title: Absolute Benefit of Adjuvant Endocrine Therapies for Premenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer: TEXT and SOFT Trials.
abstract: Risk of recurrence is the primary consideration in breast cancer adjuvant therapy recommendations. The TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) trials investigated adjuvant endocrine therapies for premenopausal women with hormone receptor-positive breast cancer, testing exemestane plus ovarian function suppression (OFS), tamoxifen plus OFS, and tamoxifen alone. We examined absolute treatment effect across a continuum of recurrence risk to individualize endocrine therapy decision making for premenopausal women with human epidermal growth factor receptor 2 (HER2) -negative disease.
  
  
  
  The TEXT and SOFT hormone receptor-positive, HER2-negative analysis population included 4,891 women. The end point was breast cancer-free interval (BCFI), defined as time from random assignment to first occurrence of invasive locoregional, distant, or contralateral breast cancer. A continuous, composite measure of recurrence risk for each patient was determined from a Cox model incorporating age, nodal status, tumor size and grade, and estrogen receptor, progesterone receptor, and Ki-67 expression levels. Subpopulation treatment effect pattern plot methodology revealed differential treatment effects on 5-year BCFI according to composite risk.
  
  
  
  SOFT patients who remained premenopausal after chemotherapy experienced absolute improvement of 5% or more in 5-year BCFI with exemestane plus OFS versus tamoxifen plus OFS or tamoxifen alone, reaching 10% to 15% at intermediate to high composite risk; the benefit of tamoxifen plus OFS versus tamoxifen alone was apparent at the highest composite risk. The SOFT no-chemotherapy cohort-for whom composite risk was lowest on average-did well with all endocrine therapies. For TEXT patients, the benefit of exemestane plus OFS versus tamoxifen plus OFS in 5-year BCFI ranged from 5% to 15%; patients not receiving chemotherapy and with lowest composite risk did well with both treatments.
  
  
  
  Premenopausal women with hormone receptor-positive, HER2-negative disease and high recurrence risk, as defined by clinicopathologic characteristics, may experience improvement of 10% to 15% in 5-year BCFI with exemestane plus OFS versus tamoxifen alone. An improvement of at least 5% may be achieved for women at intermediate risk, and improvement is minimal for those at lowest risk.
authors.affiliation: Meredith M. Regan and Richard D. Gelber, Dana-Farber Cancer Institute, Harvard Medical School; Karen N. Price and Richard D. Gelber, Frontier Science and Technology Research Foundation; Richard D. Gelber, Harvard T.H. Chan School of Public Health, Boston, MA; Prudence A. Francis, MacCallum Cancer Center, St Vincent's Hospital, University of Melbourne, Melbourne; University of Newcastle, Newcastle; Alan S. Coates, University of Sydney, Sydney, Australia; Olivia Pagani, Institute of Oncology of Southern Switzerland, Lugano Viganello, Switzerland; Gini F. Fleming, University of Chicago Medical Center, Chicago, IL; Barbara A. Walley, National Cancer Institute of Canada Clinical Trials Group, Calgary, Alberta, Canada; Giuseppe Viale, University of Milan; Giuseppe Viale, Marco Colleoni, and Aron Goldhirsch, European Institute of Oncology, Milan; Carlo Tondini, Ospedale Papa Giovanni XXIII, Bergamo; Graziella Pinotti, Ospedale di Circolo and Fondazione Macchi, Varese, Italy; István Láng, National Institute of Oncology, Budapest, Hungary; Henry L. Gómez, Instituto Nacional de Enfermedades Neoplásticas, Lima, Peru. mregan@jimmy.harvard.edu.
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Regan
authors.affiliation: Meredith M. Regan and Richard D. Gelber, Dana-Farber Cancer Institute, Harvard Medical School; Karen N. Price and Richard D. Gelber, Frontier Science and Technology Research Foundation; Richard D. Gelber, Harvard T.H. Chan School of Public Health, Boston, MA; Prudence A. Francis, MacCallum Cancer Center, St Vincent's Hospital, University of Melbourne, Melbourne; University of Newcastle, Newcastle; Alan S. Coates, University of Sydney, Sydney, Australia; Olivia Pagani, Institute of Oncology of Southern Switzerland, Lugano Viganello, Switzerland; Gini F. Fleming, University of Chicago Medical Center, Chicago, IL; Barbara A. Walley, National Cancer Institute of Canada Clinical Trials Group, Calgary, Alberta, Canada; Giuseppe Viale, University of Milan; Giuseppe Viale, Marco Colleoni, and Aron Goldhirsch, European Institute of Oncology, Milan; Carlo Tondini, Ospedale Papa Giovanni XXIII, Bergamo; Graziella Pinotti, Ospedale di Circolo and Fondazione Macchi, Varese, Italy; István Láng, National Institute of Oncology, Budapest, Hungary; Henry L. Gómez, Instituto Nacional de Enfermedades Neoplásticas, Lima, Peru.
authors.forename: Prudence A
authors.initials: PA
authors.lastname: Francis
authors.affiliation: Meredith M. Regan and Richard D. Gelber, Dana-Farber Cancer Institute, Harvard Medical School; Karen N. Price and Richard D. Gelber, Frontier Science and Technology Research Foundation; Richard D. Gelber, Harvard T.H. Chan School of Public Health, Boston, MA; Prudence A. Francis, MacCallum Cancer Center, St Vincent's Hospital, University of Melbourne, Melbourne; University of Newcastle, Newcastle; Alan S. Coates, University of Sydney, Sydney, Australia; Olivia Pagani, Institute of Oncology of Southern Switzerland, Lugano Viganello, Switzerland; Gini F. Fleming, University of Chicago Medical Center, Chicago, IL; Barbara A. Walley, National Cancer Institute of Canada Clinical Trials Group, Calgary, Alberta, Canada; Giuseppe Viale, University of Milan; Giuseppe Viale, Marco Colleoni, and Aron Goldhirsch, European Institute of Oncology, Milan; Carlo Tondini, Ospedale Papa Giovanni XXIII, Bergamo; Graziella Pinotti, Ospedale di Circolo and Fondazione Macchi, Varese, Italy; István Láng, National Institute of Oncology, Budapest, Hungary; Henry L. Gómez, Instituto Nacional de Enfermedades Neoplásticas, Lima, Peru.
authors.forename: Olivia
authors.initials: O
authors.lastname: Pagani
authors.affiliation: Meredith M. Regan and Richard D. Gelber, Dana-Farber Cancer Institute, Harvard Medical School; Karen N. Price and Richard D. Gelber, Frontier Science and Technology Research Foundation; Richard D. Gelber, Harvard T.H. Chan School of Public Health, Boston, MA; Prudence A. Francis, MacCallum Cancer Center, St Vincent's Hospital, University of Melbourne, Melbourne; University of Newcastle, Newcastle; Alan S. Coates, University of Sydney, Sydney, Australia; Olivia Pagani, Institute of Oncology of Southern Switzerland, Lugano Viganello, Switzerland; Gini F. Fleming, University of Chicago Medical Center, Chicago, IL; Barbara A. Walley, National Cancer Institute of Canada Clinical Trials Group, Calgary, Alberta, Canada; Giuseppe Viale, University of Milan; Giuseppe Viale, Marco Colleoni, and Aron Goldhirsch, European Institute of Oncology, Milan; Carlo Tondini, Ospedale Papa Giovanni XXIII, Bergamo; Graziella Pinotti, Ospedale di Circolo and Fondazione Macchi, Varese, Italy; István Láng, National Institute of Oncology, Budapest, Hungary; Henry L. Gómez, Instituto Nacional de Enfermedades Neoplásticas, Lima, Peru.
authors.forename: Gini F
authors.initials: GF
authors.lastname: Fleming
authors.affiliation: Meredith M. Regan and Richard D. Gelber, Dana-Farber Cancer Institute, Harvard Medical School; Karen N. Price and Richard D. Gelber, Frontier Science and Technology Research Foundation; Richard D. Gelber, Harvard T.H. Chan School of Public Health, Boston, MA; Prudence A. Francis, MacCallum Cancer Center, St Vincent's Hospital, University of Melbourne, Melbourne; University of Newcastle, Newcastle; Alan S. Coates, University of Sydney, Sydney, Australia; Olivia Pagani, Institute of Oncology of Southern Switzerland, Lugano Viganello, Switzerland; Gini F. Fleming, University of Chicago Medical Center, Chicago, IL; Barbara A. Walley, National Cancer Institute of Canada Clinical Trials Group, Calgary, Alberta, Canada; Giuseppe Viale, University of Milan; Giuseppe Viale, Marco Colleoni, and Aron Goldhirsch, European Institute of Oncology, Milan; Carlo Tondini, Ospedale Papa Giovanni XXIII, Bergamo; Graziella Pinotti, Ospedale di Circolo and Fondazione Macchi, Varese, Italy; István Láng, National Institute of Oncology, Budapest, Hungary; Henry L. Gómez, Instituto Nacional de Enfermedades Neoplásticas, Lima, Peru.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Walley
authors.affiliation: Meredith M. Regan and Richard D. Gelber, Dana-Farber Cancer Institute, Harvard Medical School; Karen N. Price and Richard D. Gelber, Frontier Science and Technology Research Foundation; Richard D. Gelber, Harvard T.H. Chan School of Public Health, Boston, MA; Prudence A. Francis, MacCallum Cancer Center, St Vincent's Hospital, University of Melbourne, Melbourne; University of Newcastle, Newcastle; Alan S. Coates, University of Sydney, Sydney, Australia; Olivia Pagani, Institute of Oncology of Southern Switzerland, Lugano Viganello, Switzerland; Gini F. Fleming, University of Chicago Medical Center, Chicago, IL; Barbara A. Walley, National Cancer Institute of Canada Clinical Trials Group, Calgary, Alberta, Canada; Giuseppe Viale, University of Milan; Giuseppe Viale, Marco Colleoni, and Aron Goldhirsch, European Institute of Oncology, Milan; Carlo Tondini, Ospedale Papa Giovanni XXIII, Bergamo; Graziella Pinotti, Ospedale di Circolo and Fondazione Macchi, Varese, Italy; István Láng, National Institute of Oncology, Budapest, Hungary; Henry L. Gómez, Instituto Nacional de Enfermedades Neoplásticas, Lima, Peru.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.affiliation: Meredith M. Regan and Richard D. Gelber, Dana-Farber Cancer Institute, Harvard Medical School; Karen N. Price and Richard D. Gelber, Frontier Science and Technology Research Foundation; Richard D. Gelber, Harvard T.H. Chan School of Public Health, Boston, MA; Prudence A. Francis, MacCallum Cancer Center, St Vincent's Hospital, University of Melbourne, Melbourne; University of Newcastle, Newcastle; Alan S. Coates, University of Sydney, Sydney, Australia; Olivia Pagani, Institute of Oncology of Southern Switzerland, Lugano Viganello, Switzerland; Gini F. Fleming, University of Chicago Medical Center, Chicago, IL; Barbara A. Walley, National Cancer Institute of Canada Clinical Trials Group, Calgary, Alberta, Canada; Giuseppe Viale, University of Milan; Giuseppe Viale, Marco Colleoni, and Aron Goldhirsch, European Institute of Oncology, Milan; Carlo Tondini, Ospedale Papa Giovanni XXIII, Bergamo; Graziella Pinotti, Ospedale di Circolo and Fondazione Macchi, Varese, Italy; István Láng, National Institute of Oncology, Budapest, Hungary; Henry L. Gómez, Instituto Nacional de Enfermedades Neoplásticas, Lima, Peru.
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
authors.affiliation: Meredith M. Regan and Richard D. Gelber, Dana-Farber Cancer Institute, Harvard Medical School; Karen N. Price and Richard D. Gelber, Frontier Science and Technology Research Foundation; Richard D. Gelber, Harvard T.H. Chan School of Public Health, Boston, MA; Prudence A. Francis, MacCallum Cancer Center, St Vincent's Hospital, University of Melbourne, Melbourne; University of Newcastle, Newcastle; Alan S. Coates, University of Sydney, Sydney, Australia; Olivia Pagani, Institute of Oncology of Southern Switzerland, Lugano Viganello, Switzerland; Gini F. Fleming, University of Chicago Medical Center, Chicago, IL; Barbara A. Walley, National Cancer Institute of Canada Clinical Trials Group, Calgary, Alberta, Canada; Giuseppe Viale, University of Milan; Giuseppe Viale, Marco Colleoni, and Aron Goldhirsch, European Institute of Oncology, Milan; Carlo Tondini, Ospedale Papa Giovanni XXIII, Bergamo; Graziella Pinotti, Ospedale di Circolo and Fondazione Macchi, Varese, Italy; István Láng, National Institute of Oncology, Budapest, Hungary; Henry L. Gómez, Instituto Nacional de Enfermedades Neoplásticas, Lima, Peru.
authors.forename: István
authors.initials: I
authors.lastname: Láng
authors.affiliation: Meredith M. Regan and Richard D. Gelber, Dana-Farber Cancer Institute, Harvard Medical School; Karen N. Price and Richard D. Gelber, Frontier Science and Technology Research Foundation; Richard D. Gelber, Harvard T.H. Chan School of Public Health, Boston, MA; Prudence A. Francis, MacCallum Cancer Center, St Vincent's Hospital, University of Melbourne, Melbourne; University of Newcastle, Newcastle; Alan S. Coates, University of Sydney, Sydney, Australia; Olivia Pagani, Institute of Oncology of Southern Switzerland, Lugano Viganello, Switzerland; Gini F. Fleming, University of Chicago Medical Center, Chicago, IL; Barbara A. Walley, National Cancer Institute of Canada Clinical Trials Group, Calgary, Alberta, Canada; Giuseppe Viale, University of Milan; Giuseppe Viale, Marco Colleoni, and Aron Goldhirsch, European Institute of Oncology, Milan; Carlo Tondini, Ospedale Papa Giovanni XXIII, Bergamo; Graziella Pinotti, Ospedale di Circolo and Fondazione Macchi, Varese, Italy; István Láng, National Institute of Oncology, Budapest, Hungary; Henry L. Gómez, Instituto Nacional de Enfermedades Neoplásticas, Lima, Peru.
authors.forename: Henry L
authors.initials: HL
authors.lastname: Gómez
authors.affiliation: Meredith M. Regan and Richard D. Gelber, Dana-Farber Cancer Institute, Harvard Medical School; Karen N. Price and Richard D. Gelber, Frontier Science and Technology Research Foundation; Richard D. Gelber, Harvard T.H. Chan School of Public Health, Boston, MA; Prudence A. Francis, MacCallum Cancer Center, St Vincent's Hospital, University of Melbourne, Melbourne; University of Newcastle, Newcastle; Alan S. Coates, University of Sydney, Sydney, Australia; Olivia Pagani, Institute of Oncology of Southern Switzerland, Lugano Viganello, Switzerland; Gini F. Fleming, University of Chicago Medical Center, Chicago, IL; Barbara A. Walley, National Cancer Institute of Canada Clinical Trials Group, Calgary, Alberta, Canada; Giuseppe Viale, University of Milan; Giuseppe Viale, Marco Colleoni, and Aron Goldhirsch, European Institute of Oncology, Milan; Carlo Tondini, Ospedale Papa Giovanni XXIII, Bergamo; Graziella Pinotti, Ospedale di Circolo and Fondazione Macchi, Varese, Italy; István Láng, National Institute of Oncology, Budapest, Hungary; Henry L. Gómez, Instituto Nacional de Enfermedades Neoplásticas, Lima, Peru.
authors.forename: Carlo
authors.initials: C
authors.lastname: Tondini
authors.affiliation: Meredith M. Regan and Richard D. Gelber, Dana-Farber Cancer Institute, Harvard Medical School; Karen N. Price and Richard D. Gelber, Frontier Science and Technology Research Foundation; Richard D. Gelber, Harvard T.H. Chan School of Public Health, Boston, MA; Prudence A. Francis, MacCallum Cancer Center, St Vincent's Hospital, University of Melbourne, Melbourne; University of Newcastle, Newcastle; Alan S. Coates, University of Sydney, Sydney, Australia; Olivia Pagani, Institute of Oncology of Southern Switzerland, Lugano Viganello, Switzerland; Gini F. Fleming, University of Chicago Medical Center, Chicago, IL; Barbara A. Walley, National Cancer Institute of Canada Clinical Trials Group, Calgary, Alberta, Canada; Giuseppe Viale, University of Milan; Giuseppe Viale, Marco Colleoni, and Aron Goldhirsch, European Institute of Oncology, Milan; Carlo Tondini, Ospedale Papa Giovanni XXIII, Bergamo; Graziella Pinotti, Ospedale di Circolo and Fondazione Macchi, Varese, Italy; István Láng, National Institute of Oncology, Budapest, Hungary; Henry L. Gómez, Instituto Nacional de Enfermedades Neoplásticas, Lima, Peru.
authors.forename: Graziella
authors.initials: G
authors.lastname: Pinotti
authors.affiliation: Meredith M. Regan and Richard D. Gelber, Dana-Farber Cancer Institute, Harvard Medical School; Karen N. Price and Richard D. Gelber, Frontier Science and Technology Research Foundation; Richard D. Gelber, Harvard T.H. Chan School of Public Health, Boston, MA; Prudence A. Francis, MacCallum Cancer Center, St Vincent's Hospital, University of Melbourne, Melbourne; University of Newcastle, Newcastle; Alan S. Coates, University of Sydney, Sydney, Australia; Olivia Pagani, Institute of Oncology of Southern Switzerland, Lugano Viganello, Switzerland; Gini F. Fleming, University of Chicago Medical Center, Chicago, IL; Barbara A. Walley, National Cancer Institute of Canada Clinical Trials Group, Calgary, Alberta, Canada; Giuseppe Viale, University of Milan; Giuseppe Viale, Marco Colleoni, and Aron Goldhirsch, European Institute of Oncology, Milan; Carlo Tondini, Ospedale Papa Giovanni XXIII, Bergamo; Graziella Pinotti, Ospedale di Circolo and Fondazione Macchi, Varese, Italy; István Láng, National Institute of Oncology, Budapest, Hungary; Henry L. Gómez, Instituto Nacional de Enfermedades Neoplásticas, Lima, Peru.
authors.forename: Karen N
authors.initials: KN
authors.lastname: Price
authors.affiliation: Meredith M. Regan and Richard D. Gelber, Dana-Farber Cancer Institute, Harvard Medical School; Karen N. Price and Richard D. Gelber, Frontier Science and Technology Research Foundation; Richard D. Gelber, Harvard T.H. Chan School of Public Health, Boston, MA; Prudence A. Francis, MacCallum Cancer Center, St Vincent's Hospital, University of Melbourne, Melbourne; University of Newcastle, Newcastle; Alan S. Coates, University of Sydney, Sydney, Australia; Olivia Pagani, Institute of Oncology of Southern Switzerland, Lugano Viganello, Switzerland; Gini F. Fleming, University of Chicago Medical Center, Chicago, IL; Barbara A. Walley, National Cancer Institute of Canada Clinical Trials Group, Calgary, Alberta, Canada; Giuseppe Viale, University of Milan; Giuseppe Viale, Marco Colleoni, and Aron Goldhirsch, European Institute of Oncology, Milan; Carlo Tondini, Ospedale Papa Giovanni XXIII, Bergamo; Graziella Pinotti, Ospedale di Circolo and Fondazione Macchi, Varese, Italy; István Láng, National Institute of Oncology, Budapest, Hungary; Henry L. Gómez, Instituto Nacional de Enfermedades Neoplásticas, Lima, Peru.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Coates
authors.affiliation: Meredith M. Regan and Richard D. Gelber, Dana-Farber Cancer Institute, Harvard Medical School; Karen N. Price and Richard D. Gelber, Frontier Science and Technology Research Foundation; Richard D. Gelber, Harvard T.H. Chan School of Public Health, Boston, MA; Prudence A. Francis, MacCallum Cancer Center, St Vincent's Hospital, University of Melbourne, Melbourne; University of Newcastle, Newcastle; Alan S. Coates, University of Sydney, Sydney, Australia; Olivia Pagani, Institute of Oncology of Southern Switzerland, Lugano Viganello, Switzerland; Gini F. Fleming, University of Chicago Medical Center, Chicago, IL; Barbara A. Walley, National Cancer Institute of Canada Clinical Trials Group, Calgary, Alberta, Canada; Giuseppe Viale, University of Milan; Giuseppe Viale, Marco Colleoni, and Aron Goldhirsch, European Institute of Oncology, Milan; Carlo Tondini, Ospedale Papa Giovanni XXIII, Bergamo; Graziella Pinotti, Ospedale di Circolo and Fondazione Macchi, Varese, Italy; István Láng, National Institute of Oncology, Budapest, Hungary; Henry L. Gómez, Instituto Nacional de Enfermedades Neoplásticas, Lima, Peru.
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.affiliation: Meredith M. Regan and Richard D. Gelber, Dana-Farber Cancer Institute, Harvard Medical School; Karen N. Price and Richard D. Gelber, Frontier Science and Technology Research Foundation; Richard D. Gelber, Harvard T.H. Chan School of Public Health, Boston, MA; Prudence A. Francis, MacCallum Cancer Center, St Vincent's Hospital, University of Melbourne, Melbourne; University of Newcastle, Newcastle; Alan S. Coates, University of Sydney, Sydney, Australia; Olivia Pagani, Institute of Oncology of Southern Switzerland, Lugano Viganello, Switzerland; Gini F. Fleming, University of Chicago Medical Center, Chicago, IL; Barbara A. Walley, National Cancer Institute of Canada Clinical Trials Group, Calgary, Alberta, Canada; Giuseppe Viale, University of Milan; Giuseppe Viale, Marco Colleoni, and Aron Goldhirsch, European Institute of Oncology, Milan; Carlo Tondini, Ospedale Papa Giovanni XXIII, Bergamo; Graziella Pinotti, Ospedale di Circolo and Fondazione Macchi, Varese, Italy; István Láng, National Institute of Oncology, Budapest, Hungary; Henry L. Gómez, Instituto Nacional de Enfermedades Neoplásticas, Lima, Peru.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
mesh_terms: D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010053:Ovary / Q000503:physiopathology; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis*; D013629:Tamoxifen / Q000008:administration & dosage*
chemical_list: D000730:Androstadienes; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D013629:Tamoxifen; C508053:ERBB2 protein, human; C056516:exemestane