Postmenopausal hormone therapy and the risk of breast cancer in Norway

Abstract

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. What's new? Women who are considering treatment for menopausal symptoms must weigh the risks and benefits carefully, as combined estrogen-progestin therapy can significantly elevate the risk of breast cancer. But, as this study shows, not all types of estrogen-progestin therapy are created equally when it comes to breast cancer risk. Data from the Norwegian Prescription Database and the Cancer Registry of Norway shows that among women aged 45-79 years, breast cancer risk increases threefold in association with use of estradiol-norethisterone and increases almost twofold with the use of the synthetic steroid tibolone. Oral and transdermal estrogen therapies showed only moderate risk increases.