beta-endorphin and Breast-Neoplasms

Body and mind interact extensively with each other to control health. Emerging evidence suggests that chronic neurobehavioral stress can promote various tumor growth and progression. The biological reaction to stress involves a chemical cascade initiated within the central nervous system and extends to the periphery, encompassing the immune, endocrine, and autonomic systems. Activation of sympathetic nervous system, such as what happens in the "fight or flight" response, downregulates tumor-suppressive genes, inhibits immune function, and promotes tumor growth. On the other hand, an optimistic attitude or psychological intervention helps cancer patients to survive longer via increase in β-endorphin neuronal suppression of stress hormone levels and sympathetic outflows and activation of parasympathetic control of tumor suppressor gene and innate immune cells to destroy and clear tumor cells.

Topics: Animals; beta-Endorphin; Breast Neoplasms; Carcinogenesis; Cell Proliferation; Cytotoxicity, Immunologic; Female; Humans; Immunity, Innate; Mammary Glands, Animal; Mammary Glands, Human; Nerve Tissue Proteins; Neurons; Stress, Physiological; Stress, Psychological; Synaptic Transmission

One case of breast neuroendocrine primary small cell carcinoma with light microscopic and immunohistochemical findings is reported. The patient died of unrelated disease 21 months after diagnosis and treatment by modified radical mastectomy, radiotherapy and subsequent chemotherapy. Immunohistochemical studies revealed cytokeratin and neuroendocrine markers (chromogranin, neuron-specific enolase) immunostaining on tumoral cells. Expression for neuropeptides (met-enkephalin, leu-enkephalin, beta-endorphin) and CALLA antigen was found. Based on this case report and six other previously reported cases, breast neuroendocrine primary small cell carcinoma appears to be a very aggressive tumor for which no firm conclusions regarding treatment can be drawn.

Topics: Aged; beta-Endorphin; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Small Cell; Chromogranins; Cytoplasm; Enkephalin, Leucine; Female; Humans; Immunohistochemistry; Keratins; Mammography; Mastectomy, Modified Radical; Phosphopyruvate Hydratase; Radiotherapy, Adjuvant

From preclimacteric women (n = 10, 45-50 years of age) with gross cystic breast disease, levels of beta-endorphin, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, cortisol and prolactin were assayed radiochemically in the breast cyst fluid and in plasma. The beta-endorphin concentration (fmol/ml) was increased more than fourfold in the breast cyst fluid (17.6 +/- 4.6 SEM) than in plasma (4.2 +/- 0.5 SEM). In the breast cyst fluid, estradiol was increased 41-fold (1738.2 +/- 350.5 SEM pg/ml), and progesterone 47-fold (65.47 +/- 8.25 SEM ng/ml) more than in plasma. The significantly increased values of beta-endorphin, estradiol and progesterone in the breast cyst fluid and the identification of beta-endorphin in cyst-lining epithelia demonstrate the local synthesis. Growth factor-like properties of beta-endorphin and estradiol are accountable for the propagation of cystic changes. The autonomic formation and function of beta-endorphin, estradiol and progesterone in cyst compartments can not be related with the levels of luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone and cortisol, which were significantly higher in plasma than in the breast cyst fluid. In the breast cyst fluid, prolactin could not detected to be significantly higher than in plasma. In addition the plasma-concentration of testosterone, androstenedione, thyroxin, triiodothyronine, thyroid-binding globulin, sexual-hormone-binding-globulin could be detected within the normal range. In this study we could demonstrate the synergism of beta-endorphin, steroid hormones and peptide hormones which advance the growth of gross cystic disease of preclimacteric women. Beta-endorphin was also examined by immunocytochemical assays (fluorescence, alkaline phosphatase and horseradish peroxidase method), in 11 women with pure fibrocystic disease, in 7 women with fibrocystic disease combined with a carcinoma in situ and in 15 women with fibrocystic disease combined with invasive carcinoma of the breast. Sections of frozen and paraffin embedded tissue of the same patient were reacted with anti-beta-endorphin antiserum. The immunoreactivity of beta-endorphin was intense in normal, proliferative altered and cyst-lining epithelia of fibrocystic disease and decreased in atypical epithelia and carcinoma cells of the breast. The degree of beta-endorphin staining is related to the degree of cell differentiation. In addition, nuclea

Topics: beta-Endorphin; Breast; Breast Neoplasms; Female; Fibrocystic Breast Disease; Hormones; Humans; Immunohistochemistry; Middle Aged; Receptors, Cell Surface; Steroids

Up to 50 % of women receiving aromatase inhibitor (AI) complain of AI-associated musculoskeletal symptoms (AIMSS) and 15 % discontinue treatment. We conducted a randomized, sham-controlled trial to evaluate whether acupuncture improves AIMSS and to explore potential mechanisms. Postmenopausal women with early stage breast cancer, experiencing AIMSS were randomized to eight weekly real or sham acupuncture sessions. We evaluated changes in the Health Assessment Questionnaire Disability Index (HAQ-DI) and pain visual analog scale (VAS) following the intervention compared to baseline. Serum estradiol, β-endorphin, and proinflammatory cytokine concentrations were measured pre and post-intervention. We enrolled 51 women of whom 47 were evaluable, including 23 randomized to real and 24 to sham acupuncture. Baseline characteristics were balanced between groups with the exception of a higher HAQ-DI score in the real acupuncture group (p = 0.047). We did not observe a statistically significant difference in reduction of HAQ-DI (p = 0.30) or VAS (p = 0.31) between the two groups. Following eight weekly treatments, we observed a statistically significant reduction of IL-17 (p ≤ 0.009) in both groups. No significant modulation was seen in estradiol, β-endorphin, or other proinflammatory cytokine concentrations in either group. We did not observe a significant difference in AIMSS changes between real and sham acupuncture. As sham acupuncture used in this study may not be equivalent to placebo, further studies with a non-acupuncture arm may be required to establish whether acupuncture is beneficial for the treatment of AIMSS.

Topics: Acupuncture Therapy; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; beta-Endorphin; Breast Neoplasms; Female; Humans; Inflammation Mediators; Middle Aged; Musculoskeletal Pain; Time Factors; Treatment Outcome

Two or three decades ago, cancer pain was treated by surgical/chemical hypophysectomy. In one report, the control of central pain (thalamic pain syndrome) was also approached with chemical hypophysectomy. Although in most of the patients these treatments resulted in a decrease in severe pain, concomitantly severe adverse effects (panhypopituitarism, diabetes insipidus and visual dysfunction) occurred in most patients. This historical evidence prompted us to perform Gamma Knife surgery (GKS) for this kind of intractable severe pain using a high irradiation dose to the pituitary stalk/gland. In the majority of patients, marked pain relief was achieved, surprisingly without any of the complications mentioned above.. A prospective multicenter study was conducted to evaluate the efficacy and safety in patients treated in Prague, Hong Kong and Tokyo. Indications of this treatment were: (1) failure of other effective treatment approaches prior to GKS, (2) good general patient condition (Karnofsky performance status >40%), (3) response to morphine for pain control (cancer pain), and (4) no previous radiotherapy of brain metastases (GKS/conventional radiotherapy). Eight patients with severe cancer pain due to bone metastasis and 12 patients with post-stroke thalamic pain syndrome were treated with GKS. The target was the border between the pituitary stalk and gland. Maximum dose was 160 Gy for cancer pain and 140 Gy for central pain. Follow-up included 6 patients (>1 month) with cancer pain and 8 patients (> 6 months) with thalamic pain syndrome.. All patients (6/6) with cancer pain experienced significant pain reduction, and 87.5% (7/8) of the patients with thalamic pain had initially significant pain reduction. In some patients, pain reduction was delayed for several hours. Pain relief was noted within 7 days (median 2 days). No recurrence was observed in the patients with cancer pain. However, in 71.4% (5/7) of the patients with thalamic pain syndrome, disease recurred during the 6-month follow-up. Up to now, other complications have not been observed.. Our clinical study protocol is only preliminary. Further clinical results on the management of thalamic pain are required to develop this treatment protocol. However, efficacy and safety have been shown in all our cases. In our opinion, this treatment has a potential to control severe pain, and GKS will play an important role in the management of intractable pain.

Topics: beta-Endorphin; Bone Neoplasms; Breast Neoplasms; Female; Humans; Hypophysectomy; Male; Pain; Pituitary Gland; Prospective Studies; Prostatic Neoplasms; Radiosurgery; Thalamus; Treatment Outcome

We examined the association between endogenous opioid β-endorphin, cancer progression and pain in a transgenic mouse model of breast cancer, with a rat C3(1) simian virus 40 large tumor antigen fusion gene (C3TAg). C3TAg mice develop ductal epithelial atypia at 8 weeks, progression to intra-epithelial neoplasia at 12 weeks, and invasive carcinoma with palpable tumors at 16 weeks. Consistent with invasive carcinoma at 4 months of age, C3TAg mice demonstrate a significant increase in hyperalgesia compared to younger C3TAg or control FVBN mice without tumors. Our data show that the growing tumor contributes to circulating β-endorphin. As an endogenous ligand of mu opioid receptor, β-endorphin has analgesic activity. Paradoxically, we observed an increase in pain in transgenic breast cancer mice with significantly high circulating and tumor-associated β-endorphin. Increased circulating β-endorphin correlates with increasing tumor burden. β-endorphin induced the activation of mitogenic and survival-promoting signaling pathways, MAPK/ERK 1/2, STAT3 and Akt, observed by us in human MDA-MB-231 cells suggesting a role for β-endorphin in breast cancer progression and associated pain.

Topics: Animals; beta-Endorphin; Biomarkers; Breast Neoplasms; Cancer Pain; Cell Line, Tumor; Disease Progression; Female; Humans; Mice; Mice, Transgenic

Breast cancer survival has improved motivating the need for better understanding of the sequelae of the disease and its treatments. Lab studies suggest opioids modify cancer cell growth but the association of opioids with cancer progression in humans is not clear. This review aims to summarize recent findings related to opioid use and breast cancer progression.. Opioid-sparing analgesia may be associated with better survival in cancer patients. In-vitro research suggests that treatment with μ-opioid receptor antagonists inhibits cancer proliferation, and shows some promise for attenuating tumor growth in humans, thereby enhancing survival. Prescription use of opioids does not appear to influence the risk of recurrence in patients, though the evidence comes from a single large registry-based observational study. Ongoing clinical trials are comparing opioid-sparing regional anesthesia with general anesthesia for the risk of breast cancer recurrence.. The association of opioids with breast cancer progression is controversial. Further observational studies are needed. There is currently no clear evidence to suggest that opioid use should be avoided in breast cancer patients because of concerns regarding the risk of breast cancer recurrence.

Topics: Analgesics, Opioid; Anesthesia; beta-Endorphin; Breast Neoplasms; Cell Line, Tumor; Clinical Trials as Topic; Disease Progression; Dose-Response Relationship, Drug; Humans; Immunity, Cellular; Neoplasm Recurrence, Local; Neovascularization, Pathologic; Polymorphism, Genetic; Prognosis; Receptors, Estrogen; Receptors, Opioid, mu

Neither the measured stress-hormones, nor Beta-Endorphin have been influenced by music therapy. Music therapy should be initiated before the beginning of chemotherapy, preferably shortly after the operation. The greatest profit of an accompanying music therapy is between the chemotherapy courses, because the whole energy of the patient during chemotherapy is directed to questions, worries and practical aspects.

Topics: Adrenocorticotropic Hormone; Adult; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; beta-Endorphin; Breast Neoplasms; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Dehydroepiandrosterone; Female; Fluorouracil; Humans; Hydrocortisone; Immunoradiometric Assay; Luminescent Measurements; Methotrexate; Music Therapy; Postoperative Care; Radioimmunoassay; Random Allocation; Time Factors

Topics: Adenofibroma; beta-Endorphin; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Female; Humans

Histochemical and immunohistochemical methods were used to examine 29 malignant tumors (18 lobular and 11 invasive carcinomas) and 34 fibroadenomas of the mammary gland (MG). APUD cells containing serotonin, melatonin, and beta-endorphine were shown to be present in the duct epithelium of the normal MG and its pericanalicular fibroadenoma. APUD cells were detected in 21 of the 29 malignant tumours of MG. Hormonal differences of APUD cells were found in poorly and well differentiated carcinomas: the former contained serotonin, melatonin, and beta-endorphine (inhibitors of proliferation), the latter--insulin and adrenocorticotropic hormone (stimulators of cell division). Such differences in the endocrine function of MG malignant tumors are likely to be significant in the clinical course and determination of prognosis for carcinomas of various differentiation.

Topics: Adenofibroma; Adrenocorticotropic Hormone; APUD Cells; beta-Endorphin; Breast Neoplasms; Carcinoma; Fibrocystic Breast Disease; Humans; Immunohistochemistry; Melatonin; Serotonin

Recent studies showed that both the pineal gland and the endogenous opioid system are involved in the modulation of the immune system and in the regulation of tumor growth. Moreover, a relationship between pineal and opioid system has been demonstrated. In order get an overall view of the psychoneuroendocrine interactions in cancer patients, the levels of melatonin, the most important pineal hormone, and of beta-endorphin have been measured on blood samples collected during the morning. The study was carried out on 54 patients, 42 healthy subjects, and in 34 patients having illnesses other than cancer. Breast cancer, lung carcinoma, and colorectum cancer were the three neoplasms detected in the patients investigated. Growth hormone (GH), somatomedin-C and prolactin (PRL) levels were also determined. beta-endorphin levels were found to be substantially within the normal range in patients with cancer, whereas those of melatonin were raised in several cases. The beta-endorphin/melatonin ratio was higher than 2 in normal subjects, in non-neoplastic patients and in most cancer patients without metastases, whereas this ratio was lower than 2 in almost all patients in a metastatic stage of the disease. Neither melatonin levels nor those of beta-endorphin appeared to be significantly correlated with GH, somatomedin-C, and PRL concentrations. The low beta-endorphin/melatonin ratio observed in metastatic patients suggests the presence of an unbalanced relation between the pineal and the opioid system in those subjects. Therefore, an anomalous relationship between pineal function and opioid activity might play a role in the clinical course of neoplastic disease.

Topics: Adult; beta-Endorphin; Breast Neoplasms; Colonic Neoplasms; Endorphins; Female; Growth Hormone; Humans; Insulin-Like Growth Factor I; Lung Neoplasms; Male; Melatonin; Middle Aged; Neoplasms; Pineal Gland; Prolactin; Rectal Neoplasms

Endogenous opioid peptides have been seen to play a role in regulating immunity and tumor growth. This study was carried out to investigate opioid activity in human cancer. We evaluated by radioimmunoassay beta-endorphin plasma levels on blood samples collected at 9.00 a.m. from 121 cancer patients and 42 healthy subjects. In 22 cancer patients and in 12 controls, beta-endorphin circadian rhythm was also investigated. Finally, in 14 cancer patients and in 10 controls GH, PRL, FSH, LH and cortisol serum levels were measured after the administration of a metenkephalin analogue, FK 33-824 (0.3 mg i.v.). No significant differences were seen in beta-endorphin mean levels between cancer patients and normal subjects. Moreover, no differences were found between patients with or without metastases, nor between those with or without chronic pain. beta-Endorphin circadian rhythm appeared to be altered in 16/22 cancer patients, and anomalous hormonal responses to FK 33-824 were seen in 13/14 patients. This study shows an altered opioid activity in human neoplasms, whose clinical significance remains to be determined.

Topics: Adult; Aged; beta-Endorphin; Breast Neoplasms; Circadian Rhythm; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Female; Gastrointestinal Neoplasms; Humans; Hydrocortisone; Lung Neoplasms; Male; Middle Aged; Pituitary Hormones, Anterior; Radioimmunoassay