Progestins and breast cancer: an epidemiologic review

Abstract

Objective: To provide a worldwide review of all studies that have examined the relationship between progestins, as contained in both contraceptive and postmenopausal replacement therapies, and breast cancer risk. An overview of utilization patterns for progestins, as well as a review of possible biological mechanisms for progestins' action on breast tissue, are also presented.

Data identification: All major epidemiologic studies conducted since 1980 have been identified through MEDLINE searches through the published literature and personal communications with prominent researchers in the area.

Study selection: Only studies that specifically examined the effects of progestin use are discussed here; these include investigations of progestins, in combination or singularly, as the main hypothesis or a subgroup analysis.

Results: The majority of studies have examined combination estrogen and progestin products (oral contraceptives), and subgroup analyses of progestins have been impeded by low statistical power and the fact that each progestin possesses different types of pharmacological activity. Only a few studies of long-acting injectable progestins exist, confirming a general lack of specific information on the progesterone-breast cancer relationship. Investigations of the effect on breast cancer of the addition of progestins to postmenopausal replacement therapy have also produced inconsistent results.

Conclusions: To date, there is no consistent evidence of an association between progestins and breast cancer. There is need for further study, particularly of patients in potentially high-risk groups, including those with (1) extended hormone exposure before age 25 and/or first full term pregnancy and (2) exposure in the postmenopausal period.

PIP: Major epidemiologic studies since 1980 which looked at the relationship between progestins in contraceptive and postmenopausal replacement therapies and breast cancer risk were reviewed and analyzed to determine to what extent progestin use may influence breast cancer risk. Most of these studies centered on combination oral contraceptives that contain estrogen and progestin. Low statistical power restricted any subgroup analyses of progestins. Another obstacle was that the pharmacological activity of each progestin is different. Further, scientists cannot agree on the biological mechanism of progestin action on breast tissue. In addition, the link between progestins and breast cancer may actually change during and after the reproductive cycle. Just a limited number of studies on long-acting injectables had taken place which did not provide specific information on the progesterone and breast cancer association. Also, the results of studies examining the effect of adding progestins to postmenopausal replacement therapy on breast cancer were contradictory. Since no clear evidence of a relationship between progestins and breast cancer exists, scientists need to conduct further studies. These studies should concentrate on women in potentially high risk groups which include those who have been exposed extensively to hormones before 25 years of age and/or 1st full-term pregnancy, those who have been exposed postmenopausally, and nulliparous women who began menstruating when younger than 13 years old.