Efficacy of letrozole extended adjuvant therapy according to estrogen receptor and progesterone receptor status of the primary tumor: National Cancer Institute of Canada Clinical Trials Group MA.17

Paul E. Goss, James N. Ingle, Silvana Martino, Nicholas J. Robert, Hyman B. Muss, Martine J. Piccart, Monica Castiglione, Dongsheng Tu, 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, Joseph L. Pater

Research output: Contribution to journalArticle

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Abstract

Purpose: Controversy exists regarding estrogen (ER) and progesterone (PgR) receptor expression on efficacy of adjuvant endocrine therapy. In the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial, the benefit of anastrozole over tamoxifen was substantially greater in ER+/PgR- than ER+/PgR+ tumors. In BIG 1-98 (Breast International Group), the benefits of letrozole over tamoxifen were the same in ER+ tumors irrespective of PgR. MA.17 randomized postmenopausal women after 5 years of tamoxifen, to letrozole or placebo. We present outcomes according to tumor receptor status. Patients and Methods: Disease-free survival (DFS) and other outcomes were assessed in subgroups by ER and PgR status using Cox's proportional hazards model, adjusting for nodal status and prior adjuvant chemotherapy. Results: The DFS hazard ratio (HR) for letrozole versus placebo in ER+/PgR+ tumors (N = 3,809) was 0.49 (95% CI, 0.36 to 0.67) versus 1.21 (95% CI, 0.63 to 2.34) in ER+/PgR- tumors (n = 636). ER+/PgR+ letrozole patients experienced significant benefit in distant DFS (DDFS; HR = 0.53; 95% CI, 0.35 to 0.80) and overall survival (OS; HR = 0.58; 95% CI, 0.37 to 0.90). A statistically significant difference in treatment effect between ER+/PgR+ and ER+/PgR- subgroups for DFS was observed (P = .02), but not for DDFS (P = .06) or OS (P = .09). Conclusion: These results suggest greater benefit for letrozole in DFS, DDFS, and OS in patients with ER+/PgR+ tumors, implying greater activity of letrozole in tumors with a functional ER. However, because this is a subset analysis and receptors were not measured centrally, we caution against using these results for clinical decision making.

Original languageEnglish (US)
Pages (from-to)2006-2011
Number of pages6
JournalJournal of Clinical Oncology
Volume25
Issue number15
DOIs
StatePublished - May 20 2007
Externally publishedYes

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letrozole
National Cancer Institute (U.S.)
Progesterone Receptors
Estrogen Receptors
Canada
Estrogens
Progesterone
Clinical Trials
Neoplasms
Disease-Free Survival
Tamoxifen
Therapeutics
Placebos

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Efficacy of letrozole extended adjuvant therapy according to estrogen receptor and progesterone receptor status of the primary tumor : National Cancer Institute of Canada Clinical Trials Group MA.17. / Goss, Paul E.; Ingle, James N.; Martino, Silvana; Robert, Nicholas J.; Muss, Hyman B.; Piccart, Martine J.; Castiglione, Monica; Tu, Dongsheng; 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.; Pater, Joseph L.

In: Journal of Clinical Oncology, Vol. 25, No. 15, 20.05.2007, p. 2006-2011.

Research output: Contribution to journalArticle

Goss, PE, Ingle, JN, Martino, S, Robert, NJ, Muss, HB, Piccart, MJ, Castiglione, M, Tu, D, Shepherd, LE, Pritchard, KI, Livingston, RB, Davidson, NE, Norton, L, Perez, EA, Abrams, JS, Cameron, DA, Palmer, MJ & Pater, JL 2007, 'Efficacy of letrozole extended adjuvant therapy according to estrogen receptor and progesterone receptor status of the primary tumor: National Cancer Institute of Canada Clinical Trials Group MA.17', Journal of Clinical Oncology, vol. 25, no. 15, pp. 2006-2011. https://doi.org/10.1200/JCO.2006.09.4482
Goss, Paul E. ; Ingle, James N. ; Martino, Silvana ; Robert, Nicholas J. ; Muss, Hyman B. ; Piccart, Martine J. ; Castiglione, Monica ; Tu, Dongsheng ; 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. ; Pater, Joseph L. / Efficacy of letrozole extended adjuvant therapy according to estrogen receptor and progesterone receptor status of the primary tumor : National Cancer Institute of Canada Clinical Trials Group MA.17. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 15. pp. 2006-2011.
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abstract = "Purpose: Controversy exists regarding estrogen (ER) and progesterone (PgR) receptor expression on efficacy of adjuvant endocrine therapy. In the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial, the benefit of anastrozole over tamoxifen was substantially greater in ER+/PgR- than ER+/PgR+ tumors. In BIG 1-98 (Breast International Group), the benefits of letrozole over tamoxifen were the same in ER+ tumors irrespective of PgR. MA.17 randomized postmenopausal women after 5 years of tamoxifen, to letrozole or placebo. We present outcomes according to tumor receptor status. Patients and Methods: Disease-free survival (DFS) and other outcomes were assessed in subgroups by ER and PgR status using Cox's proportional hazards model, adjusting for nodal status and prior adjuvant chemotherapy. Results: The DFS hazard ratio (HR) for letrozole versus placebo in ER+/PgR+ tumors (N = 3,809) was 0.49 (95{\%} CI, 0.36 to 0.67) versus 1.21 (95{\%} CI, 0.63 to 2.34) in ER+/PgR- tumors (n = 636). ER+/PgR+ letrozole patients experienced significant benefit in distant DFS (DDFS; HR = 0.53; 95{\%} CI, 0.35 to 0.80) and overall survival (OS; HR = 0.58; 95{\%} CI, 0.37 to 0.90). A statistically significant difference in treatment effect between ER+/PgR+ and ER+/PgR- subgroups for DFS was observed (P = .02), but not for DDFS (P = .06) or OS (P = .09). Conclusion: These results suggest greater benefit for letrozole in DFS, DDFS, and OS in patients with ER+/PgR+ tumors, implying greater activity of letrozole in tumors with a functional ER. However, because this is a subset analysis and receptors were not measured centrally, we caution against using these results for clinical decision making.",
author = "Goss, {Paul E.} and Ingle, {James N.} and Silvana Martino and Robert, {Nicholas J.} and Muss, {Hyman B.} and Piccart, {Martine J.} and Monica Castiglione and Dongsheng Tu 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 Pater, {Joseph L.}",
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T1 - Efficacy of letrozole extended adjuvant therapy according to estrogen receptor and progesterone receptor status of the primary tumor

T2 - National Cancer Institute of Canada Clinical Trials Group MA.17

AU - Goss, Paul E.

AU - Ingle, James N.

AU - Martino, Silvana

AU - Robert, Nicholas J.

AU - Muss, Hyman B.

AU - Piccart, Martine J.

AU - Castiglione, Monica

AU - Tu, Dongsheng

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 - Pater, Joseph L.

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N2 - Purpose: Controversy exists regarding estrogen (ER) and progesterone (PgR) receptor expression on efficacy of adjuvant endocrine therapy. In the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial, the benefit of anastrozole over tamoxifen was substantially greater in ER+/PgR- than ER+/PgR+ tumors. In BIG 1-98 (Breast International Group), the benefits of letrozole over tamoxifen were the same in ER+ tumors irrespective of PgR. MA.17 randomized postmenopausal women after 5 years of tamoxifen, to letrozole or placebo. We present outcomes according to tumor receptor status. Patients and Methods: Disease-free survival (DFS) and other outcomes were assessed in subgroups by ER and PgR status using Cox's proportional hazards model, adjusting for nodal status and prior adjuvant chemotherapy. Results: The DFS hazard ratio (HR) for letrozole versus placebo in ER+/PgR+ tumors (N = 3,809) was 0.49 (95% CI, 0.36 to 0.67) versus 1.21 (95% CI, 0.63 to 2.34) in ER+/PgR- tumors (n = 636). ER+/PgR+ letrozole patients experienced significant benefit in distant DFS (DDFS; HR = 0.53; 95% CI, 0.35 to 0.80) and overall survival (OS; HR = 0.58; 95% CI, 0.37 to 0.90). A statistically significant difference in treatment effect between ER+/PgR+ and ER+/PgR- subgroups for DFS was observed (P = .02), but not for DDFS (P = .06) or OS (P = .09). Conclusion: These results suggest greater benefit for letrozole in DFS, DDFS, and OS in patients with ER+/PgR+ tumors, implying greater activity of letrozole in tumors with a functional ER. However, because this is a subset analysis and receptors were not measured centrally, we caution against using these results for clinical decision making.

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