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Cognitive function in postmenopausal breast cancer patients one year after completing adjuvant endocrine therapy with letrozole and/or tamoxifen in the BIG 1-98 trial

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Abstract

Endocrine therapy for breast cancer may affect cognition. The purpose of this study was to examine whether cognitive function improves after cessation of adjuvant endocrine therapy. Change in cognitive function was assessed in 100 postmenopausal breast cancer patients in the BIG 1-98 trial, who were randomized to receive 5 years of adjuvant tamoxifen or letrozole alone or in sequence. Cognitive function was evaluated by computerized tests during the fifth year of trial treatment (Y5) and 1 year after treatment completion (Y6). Cognitive test scores were standardized according to age-specific norms and the change assessed using the Wilcoxon signed-rank test. There was significant improvement in the composite cognitive function score from Y5 to Y6 (median of change = 0.22, effect size = 0.53, P < 0.0001). This improvement was consistent in women taking either tamoxifen or letrozole at Y5 (P = 0.0006 and P = 0.0002, respectively). For postmenopausal patients who received either adjuvant letrozole or tamoxifen alone or in sequence, cognitive function improved after cessation of treatment.

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Acknowledgment

We thank the patients who participated in this trial, collaborators, and funding sources. Acknowledgment for respective individuals involved in the various groups is given in the Appendix. This work was supported by Novartis and coordinated by IBCSG. Support for the IBCSG: Swedish Cancer Society; The Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research (SAKK); National Cancer Institute at the National Institutes of Health (Grant number CA-75362); Cancer Research Switzerland/Oncosuisse; and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK);The Cancer Council Victoria, Dr. John Colebatch Clinical Research Fellowship (to K.A.P).

Conflict of interest

Financial disclosures: The substudy was funded by Novartis. Novartis contracted with the International Breast Cancer Study Group (IBCSG) for provision of services related to the conduct and management of the trial. Dr. Thürlimann owns stock in Novartis; Dr. Cardoso has received consulting and/or lecture fees from Novartis, Dr. Thompson and Dr. Goldhirsch have received honoraria from Novartis. The remaining authors have no conflicts to report.

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Correspondence to Jürg Bernhard.

Appendix

Appendix

BIG 1-98 collaborative group participants

Steering Committee : B. Thürlimann (Chair), S. Aebi, L. Blacher, A. S. Coates, T. Cufer, J. F. Forbes, R. D. Gelber, A. Giobbie-Hurder, A. Goldhirsch, A. Hiltbrunner, S. B. Holmberg, R. Maibach, A. Martoni, L. Mauriac, G. McGrogan, H. T. Mouridsen, R. Paridaens, D. Phuong, K. N. Price, M. Rabaglio, B.B. Rasmussen, M.M. Regan, A. Santoro, I. E. Smith, A. Wardley, G. Viale. Novartis: H. A. Chaudri-Ross, S. Segal, D. B. Evans, C. Sguotti

IBCSG Foundation Council (members from 1998 to 2008): S. Aebi, A. S. Coates, M. Colleoni, J. P. Collins, H. Cortés Funes, R. D. Gelber, A. Goldhirsch, M. Green, A. Hiltbrunner, S. B. Holmberg, P. Karlsson, I Kössler, I. Láng, J. Lindtner, F Paganetti M. de Stoppani, C.-M. Rudenstam, H.-J. Senn, R. Stahel, B. Thürlimann, A. Veronesi.

IBCSG Coordinating Center (Berne, Switzerland): A. Hiltbrunner (Director), M. Rabaglio, G. Egli, B. Ruepp, R. Maibach, N. Munarini, M. Castiglione.

Quality of Life Office (Berne, Switzerland): J Bernhard, K. Ribi, D. Gerber.

IBCSG Statistical Center (Boston, MA, USA): R. D. Gelber, K. N. Price, A. Giobbie-Hurder, Z. Sun, M.M. Regan, J. Aldridge, H. Huang.

IBCSG Data Management Center (FSTRF, Amherst, NY, USA): L. Blacher (Director of Data Management), T. Heckman Scolese (Coordinating Data Manager), J. Celano, S. Fischer, S. Lippert, L. Mundy, K. Scott, M. Scott, J. Swick, L. Uhteg, D. Weinbaum, C. Westby, T. Zielinski.

Breast international group (BIG)

International breast cancer study group (IBCSG)

Australian New Zealand Breast Cancer Trials Group (ANZ BCTG): R. D. Snyder, J. F. Forbes, F. Boyle; ANZ BCTG Operations Office (Newcastle, Australia): D. Lindsay, D. Preece, J. Cowell, D. Talbot, A. Whipp.

Australia: The Cancer Council Victoria, Melbourne: K. Wysman, S. Vickery, N. Ranieri, B. Gleeson, B. Scher, F. Abell, R. Basser, R. Bell, B. Brady, D. Blakey, P. Briggs, I. Burns, P. Campbell, M. Chao, J. Chirgwin, B. Chua, K. Clarke, J. Collins, R. De Boer, J. C. Din, R. Doig, A. Dowling, R. Drummond, N. Efe, S. T. Fan, M. Francis, P. Francis, V. Ganju, P. Gibbs, G. Goss, M. Green, P. Gregory, J. Griffiths, I. Haines, M. Henderson, R. Holmes, P. James, J. Kiffler, M. Lehman, M. Leyden, L. Lim, G. Lindeman, R. Lynch, B. Mann, J. McKendrick, S. McLachlan, R. McLennan, G. Mitchell, S. Mitra, C. Murphy, I. Parker, K. Phillips, I. Porter, G. Richardson, J. Scarlet, S. Sewak, J. Shapiro, R. Snyder, R. Stanley, C. Steer, D. Stoney, A. Strickland, G. Toner, C. Underhill, K. White, M. White, A. Wirth, S. Wong; W P Holman Clinic, Prince of Wales Hospital, Sydney: C. Lewis, A. Zaat, B. Brigham, D. Goldstein, M. Friedlander.

New Zealand: Auckland Hospital, V. J. Harvey, J. Proctor, J. Millet, B. Joppa, B. Evans, W. Jones, M. McCrystal, D. Porter, P. Thompson, M. Vaughan.

Italy: Istituto Europeo di Oncologia, Milano: M. Colleoni, G. Viale, P. Veronesi, G. Peruzzotti, L. Corsetto, R. Ghisini, G. Renne, A. Luini, L. Orlando, R. Torrisi, A. Rocca, T. De Pas, E. Munzone, V. Galimberti, S. Zurrida, M. Intra, F. Nolé, R. Orecchia, G. Martinelli, F. de Braud, A. Goldhirsch.

Switzerland: Swiss Group for Clinical Cancer Research (SAKK): University Hospital Basel, Basel: C. Rochlitz, E Müller, R. Herrmann, D. Oertli, E. Wight, H. Moch; Institute of Oncology of Southern Switzerland: Ospedale San Giovanni, Bellinzona: J. Bernier, L. Bronz, F. Cavalli, E. Gallerani, A. Richetti, A. Franzetti; Ospedale Regionale di Lugano (Civico & Italiano), Lugano: M. Conti-Beltraminelli, M. Ghielmini, T. Gyr, S. Mauri, P. C. Saletti; Ospedale Regionale Beata Vergine, Mendrisio: A. Goldhirsch, O. Pagani, R. Graffeo, M. Locatelli, S. Longhi, P.C. Rey, M. Ruggeri; Ospedale Regionale La Carità, Locarno: E. Zucca, D. Wyss; Istituto Cantonale di Patologia, Locarno: L. Mazzucchelli, E. Pedrinis, T. Rusca; Inselspital, Berne: S. Aebi, M. F. Fey, M. Castiglione, M. Rabaglio; Kantonsspital Olten, Olten: S. Aebi, M. F. Fey, M. Zuber, G. Beck; Kantonsspital St. Gallen, St. Gallen: B. Thürlimann, D. Köberle, F. Weisser, S. Mattmann, A. Müller, T. Cerny, B. Späti, M. Höfliger, G. Fürstenberger, B. Bolliger, C. Öhlschlegel, U. Lorenz, M. Bamert, J. Kehl-Blank, E. Vogel.

Belgium: Institut Jules Bordet, Bruxelles: J. M. Nogaret, V. Robberecht, V. Garreau, F. Cardoso.

United Kingdom: University of Dundee, Dundee: A. M. Thompson, B. Massie, J. A. Dewar.

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Phillips, KA., Aldridge, J., Ribi, K. et al. Cognitive function in postmenopausal breast cancer patients one year after completing adjuvant endocrine therapy with letrozole and/or tamoxifen in the BIG 1-98 trial. Breast Cancer Res Treat 126, 221–226 (2011). https://doi.org/10.1007/s10549-010-1235-y

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