Extending aromatase-inhibitor adjuvant therapy to 10 years

P. E. Goss, J. N. Ingle, K. I. Pritchard, N. J. Robert, H. Muss, J. Gralow, K. Gelmon, T. Whelan, K. Strasser-Weippl, S. Rubin, K. Sturtz, A. C. Wolff, E. Winer, C. Hudis, A. Stopeck, J. T. Beck, Judith S Kaur, K. Whelan, D. Tu, W. R. Parulekar

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Treatment with an aromatase inhibitor for 5 years as up-front monotherapy or after tamoxifen therapy is the treatment of choice for hormone-receptor-positive early breast cancer in postmenopausal women. Extending treatment with an aromatase inhibitor to 10 years may further reduce the risk of breast-cancer recurrence. METHODS: We conducted a double-blind, placebo-controlled trial to assess the effect of the extended use of letrozole for an additional 5 years. Our primary end point was disease-free survival. RESULTS: We enrolled 1918 women. After a median follow-up of 6.3 years, there were 165 events involving disease recurrence or the occurrence of contralateral breast cancer (67 with letrozole and 98 with placebo) and 200 deaths (100 in each group). The 5-year disease-free survival rate was 95% (95% confidence interval [CI], 93 to 96) with letrozole and 91% (95% CI; 89 to 93) with placebo (hazard ratio for disease recurrence or the occurrence of contralateral breast cancer, 0.66; P = 0.01 by a two-sided log-rank test stratified according to nodal status, prior adjuvant chemotherapy, the interval from the last dose of aromatase-inhibitor therapy, and the duration of treatment with tamoxifen). The rate of 5-year overall survival was 93% (95% CI, 92 to 95) with letrozole and 94% (95% CI, 92 to 95) with placebo (hazard ratio, 0.97; P = 0.83). The annual incidence rate of contralateral breast cancer in the letrozole group was 0.21% (95% CI, 0.10 to 0.32), and the rate in the placebo group was 0.49% (95% CI, 0.32 to 0.67) (hazard ratio, 0.42; P = 0.007). Bone-related toxic effects occurred more frequently among patients receiving letrozole than among those receiving placebo, including a higher incidence of bone pain, bone fractures, and new-onset osteoporosis. No significant differences between letrozole and placebo were observed in scores on most subscales measuring quality of life. CONCLUSIONS: The extension of treatment with an adjuvant aromatase inhibitor to 10 years resulted in significantly higher rates of disease-free survival and a lower incidence of contralateral breast cancer than those with placebo, but the rate of overall survival was not higher with the aromatase inhibitor than with placebo.

Original languageEnglish (US)
Pages (from-to)209-219
Number of pages11
JournalNew England Journal of Medicine
Volume375
Issue number3
DOIs
StatePublished - Jul 21 2016

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letrozole
Aromatase Inhibitors
Placebos
Confidence Intervals
Breast Neoplasms
Disease-Free Survival
Therapeutics
Tamoxifen
Recurrence
Incidence
Survival Rate
Bone and Bones
Poisons
Bone Fractures
Adjuvant Chemotherapy
Osteoporosis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Goss, P. E., Ingle, J. N., Pritchard, K. I., Robert, N. J., Muss, H., Gralow, J., ... Parulekar, W. R. (2016). Extending aromatase-inhibitor adjuvant therapy to 10 years. New England Journal of Medicine, 375(3), 209-219. https://doi.org/10.1056/NEJMoa1604700

Extending aromatase-inhibitor adjuvant therapy to 10 years. / Goss, P. E.; Ingle, J. N.; Pritchard, K. I.; Robert, N. J.; Muss, H.; Gralow, J.; Gelmon, K.; Whelan, T.; Strasser-Weippl, K.; Rubin, S.; Sturtz, K.; Wolff, A. C.; Winer, E.; Hudis, C.; Stopeck, A.; Beck, J. T.; Kaur, Judith S; Whelan, K.; Tu, D.; Parulekar, W. R.

In: New England Journal of Medicine, Vol. 375, No. 3, 21.07.2016, p. 209-219.

Research output: Contribution to journalArticle

Goss, PE, Ingle, JN, Pritchard, KI, Robert, NJ, Muss, H, Gralow, J, Gelmon, K, Whelan, T, Strasser-Weippl, K, Rubin, S, Sturtz, K, Wolff, AC, Winer, E, Hudis, C, Stopeck, A, Beck, JT, Kaur, JS, Whelan, K, Tu, D & Parulekar, WR 2016, 'Extending aromatase-inhibitor adjuvant therapy to 10 years', New England Journal of Medicine, vol. 375, no. 3, pp. 209-219. https://doi.org/10.1056/NEJMoa1604700
Goss PE, Ingle JN, Pritchard KI, Robert NJ, Muss H, Gralow J et al. Extending aromatase-inhibitor adjuvant therapy to 10 years. New England Journal of Medicine. 2016 Jul 21;375(3):209-219. https://doi.org/10.1056/NEJMoa1604700
Goss, P. E. ; Ingle, J. N. ; Pritchard, K. I. ; Robert, N. J. ; Muss, H. ; Gralow, J. ; Gelmon, K. ; Whelan, T. ; Strasser-Weippl, K. ; Rubin, S. ; Sturtz, K. ; Wolff, A. C. ; Winer, E. ; Hudis, C. ; Stopeck, A. ; Beck, J. T. ; Kaur, Judith S ; Whelan, K. ; Tu, D. ; Parulekar, W. R. / Extending aromatase-inhibitor adjuvant therapy to 10 years. In: New England Journal of Medicine. 2016 ; Vol. 375, No. 3. pp. 209-219.
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abstract = "BACKGROUND: Treatment with an aromatase inhibitor for 5 years as up-front monotherapy or after tamoxifen therapy is the treatment of choice for hormone-receptor-positive early breast cancer in postmenopausal women. Extending treatment with an aromatase inhibitor to 10 years may further reduce the risk of breast-cancer recurrence. METHODS: We conducted a double-blind, placebo-controlled trial to assess the effect of the extended use of letrozole for an additional 5 years. Our primary end point was disease-free survival. RESULTS: We enrolled 1918 women. After a median follow-up of 6.3 years, there were 165 events involving disease recurrence or the occurrence of contralateral breast cancer (67 with letrozole and 98 with placebo) and 200 deaths (100 in each group). The 5-year disease-free survival rate was 95{\%} (95{\%} confidence interval [CI], 93 to 96) with letrozole and 91{\%} (95{\%} CI; 89 to 93) with placebo (hazard ratio for disease recurrence or the occurrence of contralateral breast cancer, 0.66; P = 0.01 by a two-sided log-rank test stratified according to nodal status, prior adjuvant chemotherapy, the interval from the last dose of aromatase-inhibitor therapy, and the duration of treatment with tamoxifen). The rate of 5-year overall survival was 93{\%} (95{\%} CI, 92 to 95) with letrozole and 94{\%} (95{\%} CI, 92 to 95) with placebo (hazard ratio, 0.97; P = 0.83). The annual incidence rate of contralateral breast cancer in the letrozole group was 0.21{\%} (95{\%} CI, 0.10 to 0.32), and the rate in the placebo group was 0.49{\%} (95{\%} CI, 0.32 to 0.67) (hazard ratio, 0.42; P = 0.007). Bone-related toxic effects occurred more frequently among patients receiving letrozole than among those receiving placebo, including a higher incidence of bone pain, bone fractures, and new-onset osteoporosis. No significant differences between letrozole and placebo were observed in scores on most subscales measuring quality of life. CONCLUSIONS: The extension of treatment with an adjuvant aromatase inhibitor to 10 years resulted in significantly higher rates of disease-free survival and a lower incidence of contralateral breast cancer than those with placebo, but the rate of overall survival was not higher with the aromatase inhibitor than with placebo.",
author = "Goss, {P. E.} and Ingle, {J. N.} and Pritchard, {K. I.} and Robert, {N. J.} and H. Muss and J. Gralow and K. Gelmon and T. Whelan and K. Strasser-Weippl and S. Rubin and K. Sturtz and Wolff, {A. C.} and E. Winer and C. Hudis and A. Stopeck and Beck, {J. T.} and Kaur, {Judith S} and K. Whelan and D. Tu and Parulekar, {W. R.}",
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T1 - Extending aromatase-inhibitor adjuvant therapy to 10 years

AU - Goss, P. E.

AU - Ingle, J. N.

AU - Pritchard, K. I.

AU - Robert, N. J.

AU - Muss, H.

AU - Gralow, J.

AU - Gelmon, K.

AU - Whelan, T.

AU - Strasser-Weippl, K.

AU - Rubin, S.

AU - Sturtz, K.

AU - Wolff, A. C.

AU - Winer, E.

AU - Hudis, C.

AU - Stopeck, A.

AU - Beck, J. T.

AU - Kaur, Judith S

AU - Whelan, K.

AU - Tu, D.

AU - Parulekar, W. R.

PY - 2016/7/21

Y1 - 2016/7/21

N2 - BACKGROUND: Treatment with an aromatase inhibitor for 5 years as up-front monotherapy or after tamoxifen therapy is the treatment of choice for hormone-receptor-positive early breast cancer in postmenopausal women. Extending treatment with an aromatase inhibitor to 10 years may further reduce the risk of breast-cancer recurrence. METHODS: We conducted a double-blind, placebo-controlled trial to assess the effect of the extended use of letrozole for an additional 5 years. Our primary end point was disease-free survival. RESULTS: We enrolled 1918 women. After a median follow-up of 6.3 years, there were 165 events involving disease recurrence or the occurrence of contralateral breast cancer (67 with letrozole and 98 with placebo) and 200 deaths (100 in each group). The 5-year disease-free survival rate was 95% (95% confidence interval [CI], 93 to 96) with letrozole and 91% (95% CI; 89 to 93) with placebo (hazard ratio for disease recurrence or the occurrence of contralateral breast cancer, 0.66; P = 0.01 by a two-sided log-rank test stratified according to nodal status, prior adjuvant chemotherapy, the interval from the last dose of aromatase-inhibitor therapy, and the duration of treatment with tamoxifen). The rate of 5-year overall survival was 93% (95% CI, 92 to 95) with letrozole and 94% (95% CI, 92 to 95) with placebo (hazard ratio, 0.97; P = 0.83). The annual incidence rate of contralateral breast cancer in the letrozole group was 0.21% (95% CI, 0.10 to 0.32), and the rate in the placebo group was 0.49% (95% CI, 0.32 to 0.67) (hazard ratio, 0.42; P = 0.007). Bone-related toxic effects occurred more frequently among patients receiving letrozole than among those receiving placebo, including a higher incidence of bone pain, bone fractures, and new-onset osteoporosis. No significant differences between letrozole and placebo were observed in scores on most subscales measuring quality of life. CONCLUSIONS: The extension of treatment with an adjuvant aromatase inhibitor to 10 years resulted in significantly higher rates of disease-free survival and a lower incidence of contralateral breast cancer than those with placebo, but the rate of overall survival was not higher with the aromatase inhibitor than with placebo.

AB - BACKGROUND: Treatment with an aromatase inhibitor for 5 years as up-front monotherapy or after tamoxifen therapy is the treatment of choice for hormone-receptor-positive early breast cancer in postmenopausal women. Extending treatment with an aromatase inhibitor to 10 years may further reduce the risk of breast-cancer recurrence. METHODS: We conducted a double-blind, placebo-controlled trial to assess the effect of the extended use of letrozole for an additional 5 years. Our primary end point was disease-free survival. RESULTS: We enrolled 1918 women. After a median follow-up of 6.3 years, there were 165 events involving disease recurrence or the occurrence of contralateral breast cancer (67 with letrozole and 98 with placebo) and 200 deaths (100 in each group). The 5-year disease-free survival rate was 95% (95% confidence interval [CI], 93 to 96) with letrozole and 91% (95% CI; 89 to 93) with placebo (hazard ratio for disease recurrence or the occurrence of contralateral breast cancer, 0.66; P = 0.01 by a two-sided log-rank test stratified according to nodal status, prior adjuvant chemotherapy, the interval from the last dose of aromatase-inhibitor therapy, and the duration of treatment with tamoxifen). The rate of 5-year overall survival was 93% (95% CI, 92 to 95) with letrozole and 94% (95% CI, 92 to 95) with placebo (hazard ratio, 0.97; P = 0.83). The annual incidence rate of contralateral breast cancer in the letrozole group was 0.21% (95% CI, 0.10 to 0.32), and the rate in the placebo group was 0.49% (95% CI, 0.32 to 0.67) (hazard ratio, 0.42; P = 0.007). Bone-related toxic effects occurred more frequently among patients receiving letrozole than among those receiving placebo, including a higher incidence of bone pain, bone fractures, and new-onset osteoporosis. No significant differences between letrozole and placebo were observed in scores on most subscales measuring quality of life. CONCLUSIONS: The extension of treatment with an adjuvant aromatase inhibitor to 10 years resulted in significantly higher rates of disease-free survival and a lower incidence of contralateral breast cancer than those with placebo, but the rate of overall survival was not higher with the aromatase inhibitor than with placebo.

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