5-a reductase inhibitors (5-ARI) have been suggested to increase the risk of male breast cancer. The aim of this study was to study the risk of breast cancer in men on 5-ARI, in men with benign prostatic hyperplasia (BPH) not on 5-ARI, and in men without BPH.
We performed a population-based cohort study in Sweden with data from The Prescribed Drug Register, The Patient Register, and The Cancer Register. Men on 5-ARI, men on a-blockers, or men who had undergone a transurethral resection of the prostate (TUR-P) prior to or during 2006-2008 were included as exposed to BPH and a specific treatment thereof. For each exposed man, five unexposed men were selected. Risk of breast cancer was calculated in Cox proportional hazard models.
There were 124,183 exposed men and 545,293 unexposed men, and during follow-up (median 6 years), 99 men with breast cancer were diagnosed. Compared to unexposed men, men on 5-ARI had a hazard ratio (HR) of breast cancer of 0.74 (95% confidence interval (CI) 0.27-2.03), men on a-blockers had HR 1.47 (95% CI 0.73-2.95), and men with a TUR-P had HR 1.99 (95% CI 1.05-3.75).
No increased risk of breast cancer was observed for men on 5-ARI. However, the increased risk of breast cancer among men who had undergone a TUR-P, a strong indicator of BPH, suggests that the endocrine milieu conducive to BPH is associated with male breast cancer.
Cites: Cancer Causes Control. 2014 Nov;25(11):1577-8225135615
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The E-cadherin (CDH1) gene has been associated with prostate carcinogenesis. The C/A polymorphism--160 base pairs relative to the transcription start site has been shown to decrease gene transcription. We analyzed the association between this polymorphism and the risk of sporadic, familial (2 close relatives) and hereditary (3 or more close relatives) prostate cancer. We combined data from 3 population-based epidemiologic studies in Sweden encompassing altogether 1,036 prostate cancer cases and 669 controls that were genotyped for the short nucleotide polymorphism. Odds ratios with 95% confidence intervals were estimated through unconditional logistic regression. We found no significant association between the A-allele and sporadic (OR = 1.0; 95% CI = 0.8-1.2) or familial (OR = 1.4; 95% CI = 0.9-2.2) prostate cancer. In contrast, risk of hereditary cancer was increased among heterozygote CA carriers (OR = 1.7; 95% CI = 1.0-2.7) and particularly among homozygote AA carriers (OR = 2.6; 95% CI = 1.4-4.9). Our data indicate that the -160 single nucleotide polymorphism in CDH1 is a low-penetrant prostate cancer susceptibility gene that might explain a proportion of familial and notably hereditary prostate cancer.
Adherence has not been studied in male oncology populations. The aim of this study on both the prescriber and user perspectives in prostate cancer treatment was to analyse real-life prescribing patterns of anti-androgens (AA), primarily bicalutamide, and factors influencing the patients' adherence to treatment.
A nationwide clinical cohort of incident prostate cancer, PCBaSe, was linked to the Swedish Prescribed Drug Register. Men with a planned first line monotherapy AA treatment were identified; dosages and extent of off-label treatment were investigated. Cumulative incidence proportions for reasons for drug discontinuation were calculated. Factors potentially influencing adherence were explored using the medical possession ratio based on the individual prescribed daily dose.
First line monotherapy AA was planned in 4.4Â % of all incident cases and in 2.1Â % of low risk disease cases. Among 1,406 men prescribed bicalutamide, 1,109 (79Â %) received the approved daily dose of 150Â mg. Discontinuation reasons differed with disease severity. Off-label, low-dose prescription associated with age above 75Â years and disease categorised as low risk was noted in 297 men (21Â %). Sixty percent of the men adhered well, i.e. to =80Â %. Age above 75Â years and less severe disease were both negatively associated with adherence.
Patient age and tumour risk group influenced the prescriber's choice of dose, pointing to important issues for critical reflection. Possible over-treatment was noted in low risk disease. Interventions to increase adherence in older men and in men with less severe disease are worth considering after critically reviewing the appropriateness of the treatment indication, especially in the latter case.
Androgen deprivation therapy (ADT) for prostate cancer (PCa) increases risk of type 2 diabetes (T2DM); however the association between types and duration of ADT has not been fully elucidated. We examined how type and duration of ADT affects risk of T2DM. Using data from Prostate Cancer database Sweden (PCBaSe) we investigated risk of T2DM in a cohort of 34,031 men with PCa on ADT; i.e., anti-androgens (AA), orchiectomy, or gonadotropin-releasing hormone (GnRH) agonists compared to an age-matched, PCa-free comparison cohort (n?=?167,205) using multivariate Cox proportional hazard regression. T2DM was defined as a newly filled prescription for metformin, sulphonylurea, or insulin in the Prescribed Drug Register. A total of 21,874 men with PCa received GnRH agonists, 9,143 AA and 3,014 underwent orchiectomy. Risk of T2DM was increased in men in the GnRH agonists/orchiectomy group during the first 3 years of ADT [i.e., 1?-?1.5 years HR: 1.61 (95%CI: 1.36?-?1.91)], compared to PCa-free men. The risk decreased thereafter (e.g., 3?-?4 years HR: 1.17 (95% CI: 0.98?-?1.40)). Conversely, no increased risk was seen in men on AA (HR: 0.74 (95%CI: 0.65?-?0.84). The incidence of T2DM per 1,000 person-years was 10 for PCa-free men, 8 for men on AA, and 13 for men on GnRH agonists/orchiectomy. Duration of ADT has a significant impact on risk of T2DM. With the peak after three years of treatment, our data indicates that men on ADT, even for a limited period of time, such as adjuvant to radiotherapy, are at increased risk of T2DM.
Findings on the association between risk of cardiovascular disease (CVD) and the duration and type of androgen-deprivation therapy (ADT) in men with prostate cancer (PCa) are inconsistent.
By using data on filled drug prescriptions in Swedish national health care registers, we investigated the risk of CVD in a cohort of 41,362 men with PCa on ADT compared with an age-matched, PCa-free comparison cohort (n = 187,785) by use of multivariable Cox proportional hazards regression models.
From 2006 to 2012, 10,656 men were on antiandrogens (AA), 26,959 were on gonadotropin-releasing hormone (GnRH) agonists, and 3,747 underwent surgical orchiectomy. CVD risk was increased in men on GnRH agonists compared with the comparison cohort (hazard ratio [HR] of incident CVD, 1.21; 95% CI, 1.18 to 1.25; and orchiectomy: HR, 1.16; 95% CI, 1.08 to 1.25). Men with PCa on AA were at decreased risk (HR of incident CVD, 0.87; 95% CI, 0.82 to 0.91). CVD risk was highest during the first 6 months of ADT in men who experienced two or more cardiovascular events before therapy, with an HR of CVD during the first 6 months of GnRH agonist therapy of 1.91 (95% CI, 1.66 to 2.20), an HR of CVD with AA of 1.60 (95% CI, 1.24 to 2.06), and an HR of CVD with orchiectomy of 1.79 (95% CI, 1.16 to 2.76) versus the comparison cohort.
Our results support that there should be a solid indication for ADT in men with PCa so that benefit outweighs potential harm; this is of particular importance among men with a recent history of CVD.