Reduced incidence of invasive breast cancer with raloxifene among women at increased coronary risk.
BACKGROUND
In the Raloxifene Use for The Heart trial, 10 101 postmenopausal women with coronary heart disease (CHD) or multiple CHD risk factors were randomly assigned to 60 mg/d raloxifene or to placebo and followed for a median of 5.6 years. Raloxifene, a selective estrogen receptor modulator, was found to reduce the risk of invasive breast cancer and vertebral fractures but not the risk of cardiovascular events. Here, we provide further details about breast cancer incidence by tumor characteristics, duration of treatment, and subgroup.


METHODS
Reported breast cancer was adjudicated by an independent committee based on medical records and pathology reports. The primary analyses used Cox proportional hazards models with time to first breast cancer as the outcome. Subgroup effects were analyzed using similar models with terms for treatment by subgroup. All statistical tests were two-sided.


RESULTS
As previously reported, raloxifene reduced the incidence of invasive breast cancer by 44% (hazard ratio [HR] = 0.56; 95% confidence interval [CI] = 0.38 to 0.83; absolute risk reduction = 1.2 invasive breast cancers per 1000 women treated for 1 year). The lower incidence of invasive breast cancer reflected a 55% lower incidence of invasive estrogen receptor (ER)-positive tumors (HR = 0.45; 95% CI = 0.28 to 0.72). However, raloxifene treatment did not reduce the incidence of noninvasive breast cancer or of invasive ER-negative breast cancer. The reduced incidence of invasive breast cancer was similar across subgroups, including those defined by age, body mass index, family history of breast cancer, prior use of postmenopausal hormones, and 5-year estimated risk of invasive breast cancer.


CONCLUSIONS
Raloxifene reduces risk of invasive ER-positive breast cancer regardless of a woman's baseline breast cancer risk but does not reduce risk of noninvasive or ER-negative breast cancers. These results confirm those of the Multiple Outcomes of Raloxifene Evaluation, a previous randomized trial among women with osteoporosis.
Grady
Deborah
D
University of California, San Francisco, and San Francisco VA Medical Center, San Francisco, CA 94115, USA. deborah.grady@ucsf.edu
Cauley
Jane A
JA
Geiger
Mary Jane
MJ
Kornitzer
Marcel
M
Mosca
Lori
L
Collins
Peter
P
Wenger
Nanette K
NK
Song
Jingli
J
Mershon
John
J
Barrett-Connor
Elizabeth
E
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control*; D003327:Coronary Disease / Q000209:etiology*; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016017:Odds Ratio; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy; D016016:Proportional Hazards Models; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D013131:Spine
D018931:Antineoplastic Agents, Hormonal; D050071:Bone Density Conservation Agents; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride