Adjuvant exemestane with ovarian suppression in premenopausal breast cancer

Olivia Pagani, Meredith M. Regan, Barbara A. Walley, Gini F. Fleming, Marco Colleoni, István Láng, Henry L. Gomez, Carlo Tondini, Harold J. Burstein, Edith A. Perez, Eva Ciruelos, Vered Stearns, Hervé R. Bonnefoi, Silvana Martino, Charles E. Geyer, Graziella Pinotti, Fabio Puglisi, Diana Crivellari, Thomas Ruhstaller, Eric P. Winer & 13 others Manuela Rabaglio-Poretti, Rudolf Maibach, Barbara Ruepp, Anita Giobbie-Hurder, Karen N. Price, Jürg Bernhard, Weixiu Luo, Karin Ribi, Giuseppe Viale, Alan S. Coates, Richard D. Gelber, Aron Goldhirsch, Prudence A. Francis

Research output: Contribution to journalArticle

282 Citations (Scopus)

Abstract

BACKGROUND: Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor- positive breast cancer. METHODS: In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials. RESULTS: After a median follow-up of 68 months, disease-free survival at 5 years was 91.1% in the exemestane-ovarian suppression group and 87.3% in the tamoxifen-ovarian suppression group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.72; 95% confidence interval [CI], 0.60 to 0.85; P<0.001). The rate of freedom from breast cancer at 5 years was 92.8% in the exemestane-ovarian suppression group, as compared with 88.8% in the tamoxifen-ovarian suppression group (hazard ratio for recurrence, 0.66; 95% CI, 0.55 to 0.80; P<0.001). With 194 deaths (4.1% of the patients), overall survival did not differ significantly between the two groups (hazard ratio for death in the exemestane-ovarian suppression group, 1.14; 95% CI, 0.86 to 1.51; P=0.37). Selected adverse events of grade 3 or 4 were reported for 30.6% of the patients in the exemestane-ovarian suppression group and 29.4% of those in the tamoxifen-ovarian suppression group, with profiles similar to those for postmenopausal women. CONCLUSIONS: In premenopausal women with hormone-receptor-positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence.

Original languageEnglish (US)
Pages (from-to)107-118
Number of pages12
JournalNew England Journal of Medicine
Volume371
Issue number2
DOIs
StatePublished - 2014

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exemestane
Tamoxifen
Breast Neoplasms
Aromatase Inhibitors
Hormones
Confidence Intervals
Recurrence
Triptorelin Pamoate
Second Primary Neoplasms
Ovariectomy
Gonadotropin-Releasing Hormone
Disease-Free Survival
Estrogens

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Pagani, O., Regan, M. M., Walley, B. A., Fleming, G. F., Colleoni, M., Láng, I., ... Francis, P. A. (2014). Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. New England Journal of Medicine, 371(2), 107-118. https://doi.org/10.1056/NEJMoa1404037

Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. / Pagani, Olivia; Regan, Meredith M.; Walley, Barbara A.; Fleming, Gini F.; Colleoni, Marco; Láng, István; Gomez, Henry L.; Tondini, Carlo; Burstein, Harold J.; Perez, Edith A.; Ciruelos, Eva; Stearns, Vered; Bonnefoi, Hervé R.; Martino, Silvana; Geyer, Charles E.; Pinotti, Graziella; Puglisi, Fabio; Crivellari, Diana; Ruhstaller, Thomas; Winer, Eric P.; Rabaglio-Poretti, Manuela; Maibach, Rudolf; Ruepp, Barbara; Giobbie-Hurder, Anita; Price, Karen N.; Bernhard, Jürg; Luo, Weixiu; Ribi, Karin; Viale, Giuseppe; Coates, Alan S.; Gelber, Richard D.; Goldhirsch, Aron; Francis, Prudence A.

In: New England Journal of Medicine, Vol. 371, No. 2, 2014, p. 107-118.

Research output: Contribution to journalArticle

Pagani, O, Regan, MM, Walley, BA, Fleming, GF, Colleoni, M, Láng, I, Gomez, HL, Tondini, C, Burstein, HJ, Perez, EA, Ciruelos, E, Stearns, V, Bonnefoi, HR, Martino, S, Geyer, CE, Pinotti, G, Puglisi, F, Crivellari, D, Ruhstaller, T, Winer, EP, Rabaglio-Poretti, M, Maibach, R, Ruepp, B, Giobbie-Hurder, A, Price, KN, Bernhard, J, Luo, W, Ribi, K, Viale, G, Coates, AS, Gelber, RD, Goldhirsch, A & Francis, PA 2014, 'Adjuvant exemestane with ovarian suppression in premenopausal breast cancer', New England Journal of Medicine, vol. 371, no. 2, pp. 107-118. https://doi.org/10.1056/NEJMoa1404037
Pagani, Olivia ; Regan, Meredith M. ; Walley, Barbara A. ; Fleming, Gini F. ; Colleoni, Marco ; Láng, István ; Gomez, Henry L. ; Tondini, Carlo ; Burstein, Harold J. ; Perez, Edith A. ; Ciruelos, Eva ; Stearns, Vered ; Bonnefoi, Hervé R. ; Martino, Silvana ; Geyer, Charles E. ; Pinotti, Graziella ; Puglisi, Fabio ; Crivellari, Diana ; Ruhstaller, Thomas ; Winer, Eric P. ; Rabaglio-Poretti, Manuela ; Maibach, Rudolf ; Ruepp, Barbara ; Giobbie-Hurder, Anita ; Price, Karen N. ; Bernhard, Jürg ; Luo, Weixiu ; Ribi, Karin ; Viale, Giuseppe ; Coates, Alan S. ; Gelber, Richard D. ; Goldhirsch, Aron ; Francis, Prudence A. / Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. In: New England Journal of Medicine. 2014 ; Vol. 371, No. 2. pp. 107-118.
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abstract = "BACKGROUND: Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor- positive breast cancer. METHODS: In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials. RESULTS: After a median follow-up of 68 months, disease-free survival at 5 years was 91.1{\%} in the exemestane-ovarian suppression group and 87.3{\%} in the tamoxifen-ovarian suppression group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.72; 95{\%} confidence interval [CI], 0.60 to 0.85; P<0.001). The rate of freedom from breast cancer at 5 years was 92.8{\%} in the exemestane-ovarian suppression group, as compared with 88.8{\%} in the tamoxifen-ovarian suppression group (hazard ratio for recurrence, 0.66; 95{\%} CI, 0.55 to 0.80; P<0.001). With 194 deaths (4.1{\%} of the patients), overall survival did not differ significantly between the two groups (hazard ratio for death in the exemestane-ovarian suppression group, 1.14; 95{\%} CI, 0.86 to 1.51; P=0.37). Selected adverse events of grade 3 or 4 were reported for 30.6{\%} of the patients in the exemestane-ovarian suppression group and 29.4{\%} of those in the tamoxifen-ovarian suppression group, with profiles similar to those for postmenopausal women. CONCLUSIONS: In premenopausal women with hormone-receptor-positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence.",
author = "Olivia Pagani and Regan, {Meredith M.} and Walley, {Barbara A.} and Fleming, {Gini F.} and Marco Colleoni and Istv{\'a}n L{\'a}ng and Gomez, {Henry L.} and Carlo Tondini and Burstein, {Harold J.} and Perez, {Edith A.} and Eva Ciruelos and Vered Stearns and Bonnefoi, {Herv{\'e} R.} and Silvana Martino and Geyer, {Charles E.} and Graziella Pinotti and Fabio Puglisi and Diana Crivellari and Thomas Ruhstaller and Winer, {Eric P.} and Manuela Rabaglio-Poretti and Rudolf Maibach and Barbara Ruepp and Anita Giobbie-Hurder and Price, {Karen N.} and J{\"u}rg Bernhard and Weixiu Luo and Karin Ribi and Giuseppe Viale and Coates, {Alan S.} and Gelber, {Richard D.} and Aron Goldhirsch and Francis, {Prudence A.}",
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T1 - Adjuvant exemestane with ovarian suppression in premenopausal breast cancer

AU - Pagani, Olivia

AU - Regan, Meredith M.

AU - Walley, Barbara A.

AU - Fleming, Gini F.

AU - Colleoni, Marco

AU - Láng, István

AU - Gomez, Henry L.

AU - Tondini, Carlo

AU - Burstein, Harold J.

AU - Perez, Edith A.

AU - Ciruelos, Eva

AU - Stearns, Vered

AU - Bonnefoi, Hervé R.

AU - Martino, Silvana

AU - Geyer, Charles E.

AU - Pinotti, Graziella

AU - Puglisi, Fabio

AU - Crivellari, Diana

AU - Ruhstaller, Thomas

AU - Winer, Eric P.

AU - Rabaglio-Poretti, Manuela

AU - Maibach, Rudolf

AU - Ruepp, Barbara

AU - Giobbie-Hurder, Anita

AU - Price, Karen N.

AU - Bernhard, Jürg

AU - Luo, Weixiu

AU - Ribi, Karin

AU - Viale, Giuseppe

AU - Coates, Alan S.

AU - Gelber, Richard D.

AU - Goldhirsch, Aron

AU - Francis, Prudence A.

PY - 2014

Y1 - 2014

N2 - BACKGROUND: Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor- positive breast cancer. METHODS: In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials. RESULTS: After a median follow-up of 68 months, disease-free survival at 5 years was 91.1% in the exemestane-ovarian suppression group and 87.3% in the tamoxifen-ovarian suppression group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.72; 95% confidence interval [CI], 0.60 to 0.85; P<0.001). The rate of freedom from breast cancer at 5 years was 92.8% in the exemestane-ovarian suppression group, as compared with 88.8% in the tamoxifen-ovarian suppression group (hazard ratio for recurrence, 0.66; 95% CI, 0.55 to 0.80; P<0.001). With 194 deaths (4.1% of the patients), overall survival did not differ significantly between the two groups (hazard ratio for death in the exemestane-ovarian suppression group, 1.14; 95% CI, 0.86 to 1.51; P=0.37). Selected adverse events of grade 3 or 4 were reported for 30.6% of the patients in the exemestane-ovarian suppression group and 29.4% of those in the tamoxifen-ovarian suppression group, with profiles similar to those for postmenopausal women. CONCLUSIONS: In premenopausal women with hormone-receptor-positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence.

AB - BACKGROUND: Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor- positive breast cancer. METHODS: In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials. RESULTS: After a median follow-up of 68 months, disease-free survival at 5 years was 91.1% in the exemestane-ovarian suppression group and 87.3% in the tamoxifen-ovarian suppression group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.72; 95% confidence interval [CI], 0.60 to 0.85; P<0.001). The rate of freedom from breast cancer at 5 years was 92.8% in the exemestane-ovarian suppression group, as compared with 88.8% in the tamoxifen-ovarian suppression group (hazard ratio for recurrence, 0.66; 95% CI, 0.55 to 0.80; P<0.001). With 194 deaths (4.1% of the patients), overall survival did not differ significantly between the two groups (hazard ratio for death in the exemestane-ovarian suppression group, 1.14; 95% CI, 0.86 to 1.51; P=0.37). Selected adverse events of grade 3 or 4 were reported for 30.6% of the patients in the exemestane-ovarian suppression group and 29.4% of those in the tamoxifen-ovarian suppression group, with profiles similar to those for postmenopausal women. CONCLUSIONS: In premenopausal women with hormone-receptor-positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence.

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