Do the dose or route of administration of norethisterone acetate as a part of hormone therapy play a role in risk of breast cancer: national-wide case-control study from Finland.

We examined the associations between various doses and routes of administration of norethisterone acetate (NETA) in estrogen-progestagen therapy (EPT) and the risk of breast cancer in Finland. All Finnish women with first invasive breast cancer diagnosed between the ages of 50-62 during 1995-2007 (n = 9,956) were identified from the Finnish Cancer Registry. For each case, 3 controls of the same age were retrieved from the Finnish Population Register. The use of estradiol+NETA-therapy by the cases and controls was traced from the national Medical Reimbursement Registry. The data were analyzed with multivariate conditional logistic regression, adjusting for parity, age at the first birth, and health care district. The continuous mode of NETA use tended to be associated with a higher rate ratio for breast cancer than the sequential use. The use of continuous "low" dose (NETA 0.5 mg + estradiol 1.0 mg) was associated with an increased rate ratio of breast cancer already in less than 3 years of use (odds ratio 1.94; 95% confidence interval 1.39-2.70) while a risk elevation for "high" dose (NETA 1.0 mg + estradiol 2.0 mg) was seen after 3 years use (1.71; 1.51-2.54). Oral and transdermal use of NETA were accompanied with comparable risks for breast cancer. In conclusion, the dose or route of administration of NETA in EPT do not modify the risks for breast cancer.