Breast cancer and use of rauwolfia and other antihypertensive agents in hypertensive patients: a nationwide case-control study in Finland.

Two nationwide registers, the Finnish Cancer Registry and a register of persons entitled to free drugs for hypertension, were linked in a case-control study of the association of breast cancer and use of rauwolfia. Cases were all hypertensive patients in whom breast cancer was diagnosed in 1973. To test the association specifically with rauwolfia, controls were hypertensive women matched with the cases for age and geographic area and approximately matched for duration of treatment for hypertension. There were 109 case-control pairs. Use of any physician-prescribed drugs during the year prior to diagnosis of breast cancer was ascertained from original prescriptions. In the first set of analyses the patients were classified according to the drug used during most days of the year ("main antihypertensive agent"). In the second set a person qualified as a user of the respective drug regardless of the amount taken. The relative risks in the use of rauwolfia, methyldopa, another synthetic antihypertensive or a diuretic as main antihypertensive agent all ranged between 0.90 and 1.11. The results based on use of a drug in any amount were similar. Next, pairs in which duration of treatment for hypertension was different for cases and controls were excluded. The relative risk associated with use of rauwolfia as main antihypertensive agent then increased from 1.00 to 1.30 and the risk associated with use of any amount of rauwolfia from 1.16 to 2.14. Simultaneously, the relative risk in the use of digitalis was raised from 1.33 to 2.67 and of nitroglycerin from 1.00 to 1.71. Cases also used more types of antihypertensive agents simultaneously than controls. There was no association between rauwolfia-use and breast cancer in analyses limited to pairs in which neither case nor control used digitalis. Thus, there was not a consistent drug-specific association between rauwolfia-use and breast cancer in hypertensive patients. An underlying association of hypertension, heart disease or its treatment (digitalis) and breast cancer may have confounded some of the results of this and earlier studies. In conclusion, it is unlikely that use of rauwolfia increases the risk of breast cancer.