Hormone replacement therapy use and variations in the risk of breast cancer.
OBJECTIVE
To determine the effect of different types and formulations of hormone replacement therapy (HRT) on the risk of breast cancer in postmenopausal women.


METHODS
Population-based case-control study.


METHODS
UK, 1988-2004.


METHODS
Women 50-75 years between 1998 and 2004.


METHODS
Breast cancer incidence to estimate the rate ratio (RR) associated with use of various HRTs over a 30-year period.


RESULTS
We identified 6347 incident cases of breast cancer that were matched with 31,516 controls. Cases were on average 61 years at diagnosis and 22% had undergone a hysterectomy. The rate of breast cancer was increased with the use of opposed estrogens in oral form (adjusted RR 1.38; 95% CI 1.27-1.49) in contrast to patch form (RR 1.08; 95% CI 0.81-1.43). This rate was similarly elevated with both continuous (RR 1.29; 95% CI 1.07-1.56) and sequential (RR 1.33; 95% CI 1.21-1.46) forms of opposed estrogen. The rate of breast cancer was not increased among exclusive users of unopposed estrogens (RR 0.97; 95% CI 0.86-1.09) or of tibolone (RR 0.86; 95% CI 0.65-1.13). Users of tibolone who had switched from opposed estrogens, however, had an elevated rate (RR 1.29; 95% CI 1.09-1.52). The rate of breast cancer increased by 25% (95% CI 20-30%) with every ten prescriptions of orally administered opposed estrogen.


CONCLUSIONS
The risk of breast cancer varies with the formulation and preparation of HRT. Opposed estrogens (progesterone-estrogen) in oral form are associated with an increased risk of breast cancer, which increases with use. Transdermal opposed estrogens, unopposed estrogens and tibolone do not increase this risk. However, this study is an observational study that carries risks of various biases, and thus the findings need to be interpreted with caution.
Opatrny
L
L
Division of Internal Medicine, Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada.
Dell'Aniello
S
S
Assouline
S
S
Suissa
S
S
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000368:Aged; D001943:Breast Neoplasms / Q000139:chemically induced*; D016022:Case-Control Studies; D020847:Estrogen Receptor Modulators / Q000009:adverse effects; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D008875:Middle Aged; D009652:Norpregnenes / Q000009:adverse effects; D016017:Odds Ratio; D011247:Pregnancy; D011374:Progesterone / Q000009:adverse effects; D011372:Progestins / Q000009:adverse effects; D012307:Risk Factors
D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; D011372:Progestins; D011374:Progesterone; C027385:tibolone