The risk for breast cancer is not evidently increased in women with hyperprolactinemia

Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Pituitary (Impact Factor: 3.2). 12/2009; 13(3):195-8. DOI: 10.1007/s11102-009-0214-y
Source: PubMed


The question has been raised whether hyperprolactinemia in humans is associated with an excess risk for breast cancer. We aimed to assess the risk of breast cancer in a previously defined large cohort of patients treated for idiopathic hyperprolactinemia or prolactinomas. Based on the pattern of drug prescriptions we identified 11,314 subjects in the PHARMO network with at least one dispensing of dopamine agonists between 1996 and 2006. Of these, 1,607 subjects were considered to have dopamine agonist-treated hyperprolactinemia based on the prescribing pattern. For the present analysis, we included only women (n = 1,342). Patients with breast cancer were identified by hospital discharge codes. Data on breast cancer incidence in the Netherlands were derived from the Dutch cancer registry. Standardized mortality ratio (SMR) was the measure of outcome to assess the association between hyperprolactinemia and breast cancer. The 1,342 patients accounted for a total of 6,576 person years. Eight patients with breast cancer during follow-up were identified. Indirect standardization with incidence proportions from the general Dutch population revealed a 7.47 expected cases. The calculated SMR for breast cancer risk in patients treated hyperprolactinemia was 1.07 (95% confidence interval 0.50-2.03). In conclusion, there is no clear evidence for increased breast cancer risk in female patients treated for either idiopathic hyperprolactinemia or prolactinomas. The uncertainty about the exact risk that is due to the relatively low number of breast cancer cases, should be overcome by pooling results in a future meta-analysis.

Download full-text


Available from: Johannes A Romijn, Dec 31, 2013
  • Source
    • "In other patients with hysterectomy or hormone replacement therapy, risperidone also can significantly relieve patient's hot flushes in 2 to 3 days without apparent side effects, and the patent has been issued by the United States in 2010 [32]. Although risperidone has been reported to induce hyperprolactinemia [71], [72], it has been reported that the risk for breast cancer is not evidently increased in women with hyperprolactinemia [73]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Tamoxifen has long been used and still is the most commonly used endocrine therapy for treatment of both early and advanced estrogen receptor-positive breast cancer in pre- and post-menopause women. Tamoxifen exerts its cytotoxic effect primarily through cytostasis which is associated with the accumulation of cells in the G0/G1 phase of the cell cycle. Apoptotic activity can also be exerted by tamoxifen which involves cleavage of caspase 9, caspase 7, caspase 3, and poly-ADP-ribose polymerase (PARP). Down-regulation of anti-apoptotic proteins Bcl-2 and Bcl-xL and up-regulation of pro-apoptotic proteins Bax and Bak have also been observed. In addition, stress response protein of GRP 94 and GRP 78 have also been induced by tamoxifen in our study. However, side effects occur during tamoxifen treatment in breast cancer patients. Researching into combination regimen of tamoxifen and drug(s) that relieves tamoxifen-induced hot flushes is important, because drug interactions may decrease tamoxifen efficacy. Risperidone has been shown to be effective in reducing or eliminating hot flushes on women with hormonal variations. In this present study, we demonstrated that combination of tamoxifen with risperidone did not interfered tamoxifen-induced cytotoxic effects in both in vitro and in vivo models, while fluoxetine abrogated the effects of tamoxifen. This is the first paper suggesting the possibility of combination treatment of tamoxifen with risperidone in breast cancer patients, providing a conceivable resolution of tamoxifen-induced side effects without interfering the efficacy of tamoxifen against breast cancer.
    Full-text · Article · Jun 2014 · PLoS ONE
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Experimental evidence indicates that prolactin might play a role in tumorigenesis of several human cancers, but data on cancer risk in hyperprolactinemia patients are sparse. The aim of this study was to investigate cancer risk in hyperprolactinemia patients. Design A population-based matched cohort study in Sweden. The hyperprolactinemia cohort consisted of patients hospitalized for hyperprolactinemia from 1987 to 1995 identified in the National Patient Register (n=585) and a hospital cohort of prolactinoma patients at Karolinska University Hospital (n=384). For each patient, ten matched individuals were identified via the Register of Population. Cancer occurrence was ascertained via the Swedish Cancer Registry. Hazard ratios (HRs) were estimated by Cox proportional hazards regression. Seventy-three malignant tumors were identified in the hyperprolactinemia patients and 660 tumors in the comparison group (HR 1.31; 95% confidence interval (CI): 1.02-1.68), mainly attributed to an increased risk of upper gastrointestinal cancer in both males and females (HR 3.69; 95% CI: 1.70-8.03) and hematopoietic cancer in females (HR 3.51; 95% CI: 1.06-11.6). Twelve breast cancers occurred in the female patients, corresponding to an HR of 1.09 (95% CI: 0.60-1.99). Prostate cancer risk in hyperprolactinemia men was reduced (HR 0.40; 95% CI: 0.16-0.99). An increased overall cancer risk was found in hyperprolactinemia patients, but no increased risk of breast cancer in women and a reduced risk of prostate cancer in men. These findings warrant further investigations and to be confirmed in larger studies but may indicate the importance of an active treatment strategy and follow-up of hyperprolactinemia patients.
    Preview · Article · May 2011 · European Journal of Endocrinology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Antipsychotic medications are a potential cause of hyperprolactinaemia and may be implicated in the development of pituitary adenomas. This review examines the effect of different antipsychotic medications on prolactin and sexual function, and provides practical guidelines for investigation and management of antipsychotic-induced hyperprolactinaemia. Literature review. Antipsychotic-induced hyperprolactinaemia occurs overall in up to 70% of patients with schizophrenia, depending on the medications used. It is associated with significant levels of hypogonadism and sexual dysfunction, which in general relates to the degree of prolactin elevation. A consequence of the hypogonadism is clinically significant bone loss which may lead to osteoporosis and increased risk of minimal trauma fracture. Where the potentially offending drug cannot be safely withdrawn to document a normal prolactin, imaging with MRI should be undertaken to exclude a structural pituitary lesion. The management strategy of choice is switching to a prolactin-sparing antipsychotic. Sex steroid replacement can reverse many of the adverse effects including the hypogonadal symptoms and bone loss. Low dose dopamine agonist therapy should be used with caution as a third line treatment, since there have been cases of dopamine agonist-induced exacerbation of psychosis. There is a need for a randomised controlled trial of low dose dopamine agonist therapy versus sex steroid replacement to establish the relative safety and efficacy of each approach.
    Full-text · Article · Jun 2011 · Australian and New Zealand Journal of Psychiatry
Show more