Hormonal contraceptives and breast cancer: Clinical data.

The endocrine background of breast cancer has raised questions about the increase in risk that might bear the use of hormonal contraceptives. This has been a particular issue in the case of young women, who constitute the population of contraceptive consumers. Observational studies have been the main source of evidence, which has mainly limited to the combined estrogen-progestogen preparations, the popular pill. Studies in the 80's and 90's of the past century found a small, around a 20%, increase in risk. The translation in absolute number of excess cases has been exiguous because the prevalence of the disease is relatively small in premenopausal women. Moreover, the risk slowly seemed to disappear after 5-10 years of use. The more sophisticated analyses provided by new technologies, together with the powerful central registries in some countries, has confirmed increased risk of similar size. Recent preparations, with lower doses of estrogens and new progestogenic molecules, have not substantially modified the risk size. The impact of progestogen only alternatives, either pills or progestogen-loaded intrauterine devices, seems to be similar, but the evidence is still insufficient. Whether there is a preferential effect on histological or molecular subtypes of breast tumours is being debated yet. The data on women at higher risk, either with mutations of the BRCA1/2 genes or with familial weight, have not found specific response patterns, but the experience is still meagre. It is of interest that long-term follow up data on women who enrolled in the initial cohorts, like that of the Royal College of General Practitioners', have shown a considerable protection against cancer of the ovary (relative risk, RR 0.67), endometrium (RR 0.66), or colorectum (RR 0.81).