Author
Goss, Paul E.Ingle, James N.
Pritchard, Kathleen I.
Robert, Nicholas J.
Muss, Hyman
Gralow, Julie
Gelmon, Karen
Whelan, Tim
Strasser-Weippl, Kathrin
Rubin, Sheldon
Sturtz, Keren
Wolff, Antonio C.
Winer, Eric
Hudis, Clifford
Stopeck, Alison
Beck, J. Thaddeus
Kaur, Judith S.
Whelan, Kate
Tu, Dongsheng
Parulekar, Wendy R.
Affiliation
Univ ArizonaIssue Date
2016-07-21
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MASSACHUSETTS MEDICAL SOCCitation
Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years 2016, 375 (3):209 New England Journal of MedicineJournal
New England Journal of MedicineRights
Copyright © 2016 Massachusetts Medical Society.Collection Information
This 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 repository@u.library.arizona.edu.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. ( Funded by the Canadian Cancer Society and others;)Note
July 21, 2016. 6 Month Embargo.ISSN
0028-47931533-4406
PubMed ID
27264120Version
Final published versionSponsors
Canadian 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; BioMarinAdditional Links
http://www.nejm.org/doi/10.1056/NEJMoa1604700ae974a485f413a2113503eed53cd6c53
10.1056/NEJMoa1604700
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