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N Engl J Med. 2018 Jul 12;379(2):122-137. doi: 10.1056/NEJMoa1803164. Epub 2018 Jun 4.

Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer.

Collaborators (405)

Blacher L, Hiltbrunner A, Kammler R, Loibl S, Martinez J, Scott K, Shaw H, Torrisi R, Tryfonidis K, Viale G, Katkade V, Amauri Soares J, Boyle F, Jerusalem G, Stahl R, Aebi S, DiLeo A, Karlsson P, Kössler I, Fournarakou S, Roschitzki H, Roux S, Bonetti M, Feng Y, Giobbie-Hurder A, Gray K, Huang H, Luo W, Mahoney C, Price K, Zickl L, Blackwell M, Cesario A, Dickinson A, Donahue K, Greco M, Gonzalez P, Heckman-Scolese T, Hecker R, Hinkle R, Kalera M, Lupejkis K, Mora de Karausch A, Palermo V, Swick-Jemison J, Andrighetto S, Biasi O, Dell’Orto P, Russo L, Bernhard J, Ribi K, Piccart-Gebhart M, Abrams J, Mooney M, Zujewski JA, Hering M, Pandit S, Santos O, Frankel W, Rohrer D, Jewell S, McCart LM, Jewell R, Savoie J, Grant C, Cisar L, Katkade V, Francis P, Laycock I, Stewart J, Chirgwin J, van der Westhuizen A, Briscoe K, Redfern A, Koczwara B, Gauden S, Moylan E, Della-Fiorentina S, Nottage M, Boadle D, Snyder R, Sardelic F, Abdi E, Chipman M, Gombos A, Barbeaux A, Salmon JP, Neven P, Azim H, Parmar V, Gianni L, Simoncini E, Fabrizio A, Graiff C, Santoro A, Gomez H, Skof E, Vorobiof D, Linderholm B, Zaman K, Rabaglio M, Buser K, von Moos R, Rochlitz C, Rauch D, Gabriel N, Reißmüller K, Von Minckwitz G, Augustin D, Tomé O, Lorenz-Salehi F, Hahn A, Lüdders D, Bliss J, Gillman A, Atkins N, Earl H, McAdam K, Carey L, Partridge A, O’Regan RM, Gluck S, Pritchard KI, Whelan T, Gelmon K, Webster M, Wolmark N, Mamounas T, White J, Swain S, Hortobagyi GN, Gralow JR, Scott AF, Tonkin KS, Potvin KR, Tozer RG, Gapski JA, Prady C, Salim M, Sami A, Whitlock P, Roy JA, Hamm C, Freimann JH, Mortimer JE, Rugo HS, Ryan CJ, Parker BA, Elias AD, Tannenbaum S, Van Echo DC, Perez E, Wender DB, Walters TA, Merkel DE, Zaren HA, Rose CG, Kindler HL, Ansari RH, Nattam SR, Vogel SJ, McIntyre AP, Erban JK, Krag KJ, Hendricks CB, Rak Tkaczuk KH, Riseberg DA, Zakalik D, Flynn PJ, Schneider DJ, Naughton MJ, Stephenson WT, Marchello BT, Feldmann JE, Messino MJ, Hetzel DJ, Wos EJ, Sen K, Reed EC, Bonnem EM, Blom DH, Entmacher MS, Tiersten AD, Pellegrino CM, Levine EG, Schmotzer JA, Padula GDA, Mazurczak MA, Burdette-Radoux S, Rivkin SE, Gautam U, Hart RD, Abraham J, Kannourakis G, Underhill C, Gorddard N, Beith J, Beale P, Livshin E, White M, Hawson G, Hill J, Gill PG, Baron-Hay S, Vasey P, Lynch J, Kiberu A, Tsoi D, Epstein R, Wilson S, Gardner K, Campbell I, Villanova Biazús J, Corvalan A, Muller B, Torres R, Torres S, Letzkus J, Barajas O, Rojas H, Bravo ME, Cardemil B, Baeza R, Clerico M, Mattioli R, Visini M, Loden B, Bergh J, Malmström P, Nissborg A, Rageth C, Schoenenberger A, Popescu R, Caspar C, Senn HJ, Muñoz M, González Martín A, Catalán JG, Aramendia JM, Rifà J, López R, Llombart A, Virizuela JA, Lluch A, Martinez Jañez N, Melé M, de la Haba JR, Bohn U, Pérez Segura C, Jassem J, Neskovic-Konstantinovic Z, Dif N, Bogaerts J, Vandebroek A, Berliere M, Mitine C, Vuylsteke P, Dirix L, Moldovan C, de Lafontan B, Jouannaud C, Bachelot T, Desmoulins I, Brain E, Pierga JY, Kerbrat P, Tubiana-Mathieu N, Delecroix V, Fignon A, Saghatchian M, Fried G, Sonke S, Leeksma O, Kroep J, Moreira A, Dane F, Kleine-Tebbe A, Tessen HW, Thomssen C, Beckmann MW, Bauerfeind I, Schnappauf B, Stauder H, Grogan L, McCaffrey J, Keane M, O’Reilly S, Walshe J, Mazdai G, Makris A, Cole D, Churn M, Ines H, Todd R, Smith IE, Joji J, Perren T, Chittalia A, Ramachanara P, McCarthy JS, Kennecke H, Robidoux A, Kumar V, Dent SF, Vergidis D, Lopez PG, Grenier D, Ellard S, Pansegrau GK, Anderson JE, Diasio R, Ganz PA, Russel CA, Kroener JF, Ganey JT, Fehrenbacher L, Irwin DH, Javeed M, Anderson IC, Wapnir IL, Polikoff JA, Al-Jazayrly G, Pajon ER, Medgyesy D, Drucker BJ, Frank RC, Tepler I, Jagathambal K, Brandt DS, Isaacs C, Aggarwal A, Barr F, Biggs DD, Schwartz MA, Lilenbaum RC, Seay TE, Lebos HC, Keaton MR, Taylor MA, Bate WW, Holm C, Albain KS, Cobleigh MA, Nora RE, Wade JL, Kozloff MF, Rowland KM, Walling R, Miller KD, Dakhil SR, Mills GM, Wolff AC, Watkins SP, Hwang LC, Segal HM, Inhorn RC, Schott AF, Morris RT, Hurtubise MR, Dalton RJ, Goodwin JW, Lyss AP, Shea TC, Hopkins JO, Wall JG, Hertzel DJ, Dentchev T, Weckstein D, Kaufman PA, Catcher C, Michaelson RA, Toppmeyer DL, Klein P, Hudis CA, Leonard J, Odaimi M, Budman DR, Kalavar MR, Bloomfield CD, Budd GT, Silverman P, Gross HM, Schaefer PL, Tirumali NR, Brufsky AM, Gottlieb RJ, Domchek SM, Goldstein LJ, Luginbuhl WE, Reilly RE, Andrews WG, Hyzinski M, Sikov WM, Dizon DS, Schlabach LL, Mullins BA, Strauss JF, Green MC, Elledge RM, Unzeitig GW, Lanier KS, Stewart JA, Saphner TJ, Nambudiri GS, Tria Tirona MRB.

Author information

1
From the Peter MacCallum Cancer Centre, St. Vincent's Hospital, University of Melbourne, Melbourne, VIC, and Breast Cancer Trials Australia and New Zealand, University of Newcastle, Newcastle, NSW (P.A.F.), and the University of Sydney, Sydney (A.S.C.) - all in Australia; the Institute of Oncology of Southern Switzerland, Ospedale San Giovanni, Bellinzona (O.P.), Breast Cancer St. Gallen, St. Gallen (T.R.), and the International Breast Cancer Study Group Coordinating Center (R.M., M.R.-P., B.R., A.S.C.), University Hospital Inselspital (M.R.-P.), Bern - all in Switzerland; the University of Chicago Medical Center, Chicago (G.F.F.); the University of Calgary, Calgary, AB, Canada (B.A.W.); the Division of Medical Senology, European Institute of Oncology (M.C.), and the European Institute of Oncology and International Breast Cancer Study Group (A.G.), Milan, Ospedale Papa Giovanni XXIII, Bergamo (C.T.), Azienda Socio Sanitaria Territoriale Sette Laghi-Ospedale di Circolo and Fondazione Macchi, Varese (G.P.), Medical Oncology and Cancer Prevention, IRCCS, National Cancer Institute, Aviano (F.P., S.S.), the Department of Medicine, School of Medical Oncology, University of Udine, Udine (F.P.), Salvatore Maugeri Foundation, Pavia (L.P.), and the Hospital of Prato-Azienda Unità Sanitaria Locale Toscana Centro, Prato (A.D.L.) - all in Italy; the National Institute of Oncology, Budapest, Hungary (I.L.); Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru (H.L.G.); University Hospital 12 de Octubre, Madrid (E.C.), Vall d'Hebron Institute of Oncology and Vall d'Hebron University Hospital, Barcelona (M.B.), and Instituto Valenciano de Oncologia, Valencia (M.A.C.) - all in Spain; the Susan F. Smith Center for Women's Cancers (H.J.B., E.P.W.) and the International Breast Cancer Study Group Statistical Center, Department of Biostatistics and Computational Biology (R.D.G., M.M.R.), Dana-Farber Cancer Institute, Harvard Medical School, the Harvard T.H. Chan School of Public Health, and Frontier Science and Technology Research Foundation (R.D.G.) - all in Boston; Institut Bergonié Comprehensive Cancer Center, Université de Bordeaux, Bordeaux, France (H.R.B., M.D.); the Angeles Clinic and Research Institute, Santa Monica, CA (S.M.); Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond (C.E.G.); Mayo Clinic, Rochester, MN (M.P.G., J.N.I.); Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore (V.S.); Fred Hutchinson Cancer Research Center, University of Washington, Seattle (N.E.D.); Weston Park Hospital, Sheffield, United Kingdom (R.C.); and the Department of Obstetrics and Gynecology, University Medical Center, Regensburg, Germany (S.B.).

Abstract

BACKGROUND:

In the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT), the 5-year rates of recurrence of breast cancer were significantly lower among premenopausal women who received the aromatase inhibitor exemestane plus ovarian suppression than among those who received tamoxifen plus ovarian suppression. The addition of ovarian suppression to tamoxifen did not result in significantly lower recurrence rates than those with tamoxifen alone. Here, we report the updated results from the two trials.

METHODS:

Premenopausal women were randomly assigned to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression in SOFT and to receive tamoxifen plus ovarian suppression or exemestane plus ovarian suppression in TEXT. Randomization was stratified according to the receipt of chemotherapy.

RESULTS:

In SOFT, the 8-year disease-free survival rate was 78.9% with tamoxifen alone, 83.2% with tamoxifen plus ovarian suppression, and 85.9% with exemestane plus ovarian suppression (P=0.009 for tamoxifen alone vs. tamoxifen plus ovarian suppression). The 8-year rate of overall survival was 91.5% with tamoxifen alone, 93.3% with tamoxifen plus ovarian suppression, and 92.1% with exemestane plus ovarian suppression (P=0.01 for tamoxifen alone vs. tamoxifen plus ovarian suppression); among the women who remained premenopausal after chemotherapy, the rates were 85.1%, 89.4%, and 87.2%, respectively. Among the women with cancers that were negative for HER2 who received chemotherapy, the 8-year rate of distant recurrence with exemestane plus ovarian suppression was lower than the rate with tamoxifen plus ovarian suppression (by 7.0 percentage points in SOFT and by 5.0 percentage points in TEXT). Grade 3 or higher adverse events were reported in 24.6% of the tamoxifen-alone group, 31.0% of the tamoxifen-ovarian suppression group, and 32.3% of the exemestane-ovarian suppression group.

CONCLUSIONS:

Among premenopausal women with breast cancer, the addition of ovarian suppression to tamoxifen resulted in significantly higher 8-year rates of both disease-free and overall survival than tamoxifen alone. The use of exemestane plus ovarian suppression resulted in even higher rates of freedom from recurrence. The frequency of adverse events was higher in the two groups that received ovarian suppression than in the tamoxifen-alone group. (Funded by Pfizer and others; SOFT and TEXT ClinicalTrials.gov numbers, NCT00066690 and NCT00066703 , respectively.).

PMID:
29863451
PMCID:
PMC6193457
DOI:
10.1056/NEJMoa1803164
[Indexed for MEDLINE]
Free PMC Article

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