1. Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression:a patient-level meta-analysis of 7030 women from four randomised trials
- Author
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Rosie Bradley, Jeremy Braybrooke, Richard Gray, Robert K Hills, Zulian Liu, Hongchao Pan, Richard Peto, David Dodwell, Paul McGale, Carolyn Taylor, Prudence A Francis, Michael Gnant, Francesco Perrone, Meredith M Regan, Richard Berry, Clare Boddington, Mike Clarke, Christina Davies, Lucy Davies, Fran Duane, Vaughan Evans, Jo Gay, Lucy Gettins, Jon Godwin, Sam James, Hui Liu, Elizabeth MacKinnon, Gurdeep Mannu, Theresa McHugh, Philip Morris, Simon Read, Ewan Straiton, Raimund Jakesz, Christian Fesl, Olivia Pagani, Richard Gelber, Michelino De Laurentiis, Sabino De Placido, Ciro Gallo, Kathy Albain, Stewart Anderson, Rodrigo Arriagada, John Bartlett, Elizabeth Bergsten-Nordström, Judith Bliss, Etienne Brain, Lisa Carey, Robert Coleman, Jack Cuzick, Nancy Davidson, Lucia Del Mastro, Angelo Di Leo, James Dignam, Mitch Dowsett, Bent Ejlertsen, Matthew Goetz, Pam Goodwin, Pat Halpin-Murphy, Dan Hayes, Catherine Hill, Reshma Jagsi, Wolfgang Janni, Sibylle Loibl, Eleftherios P Mamounas, Miguel Martín, Hirofumi Mukai, Valentina Nekljudova, Larry Norton, Yasuo Ohashi, Lori Pierce, Philip Poortmans, Kathleen I Pritchard, Vinod Raina, Daniel Rea, John Robertson, Emiel Rutgers, Tanja Spanic, Joseph Sparano, Guenther Steger, Gong Tang, Masakazu Toi, Andrew Tutt, Giuseppe Viale, Xiang Wang, Tim Whelan, Nicholas Wilcken, Norman Wolmark, David Cameron, Jonas Bergh, Sandra M Swain, Bradley, R., Braybrooke, J., Gray, R., Hills, R. K., Liu, Z., Pan, H., Peto, R., Dodwell, D., Mcgale, P., Taylor, C., Francis, P. A., Gnant, M., Perrone, F., Regan, M. M., Berry, R., Boddington, C., Clarke, M., Davies, C., Davies, L., Duane, F., Evans, V., Gay, J., Gettins, L., Godwin, J., James, S., Liu, H., Mackinnon, E., Mannu, G., Mchugh, T., Morris, P., Read, S., Straiton, E., Jakesz, R., Fesl, C., Pagani, O., Gelber, R., De Laurentiis, M., De Placido, S., Gallo, C., Albain, K., Anderson, S., Arriagada, R., Bartlett, J., Bergsten-Nordstrom, E., Bliss, J., Brain, E., Carey, L., Coleman, R., Cuzick, J., Davidson, N., Del Mastro, L., Di Leo, A., Dignam, J., Dowsett, M., Ejlertsen, B., Goetz, M., Goodwin, P., Halpin-Murphy, P., Hayes, D., Hill, C., Jagsi, R., Janni, W., Loibl, S., Mamounas, E. P., Martin, M., Mukai, H., Nekljudova, V., Norton, L., Ohashi, Y., Pierce, L., Poortmans, P., Pritchard, K. I., Raina, V., Rea, D., Robertson, J., Rutgers, E., Spanic, T., Sparano, J., Steger, G., Tang, G., Toi, M., Tutt, A., Viale, G., Wang, X., Whelan, T., Wilcken, N., Wolmark, N., Cameron, D., Bergh, J., Swain, S. M., Bradbury, R, Braybrooke, J, Gray, R, Hills, R, Liu, Z, Pan, H, Peto, R, Dodwell, D, and McGale, P
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Breast Neoplasms/pathology ,Antineoplastic Agents, Hormonal/therapeutic use ,Antineoplastic Agents, Hormonal ,Aromatase Inhibitors ,Breast Neoplasms ,Tamoxifen ,Neoplasm Recurrence, Local/drug therapy ,Tamoxifen/therapeutic use ,Oncology ,Receptors, Estrogen ,Chemotherapy, Adjuvant ,Humans ,Aromatase Inhibitor ,Female ,Aromatase Inhibitors/adverse effects ,Neoplasm Recurrence, Local ,Human ,Randomized Controlled Trials as Topic - Abstract
Background: For women with early-stage oestrogen receptor (ER)-positive breast cancer, adjuvant tamoxifen reduces 15-year breast cancer mortality by a third. Aromatase inhibitors are more effective than tamoxifen in postmenopausal women but are ineffective in premenopausal women when used without ovarian suppression. We aimed to investigate whether premenopausal women treated with ovarian suppression benefit from aromatase inhibitors. Methods: We did a meta-analysis of individual patient data from randomised trials comparing aromatase inhibitors (anastrozole, exemestane, or letrozole) versus tamoxifen for 3 or 5 years in premenopausal women with ER-positive breast cancer receiving ovarian suppression (goserelin or triptorelin) or ablation. We collected data on baseline characteristics, dates and sites of any breast cancer recurrence or second primary cancer, and dates and causes of death. Primary outcomes were breast cancer recurrence (distant, locoregional, or contralateral), breast cancer mortality, death without recurrence, and all-cause mortality. As distant recurrence invariably results in death from breast cancer several years after the occurrence, whereas locoregional recurrence and new contralateral breast cancer are not usually fatal, the distant recurrence analysis is shown separately. Standard intention-to-treat log-rank analyses estimated first-event rate ratios (RR) and their confidence intervals (CIs). Findings: We obtained data from all four identified trials (ABCSG XII, SOFT, TEXT, and HOBOE trials), which included 7030 women with ER-positive tumours enrolled between June 17, 1999, and Aug 4, 2015. Median follow-up was 8·0 years (IQR 6·1–9·3). The rate of breast cancer recurrence was lower for women allocated to an aromatase inhibitor than for women assigned to tamoxifen (RR 0·79, 95% CI 0·69–0·90, p=0·0005). The main benefit was seen in years 0–4 (RR 0·68, 99% CI 0·55–0·85; p Interpretation: Using an aromatase inhibitor rather than tamoxifen in premenopausal women receiving ovarian suppression reduces the risk of breast cancer recurrence. Longer follow-up is needed to assess any impact on breast cancer mortality.
- Published
- 2022
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