Possible influence of prolactin secretion on the survival time in untreatable metastatic triple negative breast cancer patients

Abstract

It is known since more than 30 years that the pituitary hormone prolactin (PRL) may stimulate breast cancer development and growth in experimental conditions.1 In contrast, despite the fact that PRL is one of the first identified endogenous factor involved in the stimulation of mammary tumors, as well as despite the evidence that cancerrelated hyper-prolactinemia has been proven to be associated with a poor prognosis,2‒4 very few clinical studies have been performed in an attempt to investigate the possible prognostic significance of PRL secretion in human breast cancer and the influence of the inhibition of PRL secretion on the clinical course of breast tumors, and in particular no clinical study of PRL secretion in breast cancer has been carried during the last 20 years. This evidence would be the consequence of the fact that almost all oncological studies performed in the last 20 years have been substantially limited to the investigation of the only biological and genetic characteristics of the different breast cancer sub-types rather than to concomitantly evaluate the biological response of patients, including their endocrinological and immune status, even though preliminary clinical studies had already suggested that the association of anti-prolactinemic agents, such as bromocriptine and cabergoline, may improve the efficacy of the commonly used oncological therapies for the metastatic breast cancer.5 In any case, it has to be remarked that the relation between PRL and human breast cancer is very complex, and controversial results have been reported in the literature, particularly in the biologically more aggressive triple negative breast cancer (TNBC), which represents about 20% of human mammary tumors, since either a stimulatory6 or an inhibitory effect7 has been reported. TNBC is defined as a breast tumor lacking the expression of ER, PgR and epidermal growth factor-2 (HER2). Particularly controversial are the results concerning the physiopathological and prognostic significance of the expression of PRL-receptor (PRL-R) in breastcancer. In mammary carcinomas other than TNBC, PRL-R expression is generally associated with a less malignancy and a better prognosis,8 whereas its significance in TNBC has still to be better defined, even though preliminary results would suggest that the evidence of PRL-R expression would prevent the onset of TNBC and would be associated with a more favourable prognosis.7 In any case, the detection of PRL-R expression could allow a novel sub-classifier of TNBC, consisting of TNBC with positivity for PRL-R expression and TNBC without PRL-R expression, which could constitute quadruple negative breast cancer (QNBC) sub-type, being negative also for PRL-R. Preliminary studies would show that PRL-R expressionis down regulated in TNBC.7 PRL antagonists have been proven to inhibit breast cancer cell proliferation by inducing the apoptosis,9 whereas no efficacyhas been referred with PRL-R antagonists.7 Because of the controversial results about the effects of PRL on TNBC growth in vitro and in experimental conditions,6,8 further informations may be achieved by investigating PRL secretion in TNBC patients, by correlating its behavior with the clinical course of disease. This preliminary study was performed to evaluate PRL bloodlevels in untreatable metastatic TNBC patients, for whom no other standard anticancer therapies were available, then suitable for the only palliative therapy, in an attempt to identify possible differences in the survival time in relation to PRL blood concentrations.