Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial.
BACKGROUND
Tamoxifen is approved for the reduction of breast cancer risk, and raloxifene has demonstrated a reduced risk of breast cancer in trials of older women with osteoporosis.


OBJECTIVE
To compare the relative effects and safety of raloxifene and tamoxifen on the risk of developing invasive breast cancer and other disease outcomes.


METHODS
The National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene trial, a prospective, double-blind, randomized clinical trial conducted beginning July 1, 1999, in nearly 200 clinical centers throughout North America, with final analysis initiated after at least 327 incident invasive breast cancers were diagnosed. Patients were 19,747 postmenopausal women of mean age 58.5 years with increased 5-year breast cancer risk (mean risk, 4.03% [SD, 2.17%]). Data reported are based on a cutoff date of December 31, 2005.


METHODS
Oral tamoxifen (20 mg/d) or raloxifene (60 mg/d) over 5 years.


METHODS
Incidence of invasive breast cancer, uterine cancer, noninvasive breast cancer, bone fractures, thromboembolic events.


RESULTS
There were 163 cases of invasive breast cancer in women assigned to tamoxifen and 168 in those assigned to raloxifene (incidence, 4.30 per 1000 vs 4.41 per 1000; risk ratio [RR], 1.02; 95% confidence interval [CI], 0.82-1.28). There were fewer cases of noninvasive breast cancer in the tamoxifen group (57 cases) than in the raloxifene group (80 cases) (incidence, 1.51 vs 2.11 per 1000; RR, 1.40; 95% CI, 0.98-2.00). There were 36 cases of uterine cancer with tamoxifen and 23 with raloxifene (RR, 0.62; 95% CI, 0.35-1.08). No differences were found for other invasive cancer sites, for ischemic heart disease events, or for stroke. Thromboembolic events occurred less often in the raloxifene group (RR, 0.70; 95% CI, 0.54-0.91). The number of osteoporotic fractures in the groups was similar. There were fewer cataracts (RR, 0.79; 95% CI, 0.68-0.92) and cataract surgeries (RR, 0.82; 95% CI, 0.68-0.99) in the women taking raloxifene. There was no difference in the total number of deaths (101 vs 96 for tamoxifen vs raloxifene) or in causes of death.


CONCLUSIONS
Raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer and has a lower risk of thromboembolic events and cataracts but a nonstatistically significant higher risk of noninvasive breast cancer. The risk of other cancers, fractures, ischemic heart disease, and stroke is similar for both drugs.


BACKGROUND
clinicaltrials.gov Identifier: NCT00003906.
Vogel
Victor G
VG
Magee-Womens Hospital, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, Pa 15213-3221, USA. vvogel@magee.edu
Costantino
Joseph P
JP
Wickerham
D Lawrence
DL
Cronin
Walter M
WM
Cecchini
Reena S
RS
Atkins
James N
JN
Bevers
Therese B
TB
Fehrenbacher
Louis
L
Pajon
Eduardo R
ER
Wade
James L
JL
Robidoux
André
A
Margolese
Richard G
RG
James
Joan
J
Lippman
Scott M
SM
Runowicz
Carolyn D
CD
Ganz
Patricia A
PA
Reis
Steven E
SE
McCaskill-Stevens
Worta
W
Ford
Leslie G
LG
Jordan
V Craig
VC
Wolmark
Norman
N
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000517:prevention & control*; D002386:Cataract / Q000453:epidemiology; D002423:Cause of Death; D004311:Double-Blind Method; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D012306:Risk; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D013629:Tamoxifen / Q000627:therapeutic use*; D013927:Thrombosis / Q000453:epidemiology; D014594:Uterine Neoplasms / Q000453:epidemiology
D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride