Relationship between prolactin, breast cancer risk, and antipsychotics in patients with schizophrenia: a critical review

A recent meta-analysis showed that breast cancer probably is more common in female patients with schizophrenia than in the general population (effect size = 1.25, P < 0.05). Increasing experimental and epidemiological data have alerted researchers to the influence of prolactin (PRL) in mammary carcinogenesis. We therefore investigated the possible relationship between antipsychotic-induced hyperprolactinemia (HPRL) and breast cancer risk in female patients with schizophrenia.A literature search (1950 until January 2015), using the MEDLINE database, was conducted for English-language published clinical trials to identify and synthesize data of the current state of knowledge concerning breast cancer risk (factors) in women with schizophrenia and its (their) relationship between HPRL and antipsychotic medication.Although an increasing body of evidence supports the involvement of PRL in breast carcinogenesis, results of human prospective studies are limited, equivocal, and correlative (with risk ratios ranging from 0.70 to 1.9 for premenopausal women and from 0.76 to 2.03 for postmenopausal women). Moreover, these studies equally do not take into account the local production of PRL in breast epithelium, although amplification or overexpression of the local autocrine/paracrine PRL loop may be a more important mechanism in tumorigenesis. Until now, there is also no conclusive evidence that antipsychotic medication can increase the risk of breast malignancy and mortality.Other breast risk factors than PRL, such as nulliparity, obesity, diabetes mellitus, and unhealthy lifestyle behaviours (alcohol dependence, smoking, low physical activity), probably are of greater relevance in individual breast cancer cases within the population of female patients with schizophrenia.