Prognostic significance of serum prolactin levels in advanced breast cancer

Dowsett, Mitch; McGarrick, Gail; Harris, Adrian L.; Coombes, R. Charles; Smith, I. E.; Jeffcoate, S. L.

doi:10.1038/bjc.1983.129

Cited by 44 publications

(19 citation statements)

References 15 publications

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“…In other words, MPA does not prevent a rise in serum PRL levels in rats with progressing tumours. This result is in good agreement with clinical findings which indicate that high serum PRL levels are markers of poor response to endocrine or chemotherapeutic regimens in women with breast cancer (Dowsett et al, 1983;Holtkamp et al, 1984Holtkamp et al, , 1985Pannuti et al, 1985). In particular, Holtkamp et al (1985) have observed that MPA induces a significant increase in serum PRL concentrations in non-responsive patients, while it does not affect this parameter in responsive women.…”

Section: Discussionsupporting

confidence: 86%

High tumour prolactin receptor content and lack of increase in serum prolactin levels as predictors of good response to endocrine therapy in rat mammary cancer

Carlo

Muccioli

Bellussi

et al. 1988

Intl Journal of Cancer

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Correlations between anti-neoplastic activity of medroxyprogesterone acetate (MPA), on the one hand, and serum prolactin (PRL) levels as well as tumour PRL and insulin receptor content, on the other, were investigated in female rats bearing dimethylbenzanthracene (DMBA)-induced mammary tumours. Changes in liver PRL receptor concentrations were also studied. MPA was injected for 15 days. Regression was observed in 16 out of 50 (32%) tumours from rats treated with MPA. Twenty-seven out of 50 (54%) continued to grow regardless of treatment. Stasis was seen in the remaining 7 tumours (14%). Serum PRL levels increased significantly in rats with tumours which were non-responsive to MPA. Concentration of PRL receptors in the liver of all animals was reduced by MPA treatment. A remarkable increase occurred only in those mammary tumours which responded to therapy. The concentrations of PRL receptors in the tumours non-responsive to MPA were similar to those detected in control tumours. Unlike PRL receptors, tumour insulin receptor levels were not modified by MPA treatment. Five out of 14 tumours (35.7%), previously growing in spite of MPA administration, regressed when bromocriptine was added to MPA. A significant reduction in serum PRL levels occurred in all rats undergoing the latter treatment. No difference was observed between responsive and non-responsive animals; on the contrary, the PRL receptor content of responsive tumours increased significantly in comparison with that of non-responsive tumours.

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Section: Discussionsupporting

confidence: 86%

High tumour prolactin receptor content and lack of increase in serum prolactin levels as predictors of good response to endocrine therapy in rat mammary cancer

Carlo

Muccioli

Bellussi

et al. 1988

Intl Journal of Cancer

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“…Moreover, the PRL antagonist G129R was reported to cause apoptosis in breast cancer cells (8, 13). These findings, and the correlation between serum PRL and the incidence and progression of breast tumors (11,12,14), indicate that PRL has a role in human breast cancer. Stromal and adipose tissue are the major sources of estrogen in post-menopausal women, and could exert paracrine control of prolactin and prolactin receptor expression in adjacent mammary epithelial cells.…”

Section: Prolactin (Prl)mentioning

confidence: 95%

A Novel Estradiol/Estrogen Receptor α-dependent Transcriptional Mechanism Controls Expression of the Human Prolactin Receptor

Dong

Tsai‐Morris

Dufau

2006

Journal of Biological Chemistry

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2 -activated transcriptional expression of the hPRLR through PIII. Estradiol produced in breast stroma and adipose tissue, which are major sources of estrogen in post-menopausal women, could up-regulate hPRLR gene expression and stimulate breast tumor growth. Prolactin (PRL),2 a hormone of the lactogen/cytokine family, is produced in the anterior pituitary gland and exerts diverse cellular actions through its transmembrane receptors (PRLR) in several target tissues. Prolactin is a major factor in the proliferation and differentiation of breast epithelium and is the primary hormone in the stimulation and maintenance of lactation. Prolactin is a tumor promoter in rodents (1, 2) and has been implicated in the development of breast cancer. The hPRLR has several forms, including long form (stimulatory) and short form(s) (inhibitory) (3, 4), which are expressed in normal and tumoral breast tissue and in most human breast cancer cells (5-7), and prolactin exhibits synergistic actions with estrogens on the proliferation of these cells (8). There is local production of PRL in mammary epithelial cells, and increased expression of the PRLR long form occurs in a significant number of human mammary tumors (9 -12). A lower ratio of short (inhibitory forms)/long (activating form) receptors reported in breast tumor tissues could cause unopposed prolactin-mediated stimulatory actions of the long form and may contribute to breast tumor development and progression (7). Moreover, the PRL antagonist G129R was reported to cause apoptosis in breast cancer cells (8, 13). These findings, and the correlation between serum PRL and the incidence and progression of breast tumors (11,12,14), indicate that PRL has a role in human breast cancer. Stromal and adipose tissue are the major sources of estrogen in post-menopausal women, and could exert paracrine control of prolactin and prolactin receptor expression in adjacent mammary epithelial cells.Our previous studies on the hPRLR gene revealed its complex 5Ј genomic structure, with multiple (six) alternative non-coding exons 1 and promoter utilization (15,16). These include the preferentially utilized, generic promoter 1/exon-1 (PIII/hE1 3 ), which is also present in rat and mouse, and five human specific exon-1/promoters (hE1 N1-5 ) (15-17). These forms were found to be expressed in breast cancer cells, and variably in other tissues (16). Quantitative competitive reverse transcriptase-PCR analysis showed that E 2 induced increases of PRLR non-coding exon-1 hE1 3 (generic) mRNA transcripts directed by promoter III (hPIII) in breast cancer cells. Also, in transfection studies E 2 activated the hPIII promoter (18). This promoter contains functional Sp1 and C/EBP sites that bind Sp1/Sp3 and C/EBP␤, respectively (16,19). The lack of a formal ERE in the hPIII promoter suggested that the effect of estradiol is mediated through association of the activated ER with relevant DNA binding transfactors. Thus, although there is not a classical ERE within the hPRLR promoter/5Ј-flanking region of hPIII, our ...

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“…Thus, axillary nodal status is correlated with turnout size and hormone receptor status is correlated with tumour nuclear grade [9], pregnancy-specific beta 1-glycoprotein [10], proliferative activity and aneuploidy [11,12], and epidermal growth factor receptors [13]. Other prognostic factors described in the literature include body mass index [14], weight [15], serum prolactin [16], prolactin receptor [17,18], age [19,20], age at first pregnancy [15], and season of turnout detection [7,8,21], but to date the effect of these variables has not been as well defined as nodal and receptor status. In addition, there is a further group of characteristics that appear to influence the risk of developing breast cancer but which have not been studied extensively for their effects on survival.…”

Section: Introductionmentioning

confidence: 99%

Season of tumour detection influences factors predicting survival of patients with breast cancer

Mason

Holdaway

Stewart

et al. 1990

Breast Cancer Res Tr

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The rate of initial detection of breast tumours varies during the year in a seasonal fashion, more tumours being discovered in late spring/early summer than at other times of the year. This phenomenon is particularly pronounced in young women (less than 50 years) with progesterone receptor positive tumours. The present study investigates whether season of tumour detection influences the predictive capacity of several recognised prognostic and risk factors in patients with breast cancer. Axillary nodal status, tumour progesterone receptor status, and season of tumour detection significantly influenced survival in both older (greater than 50 yrs) and younger (less than 50 yrs) patients. Parity, lactational history, body mass index, tumour oestrogen receptor status, and patient age also influenced survival, but these effects were significant only in age groups less than 50 or greater than 50 yrs. Season of detection of tumour did not effect the prognostic significance of axillary nodal status. However, the effect of oestrogen receptor status on survival was more significant in patients who detected their tumours in the spring/summer compared with winter (odds ratio 0.52 and 0.73 respectively). Negative progesterone receptor status was associated with significant poorer survival only in patients with tumours found in the winter. There was a significant survival disadvantage for nulliparous compared with parous women with breast cancer who were greater than or equal to 50 years at diagnosis, and for women who had never lactated compared with those who had lactated, but this disadvantage was restricted to those who found their tumours in the summer. An increased body mass index (greater than or equal to 28) was associated with decreased survival, but this was significant only for those detecting tumours in winter. The increased incidence of detection of breast cancer in spring/summer may reflect cyclic influences on tumour growth. Such influences may be hormonal in nature and may underlie the effect of season of tumour detection on the prognostic influence of lactation, parity, body mass index, and oestrogen and progesterone receptor status in patients with breast cancer.

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Prognostic significance of serum prolactin levels in advanced breast cancer

Cited by 44 publications

References 15 publications

High tumour prolactin receptor content and lack of increase in serum prolactin levels as predictors of good response to endocrine therapy in rat mammary cancer

High tumour prolactin receptor content and lack of increase in serum prolactin levels as predictors of good response to endocrine therapy in rat mammary cancer

A Novel Estradiol/Estrogen Receptor α-dependent Transcriptional Mechanism Controls Expression of the Human Prolactin Receptor

Season of tumour detection influences factors predicting survival of patients with breast cancer

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