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The advantage of letrozole over tamoxifen in the BIG 1-98 trial is consistent in younger postmenopausal women and in those with chemotherapy-induced menopause

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Abstract

Letrozole, an aromatase inhibitor, is ineffective in the presence of ovarian estrogen production. Two subpopulations of apparently postmenopausal women might derive reduced benefit from letrozole due to residual or returning ovarian activity: younger women (who have the potential for residual subclinical ovarian estrogen production), and those with chemotherapy-induced menopause who may experience return of ovarian function. In these situations tamoxifen may be preferable to an aromatase inhibitor. Among 4,922 patients allocated to the monotherapy arms (5 years of letrozole or tamoxifen) in the BIG 1-98 trial we identified two relevant subpopulations: patients with potential residual ovarian function, defined as having natural menopause, treated without adjuvant or neoadjuvant chemotherapy and age ≤55 years (n = 641); and those with chemotherapy-induced menopause (n = 105). Neither of the subpopulations examined showed treatment effects differing from the trial population as a whole (interaction P values are 0.23 and 0.62, respectively). Indeed, both among the 641 patients aged ≤55 years with natural menopause and no chemotherapy (HR 0.77 [0.51, 1.16]) and among the 105 patients with chemotherapy-induced menopause (HR 0.51 [0.19, 1.39]), the disease-free survival (DFS) point estimate favoring letrozole was marginally more beneficial than in the trial as a whole (HR 0.84 [0.74, 0.95]). Contrary to our initial concern, DFS results for young postmenopausal patients who did not receive chemotherapy and patients with chemotherapy-induced menopause parallel the letrozole benefit seen in the BIG 1-98 population as a whole. These data support the use of letrozole even in such patients.

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References

  1. Goldhirsch A, Ingle JN, Gelber RD, Coates AS, Thürlimann B, Senn HJ, Panel members (2009) Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann Oncol 20:1319–1329

    Article  PubMed  CAS  Google Scholar 

  2. Nelson LR, Bulun SE (2001) Estrogen production and action. J Am Acad Dermatol 45(Suppl 3):S116–S124

    Article  PubMed  CAS  Google Scholar 

  3. Lonning PE (1996) Pharmacology of new aromatase inhibitors. Breast 5:202–208

    Article  Google Scholar 

  4. Smith IE, Dowsett M, Yap Y-S, Walsh G, Lonning PE, Santen R (2006) Adjuvant aromatase inhibitors for early breast cancer after chemotherapy-induced amenorrhoea; caution and suggested guidelines. J Clin Oncol 24:2444–2447

    Article  PubMed  CAS  Google Scholar 

  5. Hargis JB, Nakajima ST (2006) Resumption of menses with initiation of letrozole after five years of amenorrhea on tamoxifen: caution needed when using tamoxifen followed by aromatase inhibitors. Cancer Invest 24:174–177

    Article  PubMed  CAS  Google Scholar 

  6. De Ziegler D, Mattenberger C, Luyet C, Romoscanu I, Irion NF, Bianchi-Demicheli F (2005) Clinical use of aromatase inhibitors (AI) in premenopausal women. J Steroid Biochem Mol Biol 95:121–127

    Article  PubMed  Google Scholar 

  7. Verberg MF, Macklon NS, Nargund G, Frydman R, Devroey P, Broekmans FJ, Fauser BC (2009) Mild ovarian stimulation for IVF. Hum Reprod Update 15:13–29

    Article  PubMed  CAS  Google Scholar 

  8. BIG 1-98 Collaborative Group (2005) A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 353:2747–2757

    Article  Google Scholar 

  9. Coates AS, Keshaviah A, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Colleoni M, Láng I, Del Mastro L, Smith I, Chirgwin J, Nogaret JM, Pienkowski T, Wardley A, Jacobsen EH, Price KN, Goldhirsch A (2007) Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol 25:486–492

    Article  PubMed  CAS  Google Scholar 

  10. BIG 1-98 Collaborative Group (2009) Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. N Engl J Med 361:766–776

    Article  Google Scholar 

  11. Colleoni M, Giobbie-Hurder A, Regan MM, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Láng I, Smith I, Chirgwin J, Pienkowski T, Wardley A, Price KN, Gelber RD, Coates AS, Goldhirsch A (2011) Analyses adjusting for selective crossover show improved overall survival with adjuvant letrozole compared with tamoxifen in the BIG 1-98 study. J Clin Oncol 29:1117–1124

    Article  PubMed  CAS  Google Scholar 

  12. Lazar AA, Cole BF, Bonetti M, Gelber RD (2010) Evaluation of treatment-effect heterogeneity using biomarkers measured on a continuous scale: subpopulation treatment effect pattern plot. J Clin Oncol 28:4539–4544

    Article  PubMed  Google Scholar 

  13. Viale G, Regan MM, Dell’Orto P, Mastropasqua MG, Maiorano E, Rasmussen BB, MacGrogan G, Forbes JF, Paridaens RJ, Colleoni M, Láng I, Thürlimann B, Mouridsen H, Mauriac L, Gelber RD, Price KN, Goldhirsch A, Gusterson BA, Coates AS, for the BIG 1-98 Collaborative and International Breast Cancer Study Groups (2011) Which patients benefit most from adjuvant aromatase inhibitors? Results using a composite measure of prognostic risk in the BIG 1-98 randomized trial. Ann Oncol. doi:10.1093/annonc/mdq738

  14. Abusief ME, Missmer SA, Ginsburg ES, Weeks JC, Partridge AH (2010) The effects of paclitaxel, dose density, and trastuzumab on treatment-related amenorrhea in premenopausal women with breast cancer. Cancer 116:791–798

    Article  PubMed  CAS  Google Scholar 

  15. Tham YL, Sexton K, Weiss H, Elledge R, Friedman LC, Kramer R (2007) The rates of chemotherapy-induced amenorrhea in patients treated with adjuvant doxorubicin and cyclophosphamide followed by a taxane. Am J Clin Oncol 30:126–132

    Article  PubMed  CAS  Google Scholar 

  16. Pérez-Fidalgo JA, Roselló S, García-Garré E, Jordá E, Martín-Martorell P, Bermejo B, Chirivella I, Guzman C, Lluch A (2010) Incidence of chemotherapy-induced amenorrhea in hormone-sensitive breast cancer patients: the impact of addition of taxanes to anthracycline-based regimens. Breast Cancer Res Treat 120:245–251

    Article  PubMed  Google Scholar 

  17. Berliere M, Dalenc F, Malingret N, Vindevogel A, Piette P, Roche H, Donnez J, Symann M, Kerger J, Machiels JP (2008) Incidence of reversible amenorrhea in women with breast cancer undergoing adjuvant anthracycline-based chemotherapy with or without docetaxel. BMC Cancer 8:56

    Article  PubMed  Google Scholar 

  18. Minisini AM, Menis J, Valent F, Andreetta C, Alessi B, Pascoletti G, Piga A, Fasola G, Puglisi F (2009) Determinants of recovery from amenorrhea in premenopausal breast cancer patients receiving adjuvant chemotherapy in the taxane era. Anticancer Drugs 20:503–507

    Article  PubMed  CAS  Google Scholar 

  19. Ortmann O, Cufer T, Dixon JM, Maass N, Marchetti P, Pagani O, Pronzato P, Semiglazov V, Spano JP, Vrdoljak E, Wildiers H (2009) Adjuvant endocrine therapy for perimenopausal women with early breast cancer. Breast 18:2–7

    Article  PubMed  Google Scholar 

  20. Pagani O, O’Neill A, Castiglione M, Gelber RD, Goldhirsch A, Rudenstam C-M, Lindtner J, Collins J, Crivellari D, Coates A, Cavalli F, Thürlimann B, Simoncini E, Fey M, Price K, Senn HJ (1998) Prognostic impact of amenorrhea after adjuvant chemotherapy in premenopausal breast cancer patients with axillary node involvement: results of the International Breast Cancer Study Group (IBCSG) Trial VI. Eur J Cancer 34:632–640

    Article  PubMed  CAS  Google Scholar 

  21. Swain SM, Land SR, Ritter MW, Costantino JP, Cecchini RS, Mamounas EP, Wolmark N, Ganz PA (2009) Amenorrhea in premenopausal women on the doxorubicin-and-cyclophosphamide-followed-by-docetaxel arm of NSABP B-30 trial. Breast Cancer Res Treat 113:315–320

    Article  PubMed  CAS  Google Scholar 

  22. Ganz PA, Land SR, Geyer CE, Cecchini RS, Costantino JP, Pajon ER, Fehrenbacher L, Atkins JN, Polikoff JA, Vogel VG, Erban JK, Livingston RB, Perez EA, Mamounas EP, Wolmark N, Swain SM (2011) Menstrual history and quality-of-life outcomes in women with node-positive breast cancer treated with adjuvant therapy on the NSABP B-30 trial. J Clin Oncol 29:1110–1116

    Article  PubMed  Google Scholar 

  23. Amir E, Seruga B, Freedman O, Clemons M (2009) Amenorrhoea, menopause, and endocrine therapy for breast cancer. BMJ 339:b4261

    Article  PubMed  Google Scholar 

  24. Clemons M, Simmons C (2007) Identifying menopause in breast cancer patients: considerations and implications. Breast Cancer Res Treat 104:115–120

    Article  PubMed  CAS  Google Scholar 

  25. Chirgwin JH, Lewis J, Woodfield R, Eden J, Davis SR, de Boer R, for the ENHANCE Consultative Group, Australia (2009) Menopause surveillance recommendations for patients with endocrine-responsive breast cancer. Cancer Res 69(2 Suppl):Abstract nr 1148

    Google Scholar 

  26. Goss PE, Ingle JN, Martino S, Robert N, Muss H, Shepherd L, Pritchard KI, Livingston RB, Davidson N, Perez EA, Cameron D, Whelan T, Palmer M, Tu D (2009) Outcomes of women who were premenopausal at diagnosis of early stage breast cancer in the NCIC CTG MA17 trial. Cancer Res 69(24 Suppl):Abstract nr 13

    Google Scholar 

Download references

Acknowledgment

We thank the patients, physicians, nurses, and data managers who participated in the BIG 1-98 clinical trial. The BIG 1-98 trial was financed 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 Grant CA-75362, Cancer Research Switzerland/Oncosuisse, and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK). Clinicaltrials.gov ID = NCT00004205.

Conflict of interest

Jacquie Chirgwin: Advisory Board (Novartis); Beat Thürlimann: Consultant/advisor: Novartis, Astra Zeneca; Hervé Bonnefoi: Renumeration Novartis, Astra Zeneca, Pfizer; Aron Goldhirsch: Speakers honoraria, Novartis. Zhuoxin Sun, Ian Smith, Karen N. Price, Bent Ejlertsen, Meredith M. Regan, Alan S. Coates: No conflicts

Author information

Authors and Affiliations

  1. Australian New Zealand Breast Cancer Trials Group, Newcastle, NSW, Australia

    Jacquie Chirgwin

  2. Box Hill and Maroondah Hospitals, Monash University, Melbourne, VIC, Australia

    Jacquie Chirgwin

  3. International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute, Boston, MA, USA

    Zhuoxin Sun

  4. The Royal Marsden Hospital, Institute of Cancer Research, London, United Kingdom

    Ian Smith

  5. International Breast Cancer Study Group Statistical Center, Frontier Science and Technology Research Foundation, Boston, MA, USA

    Karen N. Price

  6. Breast Center, Kantonsspital St. Gallen, St. Gallen, Switzerland

    Beat Thürlimann

  7. Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland

    Beat Thürlimann

  8. Danish Breast Cancer Cooperative Group (DBCG), Rigshospitalet, Copenhagen, Denmark

    Bent Ejlertsen

  9. Medical Oncology, Institut Bergonié, Université de Bordeaux, INSERM U916, FNCLCC (Unicancer), Bordeaux, France

    Hervé Bonnefoi

  10. International Breast Cancer Study Group (IBCSG) Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard School of Public Health and Harvard Medical School, Boston, MA, USA

    Meredith M. Regan

  11. European Institute of Oncology, Milan, Italy

    Aron Goldhirsch

  12. Swiss Center for Breast Health, Sant’Anna Clinics, Lugano-Sorengo, Switzerland

    Aron Goldhirsch

  13. International Breast Cancer Study Group, University of Sydney School of Public Health, Sydney, NSW, Australia

    Alan S. Coates

Authors
  1. Jacquie Chirgwin
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  2. Zhuoxin Sun
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  3. Ian Smith
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Consortia

for the BIG 1-98 Collaborative and International Breast Cancer Study Groups

Corresponding author

Correspondence to Jacquie Chirgwin.

Additional information

The participants of the BIG 1-98 Collaborative and International Breast Cancer Study Groups are given in Appendix.

Appendix

Appendix

BIG 1-98 Collaborative Group Participants

Steering Committee: B. Thürlimann (Chair), S. Aebi, L. Blacher, H. Bonnefoi, A. S. Coates, T. Cufer, B. Ejlertsen, J. F. Forbes, R. D. Gelber, A. Giobbie-Hurder, A. Goldhirsch, A. Hiltbrunner, S. B. Holmberg, R. Maibach, A. Martoni, L. Mauriac, G. MacGrogan, 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.

IBCSG Foundation Council (members from 1998 to 2010): 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.

Coordinating Center (Berne, Switzerland): M. Castiglione (Chief Executive Officer 1998–2007), A. Hiltbrunner (Director), M. Rabaglio, G. Egli, H. Hawle, B. Cliffe, S. Ribeli-Hofmann, F. Munarini, R. Kammler, R. Studer, B. Ruepp, R. Maibach, N. Munarini.

Statistical Center (Dana-Farber Cancer Institute, Boston, MA, USA): R. D. Gelber (Director), M. M. Regan (Group Statistician), K. N. Price (Director of Scientific Administration), A. Giobbie-Hurder (Trial Statistician), A. Keshaviah, H. Litman, Z. Sun, H. Huang, L. J. Somos, B. Timmers, L. Nickerson.

Data Management Center (Frontier Science & Technology Research Foundation, Amherst, NY, USA): L. Blacher (Director of Data Management), T. Heckman Scolese (Coordinating Data Manager), M. Belisle, M. Caporale, J. Celano, L. Dalfonso, L. Dooley, S. Fischer, K. Galloway, J. Gould, R. Hinkle, M. Holody, G. Jones, R. Krall, S. Lippert, J. Meshulam, L. Mundy, A. Pavlov-Shapiro, K. Scott, M. Scott, S. Shepard, J. Swick, L. Uhteg, D. Weinbaum, C. Westby, T. Zielinski.

Central Pathology Review Office (University of Glasgow, Glasgow, UK): B. A. Gusterson, E. Mallon; (European Institute of Oncology, Division of Pathology, Milano, Italy): G. Viale, P. Dell’Orto, M. Mastropasqua, B. Del Curto.

Study Support (Novartis Corp. Basel, Switzerland): E. Waldie, I. van Hoomissen, M. De Smet, U. Trostmann, W. Schmidt, A. Bolton, W. Hackl.

Breast International Group (BIG)

International Breast Cancer Study Group (IBCSG)

Australian New Zealand Breast Cancer Trials Group (ANZ BCTG): R. D. Snyder, J. Chirgwin, J. F. Forbes, A. S. Coates, F. Boyle, D. Lindsay, D. Preece, J. Cowell, D. Talbot, A. Whipp.

Australia: The Cancer Council Victoria, Melbourne, VIC: 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, Launceston General Hospital, Launceston, Tasmania: D. Byram, I. Byard; Liverpool Hospital, Sydney, NSW: S. Della-Fiorentina, A. Goldrick, E. Hovey, E. Moylan, E. Segelov; Mount Hospital, Perth, WA: A. Chan, M. Buck, D. Hastrich, D. Ingram, G. Van Hazel, P. Willsher; Nepean Cancer Care Centre, Sydney, NSW: N. Wilcken, C. Crombie; Calvary Mater Newcastle, Newcastle, NSW: J. F. Forbes, F. Abell, S. Ackland, A. Bonaventura, S. Cox, J. Denham, R. Gourlay, D. Jackson, R. Sillar, J. Stewart; Prince of Wales Hospital, Sydney, NSW: C. Lewis, B. Brigham, D. Goldstein, M. Friedlander; Princess Alexandra Hospital, Woollongabba, QLD: E. Walpole, D. Thompson; Royal Adelaide Hospital, Adelaide, SA: P. G. Gill, M. Bochner, J. Coventry, J. Kollias, P. Malycha, I. Olver; Royal Brisbane and Women’s Hospital, Brisbane, QLD: M. Colosimo, R. Cheuk, L. Kenny, N. McCarthy, D. Wyld; Royal Hobart Hospital, Hobart, Tasmania: R. Young, R. Harrup, R. Kimber, R. Lowenthal; Royal Perth Hospital, Perth, WA: J. Trotter, E. Bayliss, A. Chan, D. Ransom; Sir Charles Gairdner Hospital, Perth, WA: M. Byrne, M. Buck, J. Dewar, A. Nowak, A. Powell, G. Van Hazel; Toowoomba Hospital, Toowoomba, QLD: E. A. Abdi, R. Brodribb, Z. Volobueva; Westmead Hospital, Sydney, NSW: P. Harnett, V. Ahern, H. Gurney, N. Wilcken.

New Zealand: Auckland Hospital, Auckland: V. J. Harvey, B. Evans, W. Jones, M. McCrystal, D. Porter, P. Thompson, M. Vaughan; Christchurch Hospital, Christchurch: D. Gibbs, C. Atkinson, R. Burcombe, B. Fitzharris, B. Hickey, M. Jeffery, B. Robinson; Dunedin Hospital, Dunedin: B. McLaren, S. Costello, J. North, D. Perez; Waikato Hospital, Hamilton: I. D. Campbell, L. Gilbert, R. Gannaway, M. Jameson, I. Kennedy, J. Long, G. Round, L. Spellman, D. Whittle, D. Woolerton.

Brazil: Hospital de Clinicas de Porto Alegre, Porto Alegre: C. Menke, J. Biazús, R. Cericatto, J. Cavalheiro, N. Xavier, A. Bittelbrunn, E. Rabin.

Chile: Chilean Cooperative Group for Oncologic Research, GOCCHI: J. Gutiérrez (Chairman), R. Arriagada (Scientific Adviser), L. Bronfman (Principal Investigator), M. Zuñiga (Data Manager); Clinica Las Condes, Santiago: J. Gutiérrez, J. C. Acevedo, S. Torres, A. León, E. Salazar; Hospital DIPRECA, Las Condes, Santiago: L. Soto Diaz, R. Duval, N. Oddeshede, M. C. Venti; Hospital San Juan de Dios, Santiago: K. Peña, L. Puente, V. Maidana; IRAM/Instituto de Radiomedicina, Vitacura, Santiago: R. Baeza, R. Arriagada, P. Olfos, J. Solé, E. Vinés, C. Mariani.

Hungary: National Institute of Oncology, Budapest: I. Láng, E. Hitre, E. Szabó, Z. Horváth, E. Ganofszky, E. Juhos.

Italy: Centro di Riferimento Oncologico, Aviano: A. Veronesi, D. Crivellari, M. D. Magri, A. Buonadonna, F. Coran, E. Borsatti, E. Candiani, S. Massarut, M. Roncadin, M. Arcicasa, A. Carbone, T. Perin, A. Gloghini; Ospedali Riuniti di Bergamo, Bergamo: C. Tondini, R. Labianca, P. Poletti, A. Bettini; Ospedale degli Infermi, Biella: M. Clerico, M. Vincenti, A. Malossi, E. Seles, E. Perfetti, B. Sartorello; Spedali Civili, Brescia: E. Simoncini, G. Marini, P. Marpicati, R. Farfaglia, A. M. Bianchi, P. Grigolato, L. Lucini, P. Frata, A. Huscher, E. Micheletti, C. Fogazzi; U. O. Medicina Oncologica, Ospedale Capri, Ospedale Mirandola: F. Artioli, K. Cagossi, L. Scaltriti, E. Bandieri, L. Botticelli, G. Giovanardi; Ospedale di Cattolica “Cervesi”, Cattolica: A. Ravaioli, E. Pasquini, B. Rudnas; Ospedale Civile, Gorizia: L. Foghin; Ospedale “A. Manzoni” Lecco, Lecco: M. Visini, L. Zavallone, G. Ucci; 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; Ospedale Infermi, Rimini: A. Ravaioli, L. Gianni.

Peru: Instituto de Enfermedades Neoplásicas, Lima: H. Gome.

Slovenia: Institute of Oncology, Ljubljana: T. Cufer, B. Pajk, J. Cervek.

South Africa: Groote Schuur Hospital and University of Cape Town, Cape Town: I. D. Werner, E. Murray, D. Govender, S. Dalvie, T. Erasmus, B. Robertson, B. Read, E. Nel, J. Toop, N. Nedeva, E. Panieri; Sandton Oncology Centre, Johannesburg: D. Vorobiof, M. Chasen, G. McMichael, C. Mohammed. Local funding provided by the Cancer Association of South Africa.

Sweden: West Swedish Breast Cancer Study Group: S. B. Holmberg; Sahlgrenska U Hospital, Moelndal: S. B. Holmberg, J. Mattsson; Boras Hospital, Boras; Karlstads Hospital, Karlstads: H. Sellström; Kungalvs Hospital, Kungalvs: B. Lindberg.

Switzerland: Swiss Group for Clinical Cancer Research (SAKK): A. Goldhirsch (up to January 2004), R. Herrmann (June 2004 to June 2010), B. Thürlimann (from July 2010): Kantonsspital Aarau, Zentrum f. Onkologie, Aarau: A. Schönenberger, W. Mingrone, Ch. Honegger, E. Bärtschi, M. Neter, M. Rederer, G. Schär; University Hospital Basel, Basel: C. Rochlitz, 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; Bürgerspital, Solothurn: S. Aebi, M. F. Fey, R. Schönenberger; Spital Thun-Simmental AG Thun: J.M. Lüthi, D. Rauch; Hôpital Cantonal Universitaire HCUG, Geneva: H. Bonnefoi; Rätisches Kantons- und Regionalspital, Chur: F. Egli, R. Steiner, P. Fehr; Centre Pluridisciplinaire d’Oncologie, Lausanne: L. Perey, P. de Grandi, W. Jeanneret, S. Leyvraz, J.-F. Delaloye; Kantonsspital St. Gallen, St. Gallen: B. Thürlimann, D. Köberle, T. Ruhstaller, 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; Kantonales Spital Herisau, Herisau: B. Thürlimann, D. Hess, I. Senn, D. Köberle, A. Ehrsam, C. Nauer, C. Öhlschlegel, J. Kehl-Blank, E. Vogel; Stadtspital Triemli, Zürich: L. Widmer, M. Häfner; Universitätsspital Zürich, Zürich: B. C. Pestalozzi, M. Fehr, R. Caduff, Z. Varga, R. Trüb, D. Fink.

Swiss Private MDs: Private Praxis, Zürich: B. A. Bättig; Sonnenhof-Klinik Engeried, Berne: K. Buser; Frauenklinik Limmattalspital, Schlieren: N. Bürki; Private Praxis, Birsfelden: A. Dieterle; Private Praxis, Biel: L. Hasler; Private Praxis, Baar: M. Mannhart-Harms; Brust-Zentrum, Zürich: C. Rageth; Private Praxis, Berne: J. Richner; Private Praxis, Bellinzona: V. Spataro; Private Praxis, Winterthur: M. Umbricht.

United Kingdom: King’s College Hospital/Breast Unit, London: P. Ellis, S. Harris, N. Akbar, H. McVicars, C. Lees, R. Raman, G. Crane.

Danish Group (DBCG)

H. T. Mouridsen; Rigshospitalet, Copenhagen: H. T. Mouridsen; Vejle Hospital, Vejle: E. Jakobsen; Odense University Hospital, Odense: S. Cold; KAS Herlev/Herlev University Hospital, Herlev: C. Kamby; Aalborg Sygehus Syd, Aalborg: M. Ewertz; Hilleroed Hospital, Hilleroed: P. M. Vestlev; Aarhus University Hospital, Aarhus: J. Andersen; Roskilde County Hospital, Roskilde: P. Grundtvig; Esbjerg Central Hospital, Esbjerg: E. Sandberg; Naestved Central Hospital, Naestved: P. Philip; Soenderborg Sygehus, Soenderborg: E. L. Madsen; Herning Central Hospital, Herning: K. A. Moeller; Viborg Sygehus, Viborg: V. Haahr; Landspitali University Hospital, Reykjavik, Iceland: J. Johansson.

French Group (FNCLCC)

Institut Bergonié, Bordeaux: L. Mauriac, M. Debled, P. Campo; Centre Hospitalier de la Côte Basque, Bayonne: D. Larregain-Fournier, S. Remy; Centre Jean Perrin, Clermont-Ferrand: H. Auvray; Centre Georges François Leclerc, Dijon: C. De Gislain, F. Delille, M.-C. Porteret; Centre Oscar Lambret, Lille: V. Servent, M. Chapoutier; CHRU, Limoges: N. Tubiana-Mathieu, S. Lavau-Denes, P. Bosc; Centre Léon Bérard, Lyon: J. P. Guastalla, Th. Bachelot, C. Arbault; Centre Hospitalier Meaux, Meaux: G. Netter-Pinon; C.H.G. André Boulloche, Montbéliard: V. Perrin, A. Monnier, Y. Hammoud; Centre Paul Lamarque, Montpellier: G. Romieu, L. Culine, V. Pinosa; Clinique Francheville, Périgueux: L. Cany, C. Maguire; Hôpital de la Milétrie, Poitiers: A. Daban, M. Le Saux, C. Grandon; Centre Eugène Marquis, Rennes: P. Kerbrat, C. Catheline; Centre Henri Becquerel, Rouen: C. Veyret, E. Jugieau, V. Talon; Centre René Gauducheau, Saint-Herblain: A. Le Mevel, S. Maury; Centre Claudius Régaud, Toulouse: L. Gladieff, N. Lignon.

North Yorkshire Group

D. Dodwell; Harrogate District Hospital, Harrogate, North Yorkshire: D. Dodwell; Huddersfield Royal Infirmary, Huddersfield: J. Joffe; Castlehill Hospital, Hull: P. Drew; Airedale General Hospital, Keighley: W. Yorkshire: A. Nejim; Leeds General Infirmary, Leeds: D. Dodwell, K. Horgan; St. James’s University Hospital, Leeds: M. Lansdown, T. Perren; Weston Park Hospital, Sheffield: R. E. Coleman.

Independent Centers/Groups

Argentina: Centro Oncológico Confidence, Buenos Aires: D. Campos; Hospital Allemán, Buenos Aires: F. Cóppola; Hospital Británico, Buenos Aires: J. Martinez; Hospital Evita, Buenos Aires: M. Freue; Hospital Posadas, Buenos Aires: C. Wainstein; Hospital Zubizarreta, Buenos Aires: A. Zori Comba; Instituto Dr. Estevez, Buenos Aires: E. Cazap; Instituto Oncológico Dr. Angel H. Roffo, Buenos Aires: E. Mickiewicz; Sanatorio Municipal Julio A. Mendez, Buenos Aires: L. Balbiani; Centro Privado de Ginecología, Córdoba: A. Osuna; Hospital Privado de Córdoba, Córdoba: E. Palazzo; Instituto Modelo de Ginecología y Obstetricia, Córdoba: M. de Romedis; Fundación Mainetti-Centro Oncológico de Excelencia, La Pllata: S. Cagnolati; Hospital Privado de la Comunidad, Mar del Plata: C. A. Delfino, G. Caccia; Escuela de Medicina Nuclear (COIR), Mendoza: R. L. de Angelis; Centro Oncológico de Rosario, Rosario: L. Fein, R. Sala; Hospital Provincial de Rosario, Rosario: C. Nassurdi, A. Colombo Berra; Clínica Especializada ISIS, Santa Fe: R. Viroglio, C. Blajman; Hospital Regional de Concepción, Tucumán: H. Requejo; Instituto de Maternidad y Ginecología Nuestra Señoras de las Mercedes, Tucumán: L. Silberman.

Australia: Flinders Medical Centre, Adelaide, SA: S. Birrell, M. Eaton, C. Hoffman; Queen Elizabeth Hospital, Adelaide, SA: V. Humeniuk; The Canberra Hospital, Canberra, ACT; P. Craft, R. Stuart-Harris, D. Yip; The Geelong Hospital, Geelong, VIC: R. Bell, F. Abell, M. Francis, J. Kiffer, R. Lynch, R. McLennan, K. White; Royal Melbourne Hospital, Melbourne, VIC: M. Green, R. Basser, J. Collins, R. De Boer, J. C. Din, N. Efe, S. T. Fan, G. Lindeman, S. Wong; Western General Hospital, Melbourne, VIC: M. Green, R. Basser, J. Collins, R. De Boer, J. C. Din, N. Efe, S. T. Fan, G. Lindeman, S. Wong; Newcastle Mater Hospital, Newcastle, NSW: J. Stewart, F. Abell, S. Ackland, A. Bonaventura; Royal Perth Hospital, Perth, WA: J. Trotter, E. Bayliss, A. Chan, D. Ransom, A. Redfern; St. George Hospital, Sydney, NSW: P. de Souza, M. Links; St. Vincent’s Hospital, Sydney, NSW: D. Dalley, J. Grygiel, R. Ward; Murray Valley Private Hospital, Wodonga, VIC: C. Underhill, K. Clarke, C. Steer; Princess Alexandra Hospital, Woolloongabba, QLD: E. Walpole, D. Thompson.

Belgium: Institut Jules Bordet, Bruxelles: J. M. Nogaret; University Hospitals Leuven, Leuven: M. R. Christiaens, P. Neven, R. Paridaens, A. Smeets, I. Vergote, C. Weltens, H. Wildiers; Les Cliniques Saint-Joseph ASBL, Liège: C. Focan; Clinique du Parc Léopold, Bruxelles: L. Marcelis; C. H. Etterbeek—Ixelles, Bruxelles: J. P. Kains; Service d’Oncologie Clinique Notre-Dame, Charleroi: J.-L. Canon; C. H. U. André Vèsale, Montigny-Le Tilleul: D. Brohèe.

Canada: Cambridge Memorial Hospital, Cambridge: J. Gowing; CHUM Campus Notre-Dame, Montreal: L. Yelle; Hôpital Maisonneuve-Rosemont, Montreal: P. Dubé.

Chile: Fundacion Lopez Perez, Santiago: C. Vogel; Hospital Carlos Van Buren, Valparaiso: M. León Prieto.

Czech Republic: Institute of Oncology, Brno: K. Petrakova, M. Palacova, R. Demlova; Dept. of Clinical and Radiation Oncology, Ceske Budejovice: H. Siffnerova, J. Fischer, I. Bustova; Centre of Breast Diseases, Prague: H. Kankova, M. Pintova; Institute of Radiation Oncology, Prague: P. Vitek; University Hospital, Prague: J. Abrahamova, D. Kordikova; University Hospital, Prague: L. Petruzelka, E. Sedlackova, H. Honova.

Germany: Onkologische Gemeinschaftspraxis, Augsburg: B. Heinrich; Zentralklinikum/Frauenklinik, Augsburg: A. Wischnik; Universitätsklinikum Essen, Essen: C. Oberhoff, A. E. Schindler; Universitäts-Frauenklinik d. JLU Giessen, Giessen: K. Münstedt; Onkologische Gemeinschaftspraxis, Göttingen: D. Meyer; Martin-Luther-Universität Halle-Wittenberg, Halle: R. Grosse, H. Kölbl; Universitätskliniken des Saarlandes, Homburg: W. Schmidt, D. Mink; Universitäts-Frauenklinik und Poliklinik Universitätskrankenhaus Eppendorf, Hamburg: F. Jänicke; Kliniken d. Med. Hochschule, Frauenklinik, Hannover: H. J. Lück; Krankenanstalt Mutterhaus der Borromäerinnen, Trier: W. Dornoff; Gynäkologische Abteilung des St. Josefshospital, Wiesbaden: G. Hoffmann; Gynäkologische Abteilung d. Marienhospitals, Universität Witten-Herdecke, Witten: J. Hackmann, W. Bader.

Hungary: SZOTE Onkoterápiás Klinika, Szeged: Z. Kahan; BM Központi Kórház, Budapest: G. Pajkos, K. Kristo; SOTE Radiológiai és Onkoterápiás Klinika, Budapest: M. Dank; Uzsoki Utcai Kórház, Budapest: T. Nagykalnai, L. Landherr; Almási Balogh Pál Kórház, Ózd: E. Kner; Területi Kórház Onkologia, Szentes: M. Kispál; Szent Borbála Kórház, Megyei Onkológiai Gondozó, Tatabánya: Á. Dani.

Italy: Policlinico S. Orsola-Malpighi, Bologna: A. Martoni, C. Zamagni, S. Giaquinta, E. Piana; Ospedale S. Croce, Fano: R. Mattioli, L. Imperatori; Istituto Clinica Humanitas, Milan/Rozzano: A. Santoro, C. Carnaghi, L. Rimassa; Azienda Ospedaliera San Filippo Neri, Rome: G. Gasparini, G. Sciarretta, A. Morabito; Az. Ospedaliera Treviglio-Caravaggio, Treviglio: S. Barni, M. Cazzaniga, M. Cabiddu; Policlinico Universitario (PUDG), Udine: F. Puglisi; Ospedale di Torrette, Ancona: R. Cellerino, S. Antognoli, F. Freddari; Universitiy of Cagliari, Policlinico Universitario, Cagliari: G. Mantovani, E. Massa, G. Astara; Ospedale Civile Feltre, Feltre: R. Segati; Istituto Nazionali Ricerca Cancro, Genova: R. Rosso, L. Del Mastro, M. Venturini, C. Bighin; Istituto Nazionale dei Tumori, Milano: E. Bajetta, N. Zilembo, D. Paleari, G. Procopio; Azienda Ospedaliera di Parma, Parma: S. Salvagni, M. A. Perrone, V. Franciosi; Azienda Ospedaliera “S. Salvatore”, Pesaro: G. Catalano, S. Luzi Fedeli; Azienda Ospedaliera “Ospedale di Circolo e Fondazione Macchi”, Varese: G. Pinotti, G. Giardina, I. Vallini; Universitiy of Cagliari, Policlinico Universitario, Cagliari: B. Massidda, M. T. Ionta, M. C. Deidda; Ospedale Maggiore, Lodi: G. Nalli, G. Sita; Policlinico Universitario, Palermo: I. Carreca, S. Cucciarré, D. Burgio; Ospedale Civile dello Spirito Santo, Pescara: M. Lombardo, G. Pandoli, P. Di Stefano; Azienda Ospedaliera Santa Maria Nuova, Reggio Emilia: C. Boni, G. Bisagni, M. C. Banzi, P. Linarello; Azienda Ospedaliera Desenzano del Garda, Manerbio: G. Colosini, A. Spasiano, A. Caldonazzo; Ospedale Civile ASL 20, Tortona: M. G. Pacquola.

Netherlands: Ziekenhuis Leyenburg, Den Haag: H. P. Sleeboom; Catharina Ziekenhuis, Eindhoven: H. J. T. Rutten; St. Anna Ziekenhuis, Geldrop: E. J. T. Luiten; Tweesteden Ziekenhuis, Tilburg: H. Th. J. Roerdink; Maxima Medisch Centrum, Veldhoven: R. H. M. Roumen.

New Zealand: Dunedin Hospital, Dunedin: B. McLaren, S. Costello, J. North, D. Perez, K., Bayston, M. Pfieffer; Waikato Hospital, Hamilton: I. Kennedy, I. D. Campbell, L. Gilbert, R. Gannaway, M. Jameson, J. Long, G. Round, L. Spellman, D. Whittle, D. Woolerton.

Poland: Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk: J. Jassem, M. Welnicka-Jaskiewicz, E. Senkus-Konefka, K. Matuszewska; Rydygier’s Memorial Hospital, Krakow-Nova Huta: P. Koralewski, J. Pernal; Klinika Nowotworów Piersi i, Chirurgii Rekonstrukcyjnej-Warszawa, Warszawa: T. Pienkowski, E. Brewczynska, B. Bauer-Kosinska, R. Sienkiewicz-Kozlowska, A. Jagiello-Gruszfeld, K. Sudol; Centrum Onkologii w Bydgoszczy, Oddzial Onkologii Klinicznej, Bydgoszcz: J. Tujakowski, B. Zurawski; Collegium Medicum Jagiellonian University, Krakow: J. Pawlega, E. Jablonska, A. Zygulska; Oddzial Kliniczny Onkologiczny, Centralnego Szpitala Klinicznego Wojskowej, Akademii Medycznej-Warszawa, Warszawa: M. Górnasiowa; Dolnoslaskie Centrum Onkologii, Wroclaw: E. Filypczyk-Cisarz, K. Pajak.

Portugal: Hospital de S. João, Porto: M. Damasceno; Instituto Português de Oncologia de Coimbra, Coimbra: J. Q. Albano; Hospital de Santa Maria, Lisboa: B. da Costa, L. Costa; Instituto Português de Oncologia de Lisboa, Lisboa: A. Henriques, H. Amaral; Hospital Geral de Santo António, Porto: F. Marques.

Russia: Cancer Research Centre, Moscow: D. V. Komov, S. B. Polikarpova; Moscow Municipal Hospital No. 62, Moscow: A. N. Makhson, N. V. Zabaznyi; Moscow Research Institute of Diagnostics and Surgery, Moscow: E. K. Vozny, N. Y. Dobrovolskaya, S. Bolshakova, O. V. Yurgina; N. M. Emmanuel Institute of Biochemical Physics, Moscow: D. B. Korman, I. A. Maslova; N.N. Petrov Research Institute of Oncology, St. Petersburg: V. Semiglazov, V. Ivanov; Saint-Petersburg City Oncological Dispensary, St. Petersburg: G. Manikhas, G. Dolmatov.

South Africa: Mamma Clinic, Tygerberg Hospital, Cape Town: J. Apffelstaedt; Southern Cross Hospital, Cape Town: D. Eedes; Pretoria Academic Hospital, Pretoria: C. Slabber; Pretoria East Hospital, Pretoria: M. A. Coccia-Portugal; Eastern Cape Oncology Centre, Port Elizabeth: K. Maart.

Spain: Hospital Ruber Internacional, Madrid: J. E. Alés Martinez, P. Aramburo, R. Sánchez; Hospital Son Dureta, Palma del Mallorca: J. Rifa, J. Martin; Centro Oncológico Integral de Madrid (CONIM), Madrid: R. Pérez-Carrión, J. L. González Larriba, A. Cubillo; Hospital Universitario San Carlos, Madrid: M. M. Jiménez, A. Casado; Hospital Central de Asturias, Oviedo: J. Fra, J. M. Vieitez, E. Esteban, A. J. Lacave.

Switzerland: Universitätsfrauenklinik, Basel: E. Wight, S. Bartens, R. Decio, U. Güth; Klinik am Park, Zürich: U. Breitenstein.

Turkey: Ankara University Ibni Sina Hospital, Ankara: F. Icli, D. Dincol; Hacettepe University Oncology Institute, Ankara: E. Baltali, Y. Ozisik; Istanbul University Oncology Institute, Istanbul: E. Topuz, M. Basaran, A. Aydiner; Ege University Medical School, Izmir: E. Ozdedeli; 9 Eylul University Medical School, Izmir: O. Harmancioglu, A. U. Yilmaz.

United Kingdom: The Royal Marsden Hospital, London, Royal Marsden NHS Trust, Surrey: I. E. Smith; University of Dundee, Dundee: A. M. Thompson; Christie Hospital NHS Trust, South Manchester University Hospital Trust, Manchester: A. Wardley; Royal Bournemouth Hospital, Bournemouth: T. Hickish; North Middlesex Hospital, London: F. Neave.

Uruguay: Hospital de Clinicas Dr. Manuel Quintela, Montevideo, Uruguay: G. Sabini.

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Chirgwin, J., Sun, Z., Smith, I. et al. The advantage of letrozole over tamoxifen in the BIG 1-98 trial is consistent in younger postmenopausal women and in those with chemotherapy-induced menopause. Breast Cancer Res Treat 131, 295–306 (2012). https://doi.org/10.1007/s10549-011-1741-6

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