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N Engl J Med. 2016 Jul 21;375(3):209-19. doi: 10.1056/NEJMoa1604700. Epub 2016 Jun 5.

Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years.

Author information

1
From the Massachusetts General Hospital Cancer Center, Avon International Breast Cancer Research Program (P.E.G.), Harvard Medical School (P.E.G., E.W.), and Dana-Farber Cancer Institute (E.W.), Boston; the Department of Oncology, Mayo Clinic, Rochester, MN (J.N.I., J.S.K.); Sunnybrook Odette Cancer Centre, Toronto (K.I.P.), British Columbia Cancer Agency, Vancouver (K.G.), Canadian Cancer Trials Group, Queen's University, Kingston, ON (K.W., D.T., W.R.P.), Department of Oncology, McMaster University, Hamilton, ON (T.W.), and Dalhousie University Faculty of Medicine, Moncton Hospital, Moncton, NB (S.R.) - all in Canada; Virginia Cancer Specialists-US Oncology Network, Fairfax (N.J.R.); University of North Carolina-Lineberger Comprehensive Cancer Center, Chapel Hill (H.M.); University of Washington School of Medicine, Seattle (J.G.); Center of Oncology and Hematology, Wilheminen Hospital, Vienna (K.S.-W.); Colorado Cancer Research Program, Denver (K.S.); Johns Hopkins Kimmel Cancer Center, Baltimore (A.C.W.); Memorial Sloan Kettering Cancer Center, New York (C.H.); University of Arizona, Tucson (A.S.); and Highlands Oncology Group, Fayetteville, AR (J.T.B.).

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; ClinicalTrials.gov numbers, NCT00003140 and NCT00754845.).

PMID:
27264120
PMCID:
PMC5024713
DOI:
10.1056/NEJMoa1604700
[Indexed for MEDLINE]
Free PMC Article

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