Postmenopausal hormone therapy and the risk of breast cancer in Norway.
There is convincing evidence that combined estrogen-progestin therapy (EPT) increases the risk of breast cancer. However, the effect of different formulations, preparations and routes of administration is largely unknown. Estrogen only-therapy (ET) is, in general, not associated or weakly associated with breast cancer risk. We investigated the effect of hormone therapy (HT) with ET, EPT, and tibolone on risk of invasive breast cancer. Information on HT use was obtained from the Norwegian Prescription Database, and breast cancer incidence from the Cancer Registry of Norway. Poisson regression was used to estimate the incidence rate ratios (RR). We analyzed data from 686,614 Norwegian women, aged 45-79 years in January 2004, followed until December 2008, of whom 178,383 (26%) were prescribed HT. During the average 4.8 years of follow-up, 7,910 invasive breast cancers were registered. Compared with nonusers, current users of estradiol-norethisterone acetate (NETA)(EPT) had a RR of 2.74 (95% CI: 2.55-2.95). Users of the high dose estradiol-NETA formulation Kliogest(®) had a RR of 3.26 (95% CI: 2.84-3.73), while users of the low dose Activelle(®) had a RR of 2.76 (95% CI: 2.51-3.04). Current users of tibolone had a RR of 1.91 (95% CI: 1.61-2.28). Current users of ET with oral or transdermal estradiol had a RR of 1.40 (95% CI: 1.16-1.68), and 1.40 (95% CI: 1.00-1.95), respectively. The increased incidence rates approximates one extra invasive breast cancer case diagnosed for every 259 women using estradiol-NETA for one year, and one extra case for every 475 women using tibolone. In conclusion, use of estradiol-NETA and tibolone preparations is associated with an increased breast cancer risk.
Cancer Registry of Norway, Oslo, Norway.|Women and Children's Division, National Advisory Unit for Women's Health, Oslo University Hospital, Oslo, Norway.
Marta
M
Román
Department of Pharmacoepidemiology, Norwegian Institute of Public Health, Oslo, Norway.
Solveig
S
Sakshaug
Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway.
Sidsel
S
Graff-Iversen
Women and Children's Division, National Advisory Unit for Women's Health, Oslo University Hospital, Oslo, Norway.
Siri
S
Vangen
Cancer Registry of Norway, Oslo, Norway.|Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, the Arctic University of Norway, Tromsø, Norway.|Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Department of Genetic Epidemiology, Folkhälsan Research Center, Helsinki, Finland.
Elisabete
E
Weiderpass
Cancer Registry of Norway, Oslo, Norway.|Department of Preventive Medicine, University of Southern California, Los Angeles, CA.
Giske
G
Ursin
Cancer Registry of Norway, Oslo, Norway.|Oslo and Akershus University College of Applied Sciences, Faculty of Health Science, Oslo, Norway.
Solveig
S
Hofvind
D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology*; D004338:Drug Combinations; D004958:Estradiol / Q000009:adverse effects; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004967:Estrogens / Q000009:adverse effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000009:adverse effects; D009652:Norpregnenes / Q000009:adverse effects; D012306:Risk
D004338:Drug Combinations; D004967:Estrogens; D009652:Norpregnenes; C418365:estradiol, norethindrone drug combination; D004958:Estradiol; C027385:tibolone; D009640:Norethindrone
breast neoplasms; estrogen; female; hormonal therapy; progestin; tibolone