Risk of breast cancer after exposure to fertility drugs: results from a large Danish cohort study.

BACKGROUND: Few epidemiologic studies have examined the association between fertility drugs and breast cancer risk, and results have been contradicting. Using data from the largest cohort of infertile women to date, the aim of this study was to examine the effects of fertility drugs on breast cancer risk overall and according to histologic subtypes. METHOD: A cohort of 54,362 women with infertility problems referred to all Danish fertility clinics between 1963 and 1998 was established. A detailed data collection, including information of type and amount of treatment, was conducted. We used case-cohort techniques to calculate rate ratios (RR) of breast cancer associated with use of five groups of fertility drugs, after adjustment for parity status. RESULTS: Three hundred thirty-one invasive breast cancers were identified in the cohort during follow-up through 1998. Analyses within cohort showed no overall increased breast cancer risk after use of gonadotrophins, clomiphene, human chorionic gonadotrophin, or gonadotrophin-releasing hormone, whereas use of progesterone increased breast cancer risk (RR, 3.36; 95% confidence interval, 1.3-8.6). For all groups of fertility drugs, no relationships with number of cycles of use or years since first use of fertility drug were found. However, gonadotrophins may have a stronger effect on breast cancer risk among nulliparous women (RR, 1.69; 95% confidence interval, 1.03-2.77). Similar risk patterns were present for ductal, lobular, and tumors of other histologies, indicating identical etiologies. CONCLUSION: The results showed no strong association between breast cancer risk and use of fertility drugs. Follow-up is, however, needed to assess long-term breast cancer risk after use of progesterone and among nulliparous women exposed to gonadotrophins.

Type specific persistence of high risk human papillomavirus (HPV) as indicator of high grade cervical squamous intraepithelial lesions in young women: population based prospective follow up study.

OBJECTIVES: To investigate the role of human papillomavirus (HPV) in the development of cervical neoplasia in women with no previous cervical cytological abnormalities; whether the presence of virus DNA predicts development of squamous intraepithelial lesion; and whether the risk of incident squamous intraepithelial lesions differs with repeated detection of the same HPV type versus repeated detection of different types. DESIGN: Population based prospective cohort study. SETTING: General population in Copenhagen, Denmark. PARTICIPANTS: 10 758 women aged 20-29 years followed up for development of cervical cytological abnormalities; 370 incident cases were detected (40 with atypical squamous cells of undetermined significance, 165 with low grade squamous intraepithelial lesions, 165 with high grade squamous intraepithelial lesions). MAIN OUTCOME MEASURES: RESULTS of cervical smear tests and cervical swabs at enrollment and at the second examination about two years later. RESULTS: Compared with women who were negative for human papillomavirus at enrollment, those with positive results had a significantly increased risk at follow up of having atypical cells (odds ratio 3.2, 95% confidence interval 1.3 to 7.9), low grade lesions (7.5, 4.8 to 11.7), or high grade lesions (25.8, 15.3 to 43.6). Similarly, women who were positive for HPV at the second examination had a strongly increased risk of low (34.3, 17.6 to 67.0) and high grade lesions (60.7, 25.5 to 144.0). For high grade lesions the risk was strongly increased if the same virus type was present at both examinations (813.0, 168.2 to 3229.2). CONCLUSIONS: Infection with human papillomavirus precedes the development of low and high grade squamous intraepithelial lesions. For high grade lesions the risk is greatest in women positive for the same type of HPV on repeated testing.