AuthorGoss, Paul E.
Ingle, James N.
Pritchard, Kathleen I.
Robert, Nicholas J.
Wolff, Antonio C.
Beck, J. Thaddeus
Kaur, Judith S.
Parulekar, Wendy R.
MetadataShow full item record
PublisherMASSACHUSETTS MEDICAL SOC
CitationExtending Aromatase-Inhibitor Adjuvant Therapy to 10 Years 2016, 375 (3):209 New England Journal of Medicine
JournalNew England Journal of Medicine
RightsCopyright © 2016 Massachusetts Medical Society
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractBACKGROUND 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. ( Funded by the Canadian Cancer Society and others;)
NoteJuly 21, 2016. 6 Month Embargo.
VersionFinal published version
SponsorsCanadian Cancer Society Research Institute [021039, 015469]; National Cancer Institute [CA180888, CA189953, CA180828, CA13612, CA37981, CA077202, CA180863, CA67753, CA189805, CA16116, CA180802]; Canadian Cancer Trials Group [CA077202, CA180863]; ECOG-ACRIN Cancer Research Group [CA180820, CA21115]; Novartis Pharmaceuticals; Avon Foundation; AstraZeneca; Pfizer; Roche; Amgen; Novartis; Glaxo-SmithKline; Eisai; Genomic Health; NanoString; Genentech; BioMarin
CollectionsUA Faculty Publications
- Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer.
- Authors: BIG 1-98 Collaborative Group., Mouridsen H, Giobbie-Hurder A, Goldhirsch A, Thürlimann B, Paridaens R, Smith I, Mauriac L, Forbes J, Price KN, Regan MM, Gelber RD, Coates AS
- Issue date: 2009 Aug 20
- Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17.
- Authors: 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
- Issue date: 2005 Sep 7
- Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up.
- Authors: Regan MM, Neven P, Giobbie-Hurder A, Goldhirsch A, Ejlertsen B, Mauriac L, Forbes JF, Smith I, Láng I, Wardley A, Rabaglio M, Price KN, Gelber RD, Coates AS, Thürlimann B, BIG 1-98 Collaborative Group., International Breast Cancer Study Group (IBCSG).
- Issue date: 2011 Nov
- Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and Colorectal Cancer Study Group Trial 6a.
- Authors: Jakesz R, Greil R, Gnant M, Schmid M, Kwasny W, Kubista E, Mlineritsch B, Tausch C, Stierer M, Hofbauer F, Renner K, Dadak C, Rücklinger E, Samonigg H, Austrian Breast and Colorectal Cancer Study Group.
- Issue date: 2007 Dec 19
- A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer.
- Authors: Breast International Group (BIG) 1-98 Collaborative Group., Thürlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I, Wardley A, Price KN, Goldhirsch A
- Issue date: 2005 Dec 29