Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recent findings regarding the possible relation of prolactin to human breast cancer are reviewed. Prolactin is a single-chain polypeptide hormone secreted by the anterior pituitary; it appears important to the development and growth of mammary tumors in mice and rats. Certain drugs (L-dopa, the ergot derivatives) inhibit the release of prolactin from the anterior pituitary and lower its serum concentration. Chlorpromazine and other phenothiazines block the synthesis, release, or action of prolactin-inhibiting factors leading to increased prolactin secretion. The midcycle serum estrogen elevation does not increase serum prolactin but often high doses of estrogen will. Mammary tumors in mice and rats appear different from those in human, being of alveolar origin while human tumors are thought to be ductal. Also, rodent cancers do not usually metastasize, even when large. About 40% of human breast cancers respond to endocrine therapy while in Sprague-Dawley rats induced mammary tumors are 80% hormone responsive. In mice hyperplastic nodules but not mammary cancers respond to horomone deprivation. Prolactin is a key hormone in the stimulation of hyperplastic nodules in mice and mammary tumors in rats. The effects of progesterone on these growths is not clear. Serum prolactin levels normally vary throughout the day. Levels are not different in cancer patients but certain families with high cancer rates have been shown to have higher than normal serum levels. Although prolactin receptors have been identified in mouse and rat mammary tissue and tumors and prolactin responsiveness of the tumors correlated with the number of such receptors, these receptors have not been identified in human breast cancer cells. Patients have responded to L-dopa with relief of bone pain and a 50% decrease in serum prolactin. Suppressing atypical precancerous lesions by depriving them of their hormonal support offers the best chance for preventing eventual development of breast cancer. In vitro determination of the presence of prolactin receptors in human breast tumor tissue may allow accurate prediction of response to endocrine ablation. Variations in prolactin receptors may account for response differences of breast tumors to different doses of estrogen. Near-zero prolactin levels following hypophysectomy in some patients have been correlated with clinical remissions. Combinations of drugs to reduce serum prolactin levels or antagonize the hormones's effect on the breast may be needed to obtain results.
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PMID:Prolactin and breast carcinoma. 108 86

Pretreatment plasma concentrations of total testosterone, prolactin, and total estradiol-17 beta (E2) were measured in 123 prostatic cancer patients who were categorized into groups according to the UICC classification. Patients with intracapsular tumour without metastases had significantly higher (p less than 0.05) pretreatment total estradiol levels than those with more advanced disease. The patients were treated either by orchiectomy or estrogens. The mean follow-up time was 48 months. Higher pretreatment estradiol and testosterone levels were associated with better survival. Prolactin assays seemed to be of no value in this respect.
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PMID:Pretreatment hormone levels in prostatic cancer. 318 1

Prolactin secreting tumors account for ten to twenty percent of all intracranial lesions. The patients harboring these tumors present with amenorrhea, galactorrhea, other ovulatory disorders, infertility, delays in puberty and mixed polyendocrinopathy. These tumors are diagnosed by the measurement of serum prolactin levels, Goldmann-Bowl perimetry, and either computed axial tomography or magnetic resonance imaging. Protein secreting tumors are usually benign lesions and historically have been treated by partial or total hypophysectomy or radiation therapy. Surgical resection of the lesion often is followed by recurrence and administration of proton beam radiation therapy results in the development of a panhypopituitary state. Growth of pituitary tumors is controlled with the administration of dopamine agonists such as bromocriptine and prospective studies have suggested that these drugs are now the preferred method of treatment for primary lesions and recurrences.
Cancer Metastasis Rev 1986
PMID:Diagnosis and management of prolactinomas. 354 32

Hypophysectomy was studied for its possible effects on cancer by alt eration of the endorcines at the New York Hospital-Cornell Medical Center beginning in 1953. The major effort has been the treatment of 850 cases of metastic breast cancer. In 80 patients with other types of metastatic cancer benefit was found only in 50 cases of prostatic cancer. Prolactin is mediated directly from the anterior pituitary to breast tissue where it aids and abets the growth of breast cancer; its secretion is largely dependent on the estrogen produced in ovaries and adrenals. In humans estrogen given after total hypophysectomy is found to be ineffective in altering metastases. Growth hormone is also produced in the anteriod lobe of the pituitary but its production is not dependent on an estrogen feed-back mechanism. If the primary cancer is dependent on the presence of prolactin, failures with hypophysectomy are explained the tumor having gained autonomy and being no longer so dependent. Contraindications to hypophysectomy include extensive pulmonary, liver, or brain metastases and any systemic disease that would preclude major surgery. Following a remission after oophorectomy, another remission with hypophysectomy may often be obtained. Neither the pathological type of a breast cancer nor the location of metastases alter the results. However the longer the interval between mastectomy and reactivation of the tumor, the more favorable the outlook. Maintenance substitution therapy following removal of the pituitary employs daily hydrocortisone, 17.5 mg orally, or equivalent steroid preparations. The mortality rate is 2% in the first 30 days after operation. In 88 patients evaluated 2 years after operation those who had received a remisssion lasting over 6 months survived nearly 5 times longer than those unbenefitted by the operation. The intracranial procedure is preferred. In cases of failure or when a remission terminates, male hormone therapy, chemotherapy, or radiation may have limited value.
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PMID:Hypophysectomy for metastatic cancer. 466 60

Biopsy specimens of 55 human mammary carcinomas (38 primary and 17 metastatic) were assayed for prolactin receptors (PrlR). Prolactin bound specifically to 32 (58%) of the tumor biopsy specimens. The apparent Kd for PrlR in individual tumors ranged from 15 pM to 2.3 nM (mean 600 pM, n = 5) and the concentration of PrlR ranged from 0 to 44.5 fmoles/mg protein. Estrogen receptors (ERP) were also detected in 28 of the 32 tumors which had PrlR. Overall, there was no correlation between PrlR and ERP. However, the mean concentration of PrlR was significantly higher (p less than 0.01) in tumors with 6-100 fmoles/mg protein ERP (approximately 13 fmoles PrlR) than in tumors with either less than 6 or greater than 250 fmoles ERP (4.0 +/- 0.4 and 6.5 +/- 1.8 respectively fmoles PrlR). Analysis of PrlR concentration as a function of patient age also showed no overall correlation, but the mean PrlR in tumors from women aged 60-70 was significantly higher (p less than 0.01) than in those from either younger or older women. A higher concentration of PrlR was observed in tumors which were classified histologically as medium or well differentiated (6.1 +/- 1.2 and 11.1 +/- 2.1, respectively) than in those classified as poorly differentiated (3.3 +/- 1.2) (p less than 0.03). There was a negative correlation between PrlR concentration and membrane yield from the tumors (r = 0.43, p less than 0.02). The membrane yield correlated with the ratio of tumor cells to stroma (histologically) (r = 0.63, p less than 0.001). In tumors from 12 patients with metastatic disease on whom follow up after endocrine-related therapy was available, the mean PrlR concentration was significantly higher in the non-responding group (8.2 +/- 3.0) than in the responding group (3.4 +/- 4.2, p = 0.05).
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PMID:Prolactin binding by human mammary carcinoma: relationship to estrogen receptor protein concentration and patient age. 629 28

Serum levels of chorionic gonadotropin (HCG), testosterone, luteinizing hormone (LH) and prolactin were evaluated with the radioimmunoassay in 59 patients with lung cancer, 10 patients with benign lung disease, and 37 normal controls. HCG was present in 6.8% of the lung cancer patients but in none of the subjects of the other two groups. Prolactin and LH levels were significantly higher than normal in lung cancer patients (respectively p less than 0.001 and p less than 0.01) as well as in patients with benign lung disease (p less than 0.01 for both the hormones). Testosterone levels were significantly lower than normal in patients with lung cancer (p less than 0.05) but not in those with benign lung disease. When the patients were analyzed according to histologic type and clinical stage of disease, significantly lower than normal values of testosterone were found in patients with small cell carcinoma or squamous cell carcinoma. In the squamous cell carcinoma group, the patients with lymph node metastases had significantly lower testosterone levels than those without lymph node metastases. From these results, we may hypothesize that the raised levels of prolactin and LH are related to a pulmonary pathology, not necessarily neoplastic, whereas the low levels of testosterone are related to the presence of the tumor.
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PMID:Abnormal serum hormone levels in lung cancer. 631 49

In a long-term follow-up study, prolactin levels were measured in 149 patients with advanced metastatic breast cancer. Control groups included 221 patients with primary operable breast cancer and 150 women with benign breast disease. Hyperprolactinemia (greater than 1,000 mIU/I; HYPRL) occurs in 44% of patients with metastatic breast cancer in the course of the disease (p less than 0.001 compared to patients with non-metastatic disease). HYPRL is associated with progressive breast cancer in 88% of cases. In patients experiencing several episodes of disease remission and relapse, incidence of HYPRL increases with each relapse. Prolactin blood levels return to normal if hyperprolactinemic patients experience remission after chemotherapy. Patients expressing HYPRL have a shorter survival time after mastectomy when compared to patients who never developed HYPRL (154/89 months, p = 0.01). It is concluded that HYPRL is of prognostic significance and a reliable indicator of progressive disease in advanced metastatic breast cancer.
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PMID:Hyperprolactinemia is an indicator of progressive disease and poor prognosis in advanced breast cancer. 648 Jan 53

The authors study the correlation existing between prolactin and E-17-beta in breast cancer. In both premenopausal and post-menopausal patients prolactin may be useful as an evolutive marker. Prolactin increases particularly as a consequence of the metastatic growth. E-17-beta shows no variation when studied during the luteal phase, diminishes after the extirpation of the primitive tumor, and augments again with metastases development. After chemotherapy the amount of E-17-beta becomes almost undetectable. No correlation was found between prolactin and E-17-beta; apparently, the prolactin increase does not depend directly from the amount of circulating estradiol, but relies on the activity of the hypothalamic-hypophyseal system. With regard to E-17-beta, this product also augments after ovariectomy, suggesting an ectopic production starting on adrenal gland precursors, perhaps modulated by prolactin.
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PMID:[Correlations between PRL and 17-beta-E in human breast cancer]. 654 90

A patient with a macroprolactinoma and extrasellar extension was treated by incomplete transfrontal surgery, external irradiation and additional bromocriptine (Br) treatment. After 4 years, partial bromocriptine resistance developed (a rare occurrence) together with the appearance of intracranial metastases. 123I-Iodobenzamide was helpful in evaluating the dopamine D2 receptor status of the metastatic tumour both in vivo using single-photon emission computed tomography (SPECT) and in vitro. Prolactin release by the cultured metastatic tumour cells was more potently inhibited by CV 205-502 than by bromocriptine. The patient, treated by surgery, irradiation and CV 205-502, developed a ptosis of the left eye and a transient psychiatric delusional state, the latter probably an effect of the dopamine agonist. As the right frontal metastasis was markedly positive on SPECT with 111In-SMS, somatostatin treatment was added to the CV 205-502.
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PMID:Intracranial dissemination of a macroprolactinoma. 810 Nov 48

Two cases of breast carcinoma associated with prolactinoma are presented. Literature review reveals only five previous case reports of this association. Both of our cases occurred in women, aged 55 and 34. Both were typical of the reported cases in that they had long histories of amenorrhea before diagnosis of prolactinomas and breast carcinomas. One patient had a three and a half year history of atypical ductal hyperplasia and a prominent intraduct component in the invasive tumor. Both had axillary lymph node metastases. The significance of the association of breast carcinoma with prolactinoma is discussed. Whereas studies in animals have shown prolactin to be an initiator and promoter of breast carcinoma, studies in humans have been inconclusive. Some studies have shown raised levels of prolactin in patients with breast carcinoma and their daughters, while others have not. The paucity of case reports linking breast carcinoma and prolactinoma may indicate that the association is mere coincidence, but studies evaluating the relationship between breast carcinoma and all forms of hyperprolactinemia need to be conducted before a causal link is dismissed. Prolactin may act as a cofactor with, for example, estrogen or stress, to induce breast carcinoma.
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PMID:Two case reports of breast carcinoma associated with prolactinoma. 927 Oct 27


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