Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen

Paul E. Goss, James N. Ingle, Joseph L. Pater, Silvana Martino, Nicholas J. Robert, Hyman B. Muss, Martine J. Piccart, Monica Castiglione, Lois E. Shepherd, Kathleen I. Pritchard, Robert B. Livingston, Nancy E. Davidson, Larry Norton, Edith A. Perez, Jeffrey S. Abrams, David A. Cameron, Michael J. Palmer, Dongsheng Tu

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Abstract

Purpose: The National Cancer Institute of Canada Clinical Trials Group MA.17 trial examined the efficacy of letrozole (LET) started within 3 months of 5 years of adjuvant tamoxifen in postmenopausal hormone receptor-positive early-stage breast cancer. When the trial was unblinded, patients who received placebo (PLAC) were offered LET. Patients and Methods: This cohort analysis describes the outcomes of women assigned PLAC at the initial random assignment after unblinding. Efficacy outcomes of women who chose LET (PLAC-LET group) were compared with those who did not (PLAC-PLAC group) by the hazard ratios and by P values calculated from Cox models that adjusted for imbalances between the groups. Toxicity analyses included only events that occurred after unblinding. Results: There were 1,579 women in the PLAC-LET group (median time from tamoxifen, 2.8 years) and 804 in the PLAC-PLAC group. Patients in the PLAC-LET group were younger; had a better performance status; and were more likely to have had node-positive disease, axillary dissection, and adjuvant chemotherapy than those in the PLAC-PLAC group. At a median follow-up of 5.3 years, disease-free survival (DFS; adjusted hazard ratio [HR], 0.37; 95% CI, 0.23 to 0.61; P < .0001) and distant DFS (HR, 0.39; 95% CI, 0.20 to 0.74; P = .004) were superior in the PLAC-LET group. More self-reported new diagnoses of osteoporosis and significantly more clinical fractures occurred in the women who took LET (5.2% v 3.1%, P = .02). Conclusion: Interpretation of this cohort analysis suggests that LET improves DFS and distant DFS even when there has been a substantial period of time since the discontinuation of prior adjuvant tamoxifen.

Original languageEnglish (US)
Pages (from-to)1948-1955
Number of pages8
JournalJournal of Clinical Oncology
Volume26
Issue number12
DOIs
StatePublished - 2008
Externally publishedYes

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letrozole
Tamoxifen
Placebos
Breast Neoplasms
Therapeutics
Cohort Studies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. / Goss, Paul E.; Ingle, James N.; Pater, Joseph L.; Martino, Silvana; Robert, Nicholas J.; Muss, Hyman B.; Piccart, Martine J.; Castiglione, Monica; Shepherd, Lois E.; Pritchard, Kathleen I.; Livingston, Robert B.; Davidson, Nancy E.; Norton, Larry; Perez, Edith A.; Abrams, Jeffrey S.; Cameron, David A.; Palmer, Michael J.; Tu, Dongsheng.

In: Journal of Clinical Oncology, Vol. 26, No. 12, 2008, p. 1948-1955.

Research output: Contribution to journalArticle

Goss, PE, Ingle, JN, Pater, JL, Martino, S, Robert, NJ, Muss, HB, Piccart, MJ, Castiglione, M, Shepherd, LE, Pritchard, KI, Livingston, RB, Davidson, NE, Norton, L, Perez, EA, Abrams, JS, Cameron, DA, Palmer, MJ & Tu, D 2008, 'Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen', Journal of Clinical Oncology, vol. 26, no. 12, pp. 1948-1955. https://doi.org/10.1200/JCO.2007.11.6798
Goss, Paul E. ; Ingle, James N. ; Pater, Joseph L. ; Martino, Silvana ; Robert, Nicholas J. ; Muss, Hyman B. ; Piccart, Martine J. ; Castiglione, Monica ; Shepherd, Lois E. ; Pritchard, Kathleen I. ; Livingston, Robert B. ; Davidson, Nancy E. ; Norton, Larry ; Perez, Edith A. ; Abrams, Jeffrey S. ; Cameron, David A. ; Palmer, Michael J. ; Tu, Dongsheng. / Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 12. pp. 1948-1955.
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abstract = "Purpose: The National Cancer Institute of Canada Clinical Trials Group MA.17 trial examined the efficacy of letrozole (LET) started within 3 months of 5 years of adjuvant tamoxifen in postmenopausal hormone receptor-positive early-stage breast cancer. When the trial was unblinded, patients who received placebo (PLAC) were offered LET. Patients and Methods: This cohort analysis describes the outcomes of women assigned PLAC at the initial random assignment after unblinding. Efficacy outcomes of women who chose LET (PLAC-LET group) were compared with those who did not (PLAC-PLAC group) by the hazard ratios and by P values calculated from Cox models that adjusted for imbalances between the groups. Toxicity analyses included only events that occurred after unblinding. Results: There were 1,579 women in the PLAC-LET group (median time from tamoxifen, 2.8 years) and 804 in the PLAC-PLAC group. Patients in the PLAC-LET group were younger; had a better performance status; and were more likely to have had node-positive disease, axillary dissection, and adjuvant chemotherapy than those in the PLAC-PLAC group. At a median follow-up of 5.3 years, disease-free survival (DFS; adjusted hazard ratio [HR], 0.37; 95{\%} CI, 0.23 to 0.61; P < .0001) and distant DFS (HR, 0.39; 95{\%} CI, 0.20 to 0.74; P = .004) were superior in the PLAC-LET group. More self-reported new diagnoses of osteoporosis and significantly more clinical fractures occurred in the women who took LET (5.2{\%} v 3.1{\%}, P = .02). Conclusion: Interpretation of this cohort analysis suggests that LET improves DFS and distant DFS even when there has been a substantial period of time since the discontinuation of prior adjuvant tamoxifen.",
author = "Goss, {Paul E.} and Ingle, {James N.} and Pater, {Joseph L.} and Silvana Martino and Robert, {Nicholas J.} and Muss, {Hyman B.} and Piccart, {Martine J.} and Monica Castiglione and Shepherd, {Lois E.} and Pritchard, {Kathleen I.} and Livingston, {Robert B.} and Davidson, {Nancy E.} and Larry Norton and Perez, {Edith A.} and Abrams, {Jeffrey S.} and Cameron, {David A.} and Palmer, {Michael J.} and Dongsheng Tu",
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T1 - Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen

AU - Goss, Paul E.

AU - Ingle, James N.

AU - Pater, Joseph L.

AU - Martino, Silvana

AU - Robert, Nicholas J.

AU - Muss, Hyman B.

AU - Piccart, Martine J.

AU - Castiglione, Monica

AU - Shepherd, Lois E.

AU - Pritchard, Kathleen I.

AU - Livingston, Robert B.

AU - Davidson, Nancy E.

AU - Norton, Larry

AU - Perez, Edith A.

AU - Abrams, Jeffrey S.

AU - Cameron, David A.

AU - Palmer, Michael J.

AU - Tu, Dongsheng

PY - 2008

Y1 - 2008

N2 - Purpose: The National Cancer Institute of Canada Clinical Trials Group MA.17 trial examined the efficacy of letrozole (LET) started within 3 months of 5 years of adjuvant tamoxifen in postmenopausal hormone receptor-positive early-stage breast cancer. When the trial was unblinded, patients who received placebo (PLAC) were offered LET. Patients and Methods: This cohort analysis describes the outcomes of women assigned PLAC at the initial random assignment after unblinding. Efficacy outcomes of women who chose LET (PLAC-LET group) were compared with those who did not (PLAC-PLAC group) by the hazard ratios and by P values calculated from Cox models that adjusted for imbalances between the groups. Toxicity analyses included only events that occurred after unblinding. Results: There were 1,579 women in the PLAC-LET group (median time from tamoxifen, 2.8 years) and 804 in the PLAC-PLAC group. Patients in the PLAC-LET group were younger; had a better performance status; and were more likely to have had node-positive disease, axillary dissection, and adjuvant chemotherapy than those in the PLAC-PLAC group. At a median follow-up of 5.3 years, disease-free survival (DFS; adjusted hazard ratio [HR], 0.37; 95% CI, 0.23 to 0.61; P < .0001) and distant DFS (HR, 0.39; 95% CI, 0.20 to 0.74; P = .004) were superior in the PLAC-LET group. More self-reported new diagnoses of osteoporosis and significantly more clinical fractures occurred in the women who took LET (5.2% v 3.1%, P = .02). Conclusion: Interpretation of this cohort analysis suggests that LET improves DFS and distant DFS even when there has been a substantial period of time since the discontinuation of prior adjuvant tamoxifen.

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