Long-term effects of insulin glargine on the risk of breast cancer.

AIMS/HYPOTHESIS: There have been growing concerns regarding the long-term effects of insulin glargine (A21Gly,B31Arg,B32Arg human insulin) on the risk of breast cancer. METHODS: We used the UK's General Practice Research Database (GPRD) to identify a cohort of women aged 40 years or over with type 2 diabetes, treated with insulin during 2002-2006 and followed until the first breast cancer diagnosis or 31 December 2009. After the users of insulin glargine had been matched with users of other insulins on age, calendar time and duration of prior insulin use, the HR of breast cancer associated with insulin glargine use was estimated using a Cox proportional hazards model, adjusted for known risk factors for breast cancer. RESULTS: The cohort comprised 15,227 women, including 4,579 glargine users and 10,648 users of other insulins, of which 246 developed breast cancer during up to 8 years follow-up (incidence rate 4.1 per 1,000 per year). Insulin glargine use was not associated with an increased risk of breast cancer during the first 5 years of use (HR 0.9; 95% CI 0.7-1.3). The risk tended to increase after 5 years (HR 1.8; 95% CI 0.8-4.0), and significantly so for the women who had been on insulin before starting glargine (HR 2.7; 95% CI 1.1-6.5). CONCLUSIONS/INTERPRETATION: The risk of breast cancer in women with type 2 diabetes is not increased during the first 5 years of insulin glargine use. However, longer-term use may increase this risk, particularly in women with longstanding use of insulin before starting insulin glargine.

Use of tamoxifen and aromatase inhibitors in a large population-based cohort of women with breast cancer.

BACKGROUND: Non-compliance with oral treatment in oncology is an emerging health issue. For breast cancer (BC) patients, few data are available on compliance and persistence to tamoxifen in younger women and to aromatase inhibitors (AIs) as compared with tamoxifen in older women. METHODS: We constituted a cohort of 13,479 women with BC who received at least one prescription of tamoxifen or AI between 1998 and 2008, in the United Kingdom General Practice Research Database. Days covered by medication and treatment discontinuation were studied. Time to treatment discontinuation was calculated using Kaplan-Meier estimates. RESULTS: Overall, 18.9% (95% CI: 15.1-23.0) of women on AIs as compared with 31.0% (95% CI: 29.6-32.2) of women on tamoxifen had discontinued their treatments within the first 5 years (P<0.001). This rate raised to 50.7% (95% CI: 43.0-57.9) among the 416 women under 40 years receiving tamoxifen as initial hormonal therapy. Among older women, treatment discontinuation was less frequent for AIs as compared with tamoxifen (P<0.001). Among women on AI therapy, 14% of them (n=374) had switched treatments. CONCLUSION: Among older women, the real-life patterns of use of AI show high rates of compliance. In younger women, tamoxifen is prematurely discontinued for half of patients.

Hormone replacement therapy and the risk of venous thromboembolism: a population-based study.

SUMMARY BACKGROUND: Hormone replacement therapy (HRT) using oral estrogen alone or combined with a progestogen is associated with an increased risk of venous thromboembolism (VTE) in postmenopausal women. This risk may differ for tibolone and transdermal HRT. METHODS: Among the United Kingdom's General Practice Research Database, we identified the cohort of all women aged 50-79 between 1 January 1987 and 1 March 2008. Using a nested case-control approach, all incident cases of VTE occurring during the study period were identified and matched with up to 10 controls selected from the cohort members. Rate ratios (RR) of VTE with current use of tibolone, transdermal and oral HRT were estimated using conditional logistic regression. RESULTS: The cohort of 955 582 postmenopausal women included 23 505 cases of VTE matched with 231 562 controls. The risk of VTE was not increased with current use of transdermal estrogen alone (RR 1.01; 95% CI, 0.89-1.16) or combined with a progestogen (RR 0.96; 95% CI, 0.77-1.20), or with current use of tibolone (RR 0.92; 95% CI: 0.77-1.10), relative to non-use. On the other hand, the risk was increased with current use of oral estrogen (RR 1.49; 95% CI, 1.37-1.63) and oral estrogen-progestogen (RR 1.54; 95% CI, 1.44-1.65), and increased with estrogen dosage. The risks with oral formulations were particularly elevated during the first year of use but disappeared 4 months after discontinuation. CONCLUSION: Transdermal HRT and tibolone were not associated with an increased risk of VTE in postmenopausal women.

Hormone replacement therapy use and variations in the risk of breast cancer.

OBJECTIVE: To determine the effect of different types and formulations of hormone replacement therapy (HRT) on the risk of breast cancer in postmenopausal women. DESIGN: Population-based case-control study. SETTING: UK, 1988-2004. PARTICIPANTS: Women 50-75 years between 1998 and 2004. MAIN OUTCOME MEASURES: Breast cancer incidence to estimate the rate ratio (RR) associated with use of various HRTs over a 30-year period. RESULTS: We identified 6347 incident cases of breast cancer that were matched with 31,516 controls. Cases were on average 61 years at diagnosis and 22% had undergone a hysterectomy. The rate of breast cancer was increased with the use of opposed estrogens in oral form (adjusted RR 1.38; 95% CI 1.27-1.49) in contrast to patch form (RR 1.08; 95% CI 0.81-1.43). This rate was similarly elevated with both continuous (RR 1.29; 95% CI 1.07-1.56) and sequential (RR 1.33; 95% CI 1.21-1.46) forms of opposed estrogen. The rate of breast cancer was not increased among exclusive users of unopposed estrogens (RR 0.97; 95% CI 0.86-1.09) or of tibolone (RR 0.86; 95% CI 0.65-1.13). Users of tibolone who had switched from opposed estrogens, however, had an elevated rate (RR 1.29; 95% CI 1.09-1.52). The rate of breast cancer increased by 25% (95% CI 20-30%) with every ten prescriptions of orally administered opposed estrogen. CONCLUSIONS: The risk of breast cancer varies with the formulation and preparation of HRT. Opposed estrogens (progesterone-estrogen) in oral form are associated with an increased risk of breast cancer, which increases with use. Transdermal opposed estrogens, unopposed estrogens and tibolone do not increase this risk. However, this study is an observational study that carries risks of various biases, and thus the findings need to be interpreted with caution.