Adjuvant ovarian suppression in premenopausal breast cancer

Prudence A. Francis, Meredith M. Regan, Gini F. Fleming, István Láng, Eva Ciruelos, Meritxell Bellet, Hervé R. Bonnefoi, Miguel A. Climent, Gian Antonio Da Prada, Harold J. Burstein, Silvana Martino, Nancy E. Davidson, Charles E. Geyer, Barbara A. Walley, Robert Coleman, Pierre Kerbrat, Stefan Buchholz, James N. Ingle, E. P Manuela Winer, Manuela Rabaglio-PorettiRudolf Maibach, Barbara Ruepp, Anita Giobbie-Hurder, Karen N. Price, Marco Colleoni, Giuseppe Viale, Alan S. Coates, Aron Goldhirsch, Richard D. Gelber

Research output: Contribution to journalArticle

299 Citations (Scopus)

Abstract

BACKGROUND Suppression of ovarian estrogen production reduces the recurrence of hormonereceptor- positive early breast cancer in premenopausal women, but its value when added to tamoxifen is uncertain.

METHODS We randomly assigned 3066 premenopausal women, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. The primary analysis tested the hypothesis that tamoxifen plus ovarian suppression would improve disease-free survival, as compared with tamoxifen alone. In the primary analysis, 46.7% of the patients had not received chemotherapy previously, and 53.3% had received chemotherapy and remained premenopausal.

RESULTS After a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen-ovarian suppression group and 84.7% in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% confidence interval [CI], 0.66 to 1.04; P = 0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone (hazard ratio, 0.78; 95% CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5% in the tamoxifen-ovarian suppression group and 78.0% in the tamoxifen group (hazard ratio for recurrence, 0.78; 95% CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7% in the exemestane-ovarian suppression group (hazard ratio for recurrence vs. tamoxifen, 0.65; 95% CI, 0.49 to 0.87).

CONCLUSIONS Adding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes. Further improvement was seen with the use of exemestane plus ovarian suppression.

Original languageEnglish (US)
Pages (from-to)436-446
Number of pages11
JournalNew England Journal of Medicine
Volume372
Issue number5
DOIs
StatePublished - Jan 1 2015

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Tamoxifen
Breast Neoplasms
exemestane
Recurrence
Confidence Intervals
Drug Therapy
Disease-Free Survival
Second Primary Neoplasms
Adjuvant Chemotherapy
Estrogens
Survival Rate

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Francis, P. A., Regan, M. M., Fleming, G. F., Láng, I., Ciruelos, E., Bellet, M., ... Gelber, R. D. (2015). Adjuvant ovarian suppression in premenopausal breast cancer. New England Journal of Medicine, 372(5), 436-446. https://doi.org/10.1056/NEJMoa1412379

Adjuvant ovarian suppression in premenopausal breast cancer. / Francis, Prudence A.; Regan, Meredith M.; Fleming, Gini F.; Láng, István; Ciruelos, Eva; Bellet, Meritxell; Bonnefoi, Hervé R.; Climent, Miguel A.; Da Prada, Gian Antonio; Burstein, Harold J.; Martino, Silvana; Davidson, Nancy E.; Geyer, Charles E.; Walley, Barbara A.; Coleman, Robert; Kerbrat, Pierre; Buchholz, Stefan; Ingle, James N.; Winer, E. P Manuela; Rabaglio-Poretti, Manuela; Maibach, Rudolf; Ruepp, Barbara; Giobbie-Hurder, Anita; Price, Karen N.; Colleoni, Marco; Viale, Giuseppe; Coates, Alan S.; Goldhirsch, Aron; Gelber, Richard D.

In: New England Journal of Medicine, Vol. 372, No. 5, 01.01.2015, p. 436-446.

Research output: Contribution to journalArticle

Francis, PA, Regan, MM, Fleming, GF, Láng, I, Ciruelos, E, Bellet, M, Bonnefoi, HR, Climent, MA, Da Prada, GA, Burstein, HJ, Martino, S, Davidson, NE, Geyer, CE, Walley, BA, Coleman, R, Kerbrat, P, Buchholz, S, Ingle, JN, Winer, EPM, Rabaglio-Poretti, M, Maibach, R, Ruepp, B, Giobbie-Hurder, A, Price, KN, Colleoni, M, Viale, G, Coates, AS, Goldhirsch, A & Gelber, RD 2015, 'Adjuvant ovarian suppression in premenopausal breast cancer', New England Journal of Medicine, vol. 372, no. 5, pp. 436-446. https://doi.org/10.1056/NEJMoa1412379
Francis PA, Regan MM, Fleming GF, Láng I, Ciruelos E, Bellet M et al. Adjuvant ovarian suppression in premenopausal breast cancer. New England Journal of Medicine. 2015 Jan 1;372(5):436-446. https://doi.org/10.1056/NEJMoa1412379
Francis, Prudence A. ; Regan, Meredith M. ; Fleming, Gini F. ; Láng, István ; Ciruelos, Eva ; Bellet, Meritxell ; Bonnefoi, Hervé R. ; Climent, Miguel A. ; Da Prada, Gian Antonio ; Burstein, Harold J. ; Martino, Silvana ; Davidson, Nancy E. ; Geyer, Charles E. ; Walley, Barbara A. ; Coleman, Robert ; Kerbrat, Pierre ; Buchholz, Stefan ; Ingle, James N. ; Winer, E. P Manuela ; Rabaglio-Poretti, Manuela ; Maibach, Rudolf ; Ruepp, Barbara ; Giobbie-Hurder, Anita ; Price, Karen N. ; Colleoni, Marco ; Viale, Giuseppe ; Coates, Alan S. ; Goldhirsch, Aron ; Gelber, Richard D. / Adjuvant ovarian suppression in premenopausal breast cancer. In: New England Journal of Medicine. 2015 ; Vol. 372, No. 5. pp. 436-446.
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abstract = "BACKGROUND Suppression of ovarian estrogen production reduces the recurrence of hormonereceptor- positive early breast cancer in premenopausal women, but its value when added to tamoxifen is uncertain.METHODS We randomly assigned 3066 premenopausal women, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. The primary analysis tested the hypothesis that tamoxifen plus ovarian suppression would improve disease-free survival, as compared with tamoxifen alone. In the primary analysis, 46.7{\%} of the patients had not received chemotherapy previously, and 53.3{\%} had received chemotherapy and remained premenopausal.RESULTS After a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6{\%} in the tamoxifen-ovarian suppression group and 84.7{\%} in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95{\%} confidence interval [CI], 0.66 to 1.04; P = 0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone (hazard ratio, 0.78; 95{\%} CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5{\%} in the tamoxifen-ovarian suppression group and 78.0{\%} in the tamoxifen group (hazard ratio for recurrence, 0.78; 95{\%} CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7{\%} in the exemestane-ovarian suppression group (hazard ratio for recurrence vs. tamoxifen, 0.65; 95{\%} CI, 0.49 to 0.87).CONCLUSIONS Adding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes. Further improvement was seen with the use of exemestane plus ovarian suppression.",
author = "Francis, {Prudence A.} and Regan, {Meredith M.} and Fleming, {Gini F.} and Istv{\'a}n L{\'a}ng and Eva Ciruelos and Meritxell Bellet and Bonnefoi, {Herv{\'e} R.} and Climent, {Miguel A.} and {Da Prada}, {Gian Antonio} and Burstein, {Harold J.} and Silvana Martino and Davidson, {Nancy E.} and Geyer, {Charles E.} and Walley, {Barbara A.} and Robert Coleman and Pierre Kerbrat and Stefan Buchholz and Ingle, {James N.} and Winer, {E. P Manuela} and Manuela Rabaglio-Poretti and Rudolf Maibach and Barbara Ruepp and Anita Giobbie-Hurder and Price, {Karen N.} and Marco Colleoni and Giuseppe Viale and Coates, {Alan S.} and Aron Goldhirsch and Gelber, {Richard D.}",
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TY - JOUR

T1 - Adjuvant ovarian suppression in premenopausal breast cancer

AU - Francis, Prudence A.

AU - Regan, Meredith M.

AU - Fleming, Gini F.

AU - Láng, István

AU - Ciruelos, Eva

AU - Bellet, Meritxell

AU - Bonnefoi, Hervé R.

AU - Climent, Miguel A.

AU - Da Prada, Gian Antonio

AU - Burstein, Harold J.

AU - Martino, Silvana

AU - Davidson, Nancy E.

AU - Geyer, Charles E.

AU - Walley, Barbara A.

AU - Coleman, Robert

AU - Kerbrat, Pierre

AU - Buchholz, Stefan

AU - Ingle, James N.

AU - Winer, E. P Manuela

AU - Rabaglio-Poretti, Manuela

AU - Maibach, Rudolf

AU - Ruepp, Barbara

AU - Giobbie-Hurder, Anita

AU - Price, Karen N.

AU - Colleoni, Marco

AU - Viale, Giuseppe

AU - Coates, Alan S.

AU - Goldhirsch, Aron

AU - Gelber, Richard D.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - BACKGROUND Suppression of ovarian estrogen production reduces the recurrence of hormonereceptor- positive early breast cancer in premenopausal women, but its value when added to tamoxifen is uncertain.METHODS We randomly assigned 3066 premenopausal women, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. The primary analysis tested the hypothesis that tamoxifen plus ovarian suppression would improve disease-free survival, as compared with tamoxifen alone. In the primary analysis, 46.7% of the patients had not received chemotherapy previously, and 53.3% had received chemotherapy and remained premenopausal.RESULTS After a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen-ovarian suppression group and 84.7% in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% confidence interval [CI], 0.66 to 1.04; P = 0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone (hazard ratio, 0.78; 95% CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5% in the tamoxifen-ovarian suppression group and 78.0% in the tamoxifen group (hazard ratio for recurrence, 0.78; 95% CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7% in the exemestane-ovarian suppression group (hazard ratio for recurrence vs. tamoxifen, 0.65; 95% CI, 0.49 to 0.87).CONCLUSIONS Adding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes. Further improvement was seen with the use of exemestane plus ovarian suppression.

AB - BACKGROUND Suppression of ovarian estrogen production reduces the recurrence of hormonereceptor- positive early breast cancer in premenopausal women, but its value when added to tamoxifen is uncertain.METHODS We randomly assigned 3066 premenopausal women, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. The primary analysis tested the hypothesis that tamoxifen plus ovarian suppression would improve disease-free survival, as compared with tamoxifen alone. In the primary analysis, 46.7% of the patients had not received chemotherapy previously, and 53.3% had received chemotherapy and remained premenopausal.RESULTS After a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen-ovarian suppression group and 84.7% in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% confidence interval [CI], 0.66 to 1.04; P = 0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone (hazard ratio, 0.78; 95% CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5% in the tamoxifen-ovarian suppression group and 78.0% in the tamoxifen group (hazard ratio for recurrence, 0.78; 95% CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7% in the exemestane-ovarian suppression group (hazard ratio for recurrence vs. tamoxifen, 0.65; 95% CI, 0.49 to 0.87).CONCLUSIONS Adding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes. Further improvement was seen with the use of exemestane plus ovarian suppression.

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