel Rea, John Robertson, Shigerhira Saji, Roberto Salgado, Dennis Slamon, Tanja Spanic, Patty Spears, Guenther Steger, Sandra J Thompson, Masakazu Toi, Andrew Tutt, Giuseppe Viale, Xiang Wang, Tim Whelan, Nicholas Wilcken, Antonio Wolff, Ke-Da Yu, Jonas Bergh, Sandra M Swain, Nancy E Davidson, Prudence A Francis, Meredith M Regan, Richard Gray
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $7,890
Awards: G3773004994, G4415725842
OpenAlex ID: W7160084041