Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen.
OBJECTIVE
To conduct meta-analyses of randomized trials of aromatase inhibitors (AIs) compared with tamoxifen either as initial monotherapy (cohort 1) or after 2 to 3 years of tamoxifen (cohort 2).


METHODS
Data submitted to the Early Breast Cancer Trialists' Collaborative Group were used in separate meta-analyses of two cohorts. Primary analyses involve postmenopausal women with tumors reported to be estrogen receptor positive. Log-rank P values are two-sided.


RESULTS
Cohort 1 comprised 9,856 patients with a mean of 5.8 years of follow-up. At 5 years, AI therapy was associated with an absolute 2.9% (SE = 0.7%) decrease in recurrence (9.6% for AI v 12.6% for tamoxifen; 2P < .00001) and a nonsignificant absolute 1.1% (SE = 0.5%) decrease in breast cancer mortality (4.8% for AI v 5.9% for tamoxifen; 2P = .1). Cohort 2 comprised 9,015 patients with a mean of 3.9 years of follow-up. At 3 years from treatment divergence (ie, approximately 5 years after starting hormonal treatment), AI therapy was associated with an absolute 3.1% (SE = 0.6%) decrease in recurrence (5.0% for AI v 8.1% for tamoxifen since divergence; 2P < .00001) and an absolute 0.7% (SE = 0.3%) decrease in breast cancer mortality (1.7% for AI v 2.4% for tamoxifen since divergence; 2P = .02). There was no convincing heterogeneity in the proportional recurrence reduction with respect to age, nodal status, tumor grade, or progesterone receptor status and no indication of an increase in nonbreast deaths with AIs in either cohort. CONCLUSION AIs produce significantly lower recurrence rates compared with tamoxifen, either as initial monotherapy or after 2 to 3 years of tamoxifen. Additional follow-up will provide clearer information on long-term survival.
Dowsett
Mitch
M
Academic Department of Biochemistry, Royal Marsden Hospital, London, United Kingdom. mitch.dowsett@icr.ac.uk
Cuzick
Jack
J
Ingle
Jim
J
Coates
Alan
A
Forbes
John
J
Bliss
Judith
J
Buyse
Marc
M
Baum
Michael
M
Buzdar
Aman
A
Colleoni
Marco
M
Coombes
Charles
C
Snowdon
Claire
C
Gnant
Michael
M
Jakesz
Raimund
R
Kaufmann
Manfred
M
Boccardo
Francesco
F
Godwin
Jon
J
Davies
Christina
C
Peto
Richard
R
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D013629:Tamoxifen / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D013629:Tamoxifen