Thyroid Hormones & Breast Cancer

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Thyroid Hormones & Breast Cancer

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Aldinger KA, Schultz PN, Blumenschein GR, Samaan NA - "Thyroid-stimulating hormone and prolactin levels in breast cancer" Arch Intern Med 138(11):1638-41 (1978)

Serum thyroid-stimulating hormone (TSH) and prolactin (PRL) levels were measured before and after intravenous administration of protirelin to 148 patients with breast carcinoma. There was a high prevalence (36%) of elevated basal TSH; however, most of the patients were euthyroid and had normal serum thyroxine and T3 resin uptake. The PRL level was elevated in 22% of the cases. Both the mean PRL and the mean TSH levels for the breast cancer patients were significantly elevated above the respective means in a control group. We could find no correlation between serum TSH and PRL levels, suggesting that the purported association between a decreased thyroid state and breast cancer is probably not mediated through an increased PRL level. The mean survival and mean disease-free interval were shorter for patients with either elevated TSH or elevated PRL levels, but in neither case was the difference statistically significant.

Angeli A, Dogliotti L, Agrimonti F, Faggiuolo R, Cavallo R, Tibo A - "Thyroid hormone levels in human breast cyst fluid" Acta Endocrinol (Copenh) 107(2):230-6 (1984)

Radioimmunoassayable levels of total and free 3,5,3'-triodothyronine (T3) and thyroxine (T4), thyroid stimulating hormone (TSH), thyroxine binding globulin (TBG) and prolactin (Prl) were measured in a series of samples of breast cyst fluid (BCF) aspirated from 73 pre-menopausal women with gross cystic disease of the breast and in coincidental blood samples. In BCF free T3 and free T4 were consistently higher than in plasma (P less than 0.001) as was also total T3 in the majority of cases (P less than 0.05). Total T4, TBG and Prl were much lower than in plasma (P less than 0.001). TSH was roughly as in plasma. No correlation was found between plasma and BCF values. The results indicate that thyroid hormones may be accumulated in their effective form in the cyst fluid. A highly significant inverse correlation was found between intracystic free T3 and log (Prl). Our data, considered in relation to previous experimental evidence, suggest the possibility that thyroid hormones act at the breast level in concert with Prl. Accumulation of thyroid hormones in BCF could play a role in the development or maintenance of gross cystic disease of the breast or be a mere consequence of the cystic changes.

Bartsch C, Bartsch H, Fuchs U, Lippert TH, Bellmann O, Gupta D - "Stage-dependent depression of melatonin in patients with primary breast cancer. Correlation with prolactin, thyroid stimulating hormone, and steroid receptors" Cancer 64(2):426-33 (1989)

Serum melatonin was determined over 24 hours in 35 patients with breast cancer with either a fresh primary tumor (n = 23) or a secondary tumor (n = 12) and in 28 patients with untreated benign breast disease (controls) having a fibroadenoma (n = 10), fibrocystic mastopathy (n = 14), or other breast diseases (n = 4). Circadian rhythms existed in all groups with acrophases at 2 a.m. A 50% depression of peak and amplitude occurred in the group of patients with primary breast cancer compared
with age-matched controls (P less than 0.001, P less than 0.01). The peak declined with increasing tumor size: 27% at Stage T1, 53% at T2 (P less than 0.001), and 73% at T3 (P less than 0.05). In contrast, patients with secondary breast cancer, particularly those receiving antiestrogen therapy, had a melatonin peak similar to controls. These results demonstrated a transient depression of pineal melatonin secretion in primary breast cancer and indicated a dynamic role of the pineal gland in
malignancy. To investigate some endocrine effects of a depressed melatonin peak, the 24-hour rhythms of prolactin (PRL) and thyroid stimulating hormone (TSH) were determined in patients with primary breast cancer and compared with patients with secondary breast cancer. The PRL had significant circadian rhythms in both groups; but acrophases occurred at midnight in patients with secondary breast cancer, and there were unusually high concentrations at noon in patients with primary breast
cancer. Circadian rhythms were not seen for TSH, but the 24-hour average secretion was depressed by 45% (P less than 0.01) in patients with primary breast cancer. The abnormal concentrations of PRL and TSH in these patients could be due to a depressed melatonin peak normally serving as a central circadian synchronizer and modulator of the secretion of adenohypophysial hormones. Additionally, a positive correlation existed between the nocturnal melatonin peak and progesterone and androgen receptor concentrations in primary tumors indicating a direct involvement of melatonin in the growth control of breast cancer.

Cupceancu B, Pop A, Purice M, Mogo? I - "Serum and intracystic levels of thyroxine (T4) and triiodothyronine (T3) in women with breast macrocysts" Endocrinologie 25(4):209-15 (1987)

In 15 patients with a total of 22 breast macrocysts serum and intracystic T4 and T3 and intracysts TSH were concomitantly radioimmunoassayed (using a technique with polyethylene glycol (PEG) for T3, T4, and a double antibody technique for TSH). While in most cysts (17/22) the T4 values were under those in the serum, in 21 cysts T3 was 2-18 times above the serum values. Intracystic TSH was at the lower limit of the normal serum TSH values whereas prolactin (PRL) and thyroglobulin (TGL) assayed in several cysts were not different from their serum value. It suggests that breast macrocysts are able to concentrate or even produce triiodothyronine.

Deshpande N, Mitchell I - "Further observations on the hormonal regulation of alpha-glycerolphosphate dehydrogenase in rat mammary gland: a possible role for prolactin and thyrotropin" Horm Metab Res 13(10):572-4 (1981)

The roles of prolactin and thyrotropin (TSH) in the regulation of alpha-glycerolphosphate dehydrogenase (alpha-GPDH) activity in rat mammary gland were investigated by the administration of thyroid releasing hormone, bromocriptine, prolactin, TSH and triiodothyronine (T3). TRH administration failed to induce alterations in the glands from intact animals but stimulated the activity in castrated and adrenalectomized animals. Bromocriptine administration was without any effect in either group of animals. Administration of ovine prolactin to hypophysectomized rats did not affect the activity, on the other hand, treatment with either TSH or T3 resulted in a highly significant increase in the activity. Combined administration of prolactin and TSH to hypophysectomized animals showed that prolactin is capable of partially inhibiting the TSH-induced increase. It is suggested that glucocorticoids exert primary control over the enzyme's activity with the pituitary
hormones only playing a permissive role in its regulation.

García-Solís P, Aceves C - "5'Deiodinase in two breast cancer cell lines: effect of triiodothyronine, isoproterenol and retinoids" Mol Cell Endocrinol 201(1-2):25-31 (2003)

Thyroid hormones participate in the regulation of growth, development and energy expenditure of vertebrates. Type I (D1) and type II 5'deiodinases catalyze the peripheral conversion of the thyroid prohormone thyroxine to the active form triiodothyronine (T3). D1 is expressed in organs like liver, thyroid, and lactating mammary gland. This enzyme is regulated in an organ-specific manner by a wide number of factors like carbohydrates, T3, thyrotropin, and catecholamines. However, it has been shown that in several types of cancer the expression of D1 is reduced, lost, or regulated by different components. In the present work we describe the expression and regulation of 5'deiodinases in two breast cancer cell lines: MCF-7 (ovarian hormone-dependent) and MDA-MB-231 (ovarian hormone-independent). Our results showed that MCF-7 cells expressed D1 activity ( approximately 10 pmol I(-)/mg protein per h), which was stimulated only by retinoic acid treatments, but not by T3 or the beta-adrenergic agonist isoproterenol. In MDA-MB-231 cells, deiodinase activity was not detected in control conditions nor under any of these treatments. These results support the notion that D1 expression could represent a sensitive differentiation marker.

González-Sancho JM, Alvarez-Dolado M, Caelles C, Muñoz A - "Inhibition of tenascin-C expression in mammary epithelial cells by thyroid hormone" Mol Carcinog 24(2):99-107 (1999)

Multiple data suggest a relationship between thyroid hormone (triiodothyronine (T3)) and carcinogenesis. Studies on breast cancer have been inconclusive, suggesting contradictory effects of thyroid status and diseases. Recently, we reported that expression of the extracellular matrix glycoprotein tenascin-C is modulated by T3 during rat brain development. Because tenascin-C has been reported to have growth-, motility-, and angiogenic-promoting activities and to become upregulated during tumorigenesis in breast carcinoma and stromal cells, we analyzed the effects of T3 on tenascin-C expression in mammary epithelial cells. In this study, we showed that tenascin-C RNA expression was inhibited by T3 in normal un-transformed EpH4 mouse mammary epithelial cells expressing appropriate receptors. T3's action appeared to be due to a decreased half-life of the tenascin-C mRNA, with a maximum effect (85% at 100 nM) 48 h after addition. T3 also downregulated tenascin-C in the human mammary tumor cell line SKBR-3, which expresses endogenous thyroid receptors. Immunoprecipitation experiments confirmed that tenascin-C protein content was also decreased by T3 in EpH4 cells (70% reduction at 100 nM). Dexamethasone had a similar inhibitory effect (70% at 100 nM), whereas estradiol, the antiestrogen ICI 164,384, progesterone, and all-trans retinoic acid did not alter tenascin-C expression. Our data demonstrate an inhibitory action of T3 on tenascin-C expression in mammary epithelial cells that may play a role in the physiological regulation of this gene and in neoplastic processes.

Greenblatt RB, Mahesh VB, Sullivan D - "Gross cystic disease of the breast" Maturitas 9(2):171-81 (1987)

The aetiology of fibrocystic disease of the human breast remains problematical. While oestrogens may cause cystic lesions and epithelial proliferation in the mammary glands of experimental animals and certain progestogens (chlormadinone acetate and medroxyprogesterone acetate) may induce severe myoepithelial hyperplasia in beagles, the classical oral contraceptives (oestrogens and progestogens) reduce the incidence of fibrocystic breast disease in women. The role of prolactin in human breast disease is far from clear despite the fact that in rodents mammary tumors fail to develop following oestrogen administration in the absence of prolactin. Because women with gross cystic disease of the breast are at four times greater risk of developing malignant breast disease, it is felt that the administration of courses of danazol, an impeded androgen derived from the progestin, 17 alpha-ethinyl testosterone, has proved effective in lessening fibrocystic disease of the breast, frequently obviating the need for breast biopsy. The study of the hormonal content of fluid aspirated from gross breast cysts should help elucidate the pathophysiology of breast disease. Breast cyst fluid is rich in androgens, particularly dehydroepiandrosterone sulfate; concentrations of polypeptide hormones like FSH, LH, TSH, PRL, and calcitonin are invariably present sometimes in less and at other times in greater amounts than that found in plasma. Of particular interest is the finding of measurable levels of beta-hCG in cyst fluid but not in the serum. The question arises whether the beta-hCG is biologically active or are the assay values merely the expression of radioimmunoassayable components? Preliminary (as yet unpublished) studies reveal excellent bioactivity as measured by testosterone production in Leydig cell cultures. Time will tell whether elevated levels of bioactive beta-hCG portend neoplastic potential.

Hall LC, Salazar EP, Kane SR, Liu N - "Effects of thyroid hormones on human breast cancer cell proliferation" J Steroid Biochem Mol Biol 109(1-2):57-66 (2008)

The involvement of estrogens in breast cancer development and growth has been well established. However, the effects of thyroid hormones and their combined effects with estrogens are not well studied. We investigated the response of human breast cancer cells to thyroid hormone, particularly the role of T3 in mediating cell proliferation and gene expression. We demonstrated that 17beta-estradiol (E2) or triiodothyronine (T3) promoted cell proliferation in a dose-dependent manner in both MCF-7 and T47-D cell lines. The E2- or T3-dependent cell proliferation was suppressed by co-administration of the ER antagonist ICI. We also demonstrated that T3 could enhance the effect of E2 on cell proliferation in T47-D cells. Using an estrogen response element (ERE)-mediated luciferase assay, we determined that T3 was able to induce the activation of ERE-mediated gene expression in MCF-7 cells, although the effects were much weaker than that induced by E2. These results suggest that T3 can promote breast cancer cell proliferation and increase the effect of E2 on cell proliferation in some breast cancer cell lines and thus that T3 may play a role in breast cancer development and progression.

Kapdi CC, Wolfe JN - "Breast cancer. Relationship to thyroid supplements for hypothyroidism" JAMA 236(10):1124-7 (1976)

This study was undertaken to determine the relationship between thyroid supplements and breast cancer. The incidence of breast cancer among the patients who received thyroid supplements was 12.13%, while in the control group it was 6.2%. The incidence rate of breast cancer was 10%, 9.42%, and 19.48% among patients who received thyroid supplements for one to five, 5 to 15, and for more than 15 years, respectively. The incidence of breast cancer among nulliparous women who received thyroid supplements was 33%, while in the nulliparous women without thyroid supplements the incidence was only 9.25%. Even in a specific age group, the incidence rate of breast cancer was higher.

Kuijpens JL, Nyklíctek I, Louwman MW, Weetman TA, Pop VJ, Coebergh JW - "Hypothyroidism might be related to breast cancer in post-menopausal women" Thyroid 15(11):1253-9 (2005)

An association between breast cancer and thyroid (autoimmune) diseases or the presence of thyroid peroxidase antibodies (TPOAb; a marker of thyroid autoimmune disease) has been suggested. However, little is known about whether women with thyroid (autoimmune) diseases are at increased risk for developing breast cancer. This cross-sectional and prospective cohort study investigated whether the presence of TPOAb or thyroid dysfunction is related to the presence or development of breast cancer. An unselected cohort of 2,775 women around menopause was screened for the thyroid parameters thyrotropin (TSH), free thyroxine (FT(4)), and TPOAb during 1994. Detailed information on previous or actual thyroid disorders and breast cancer, and on putative factors related to breast cancer and thyroid disorders, was obtained. Clinical thyroid dysfunction was defined by both abnormal FT4 and TSH, and subclinical thyroid dysfunction by abnormal TSH (with normal FT4). A TPOAb concentration >or= 100 U/ml was defined as positive (TPOAb(+)). The study group was linked with the Eindhoven Cancer Registry to detect all women with (in situ) breast cancer (ICD-O code 174) diagnosed between 1958 and 1994. Subsequently, in the prospective study, all women who did not have breast cancer in 1994 (n = 2,738) were followed up to July, 2003, and all new cases of (in situ) breast cancer and all cancer-related deaths were registered. Of the 2,775 women, 278 (10.0%) were TPOAb(+). At the 1994 screening, 37 women (1.3%) had breast cancer. TPOAbs were (independently) related to a current diagnosis of breast cancer (OR = 3.3; 95% CI 1.3-8.5). Of the remaining women, 61 (2.2%) developed breast cancer. New breast cancer was related to: (1) an earlier diagnosis of hypothyroidism (OR = 3.8; 95% CI 1.3-10.9); (2) the use of thyroid medication (OR = 3.2; 95% CI 1.0-10.7); and (3) low FT4 (lowest tenth percentile: OR = 2.3; 95% CI 1.2-4.6). In the first 3 years follow up, the relationship between FT4 and log-TSH was disturbed in women with a new breast cancer diagnosis. The presence of TPOAb was not related to breast cancer during follow-up. A direct relationship between thyroid autoimmunity and breast cancer is unlikely. Hypothyroidism and low-normal FT4 are related with an increased risk of breast cancer in post-menopausal women. Studies are needed to clarify the origins of this possible association.

Macejová D, Líska J, Brtko J - "Mammary gland carcinoma-related increase of type I iodothyronine 5'-deiodinase activity in Sprague-Dawley rats" Gen Physiol Biophys 20(3):293-302 (2001)

Type I, iodothyronine 5'-deiodinase (5'-DI) catalyses deiodination of the prohormone thyroxine (T4) to the metabolically active 3,5,3'-triiodo-L-thyronine (T3). The present study was undertaken to investigate the activity of 5'-DI in rat mammary gland tumours representing various combinations of histologically defined papillary, cribriform or comedo patterns of ductal carcinomas. Female Sprague-Dawley rats were given two doses 50 mg x kg(-1) 1-methyl-1-nitrosourea (MNU) in abdominal parts on the 52nd day and 113th day of age. We have found that in comparison with non-lactating mammary gland, the activity of 5'-DI in all mammary gland tumours studied was significantly (p < 0.0001) increased and that the 5'-DI activity, expressed as pmol of 125I- released per min and per mg of protein, in malignant mammary gland tumours was found to be at least two order higher than that of intact mammary non-lactating gland. From our data, we suggest that thyroid hormone in mammary gland tumours might play a significant role to support high energetic expenditure of neoplastic tissues.

Mardaleishvili KG, Nemsadze GG, Metreveli DS, Roinishvili TL - "About correlation of dysfunction of the thyroid gland with fibrocystic diseases in women" Georgian Med News (140):30-2 (2006)

The reference data contain a lot of information on the interrelation between destroying of a thyroid gland and fibrocystic diseases. However contradictions in these data proves that this issue is not solved completely. The aim of the given study was the investigation of interrelations between frequency of occurrence of pathology of a functional condition of the thyroid gland and the frequency of occurrence of fibrocystic diseases. 90 women aged 23-50 were investigated. Concentration of thyroxin (FT4), thyrotrophic hormone (TSH), titers of antibodies to thyreoperoxidase, microsomal fraction of thyreocytes and thyreoglobulin were measured by ELISA. Palpation and ultrasonic investigations of thyroid and mammary glands were used, morphology of central formations of mammary glands according to indications was also carried out. A special questionnaire was completed for each patient. Our investigations showed that along with the declining of function of thyroid gland and the increased level of TSH in the blood, the risk of development of fibrocystic diseases is increased twice.

Martínez L, Castilla JA, Gil T, Molina J, Alarcón JL, Marcos C, Herruzo A - "Thyroid hormones in fibrocystic breast disease." Eur J Endocrinol. 132(6):673-6 (1995)

This study was undertaken to evaluate the role of thyroid hormones in fibrocystic breast disease. The concentrations of thyroid-stimulating hormone (TSH), thyroxine (T4), free T4 and free triiodothyronine (T3) were determined in serum of 50 women with fibrocystic breast disease without macrocysts (cysts of over 3 mm diameter) and in the serum and breast cyst fluid (BCF) of 60 women with fibrocystic breast disease and macrocysts. Possible relationships between thyroid hormones and estradiol, dehydroepiandrosterone sulfate, testosterone, progesterone and 17-hydroxyprogesterone in the BCF also were analyzed. Serum thyroid hormone levels did not differ between the two groups. Free T3 levels were higher in BCF than in serum (p < 0.001), whereas T4, free T4 and TSH concentrations were lower in BCF as compared to serum (p < 0.001). Cysts were divided according to their K+/Na+ ratio because a ratio above 3 represents a predictor of malignant transformation. Free T3 concentrations were higher in BCF than in serum, in both low K+/Na+ cysts and in cysts with a K+/Na+ ratio above 3; those cysts with a high K+/Na+ ratio had the highest free T3 concentration. Free T3 in cysts correlated positively to the K+/Na+ ratio (r = 0.831; p < 0.001). Multiple linear regression analysis demonstrated that the concentration of free T3 in BCF was predicted statistically by the positive regression coefficient for the estradiol concentration. No candidate variable was included in the model to predict concentrations of TSH, free T4 or T4 in BCF. These data suggest an important role of free T3 in the physiology of fibrocystic breast disease.

Mittra I - "Potency of thyroid hormone analogues in suppressing prolactin-mediated mammary growth in thyroidectomized rats" Experientia 31(10):1218-21 (1975)

An antagonism between prolactin and thyroxine, similar to that found in amphibian tissues at metamorphosis, has been recently shown to occur at the level of the rat mammary epithelium. This phenomenon may be implicated in the pathogenesis of human breast cancer. This experiment demonstrates that two analogues of thyroid hormone, triiodothyropropionic acid and triiodothyroacetic acid, which are relatively very weak in their calorigenic action, are as potent as thyroxine and triiodothyronine in inhibiting the prolactin-mediated mammary growth in thyroidectomized rats. The possible implication of this finding in the treatment of mammary cancer is discussed.

Parmeggiani D, Malinconico FA, Moccia G, Idà DN, Ripa C, Scala R, Foroni F, Gilio F, Cognetti C, Iside G, Agresti M - "Hormonal therapy in oncologic treatment: pathogenic hypotheses and interactions between thyroid and breast pathologies" Tumori. 89(4 Suppl):215-9 (2003)

INTRODUCTION: The aim to individuate the eventual correlation between the two pathologies has justified deeper studies to achieve new prospective approaches for both disease. BACKGROUND: We have selected 4 groups of patients who presented an association between the two pathologies: a) malignant breast pathology associated to a malignant thyroid pathology, b) patients with breast carcinoma who presented association with some thyroid alterations, c) patients with thyroid carcinoma who presented association with some breast alterations, d) patients who presented some associations between benign breast pathology and benign thyroid pathology. MATERIALS AND METHODS: We have excluded all patients with a clear physiological or surgical menopausal status, and we've so considered only patients with a regular menstrual cycle. We've so selected a group of 120 patients and we've performed in all these patients during the early follicular phase the following exams: breast echographic evaluation and thyroid echographic-structure and volume determination and finally hormonal determinations we have so obtained two breast subgroups: 32 patients with hyperestrogenic integrative hormonal characteristics, 28 patients subjected to adjuvant hormonal therapy with hypoestregenic hormonal status and finally two thyroid subgroups, 22 patients showing clinical or subclinical hypothyroidism, 38 patients showing clinical or subclinical hyperthyroidism. We've compared these data to a random age-matched health control women group of 25 patients. RESULTS: The first group of patient showed a thyroid hormonal pattern of subclinical hypothyroidism or at least free T3 and free T4 mean value currently under and TSH and TPO Ab levels curve currently over the mean values of the control group. The second group showed the TSH suppressed with free T3 and free T4 curves currently over the mean value of the control group. The third group showed slight elevations in serum PRL levels curve. The fourth group showed increased estrogen levels-curve, often over the mean value of the control group. CONCLUSION: How much is it allowed to perform an hormonal therapy, specially for a benign pathology if we're not yet able to understand the deep and unknown interaction between breast and thyroid?

Pavic Z, Pavic S - "Thyroid function and menopausal status in benign and malignant breast diseases" Med Pregl 48(7-8):231-3 (1995)

Thyroid function was evaluated in premenopausal (healthy controls n = 7, benign breast disease n = 59, primary breast cancer n = 7) and postmenopausal (healthy controls n = 8, benign breast disease n = 51, primary breast cancer n = 10) groups of female subjects. The following parameters were measured: T3, T4, FT3I, FT3I, T3U and TSH. Except significantly higher concentration of T3 in postmenopausal healthy controls (179.6 +/- 32.9 vs. 152.3 +/- 22.4 p < 0.05), in benign and malignant breast lesions there was not any significant deviation. T3U, FT3I and FT4I did not significantly differ in relation to menopausal status. Basal TSH level was premenopausally higher in all groups, but with statistically significant difference within the group of primary breast cancer (0.98 +/- 0.22 vs. 0.47 +/- 0.17 p < 0.05). Consequently, pathologic variations of thyroid hormones plasma level together with the changes of activities of thyrotropin cells could be a significant factor in premenopausal mammary tumorigenesis, while in benign breast lesions a possible relation between thyroid hormone instability and menopausal status was not identified.

Saraiva PP, Figueiredo NB, Padovani CR, Brentani MM, Nogueira CR - "Profile of thyroid hormones in breast cancer patients" Braz J Med Biol Res 38(5):761-5 (2005)

Estrogen involvement in breast cancer has been established; however, the association between breast cancer and thyroid diseases is controversial. Estrogen-like effects of thyroid hormone on breast cancer cell growth in culture have been reported. The objective of the present study was to determine the profile of thyroid hormones in breast cancer patients. Serum aliquots from 26 patients with breast cancer ranging in age from 30 to 85 years and age-matched normal controls (N = 22) were analyzed for free triiodothyronine (T3F), free thyroxine (T4F), thyroid-stimulating hormone (TSH), antiperoxidase antibody (TPO), and estradiol (E2). Estrogen receptor ss (ERss) was determined in tumor tissues by immunohistochemistry. Thyroid disease incidence was higher in patients than in controls (58 vs 18%, P < 0.05). Subclinical hyperthyroidism was the most frequent disorder in patients (31%); hypothyroidism (8%) and positive anti-TPO antibodies (19%) were also found. Subclinical
hypothyroidism was the only dysfunction (18%) found in controls. Hyperthyroidism was associated with postmenopausal patients, as shown by significantly higher mean T3 and T4 values and lower TSH levels in this group of breast cancer patients than in controls. The majority of positive ERss tumors were clustered in the postmenopausal patients and all cases presenting subclinical hyperthyroidism in this subgroup concomitantly exhibited Erss-positive tumors. Subclinical hyperthyroidism was
present in only one of 6 premenopausal patients. We show here that postmenopausal breast cancer patients have a significantly increased thyroid hormone/E2 ratio (P < 0.05), suggesting a possible tumor growth-promoting effect caused by this misbalance.

Yokoe T, Iino Y, Takei H, Horiguchi J, Koibuchi Y, Maemura M, Ohwada S, Morishita Y - "Relationship between thyroid-pituitary function and response to therapy in patients with recurrent breast cancer" Anticancer Res 16(4A):2069-72 (1996)

In this study, thyroid (T3, T4, free T3, free T4) and pituitary function (thyrotropin (TSH), growth hormone (GH), prolactin (PRL)) in 38 patients with recurrent breast cancer were examined. The patients were divided into three groups according to their response to the therapy. There were 16 partial response (PR), 10 no change (NC) and 11 progressive disease (PD) patients. The maximum and the minimum value for each hormone throughout the course of treatment were compared between three groups. The PD group showed significantly lower minimum T3 levels than the other two groups (p < 0.05). The maximum TSH level in the PD group was significantly higher than that of the other groups. The minimum TSH level in the PD group was significantly lower than that in the PR group (p < 0.05).The minimum TSH level in the NC group was also lower than that in the PR group. The maximum PRL level in the NC and the PD group was higher than that in the PR group (p < 0.05, p < 0.01, respectively). The tumors of the patients with temporal increase of TSH level were resistant to all subsequent therapies. These five patients died within four months followed by decreasing of the TSH level. It is concluded that thyroid
and pituitary function, especially free T4, TSH and PRL, are predictive indicators of therapeutic response and the prognosis of the patients with recurrent breast cancer.

Zych F, Mizia-Stec K, Mucha Z, Zych-Twardowska E - "Fibrocystic disease of breast and pituitary-thyroid axis function"
Pol Merkur Lekarski 1(4):227-8 (1996) [Article in Polish]

The aim this study was to report findings on the concentrations of mean triiodothyroxine (T3), thyroxin (T4), thyroid stimulating hormone (TSH) and prolactin (Prl) in patients with benign mastopathy and in control group. All of the examined subjects were clinically euthyroid. The mean T4 concentrations in women with mastopathy (78.25 +/- 15.27 ng/ml) were
significantly lower than in control group 88.73 +/- 15.27). The mean TSH and PRL concentration in women with mastopathy were higher, but not significantly, than in control women. This results indicate, that benign mastopathy seems to be connected with thyroid functions.
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RAS, Thyroid Hormones & Breast Cancer

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Carrera-González MP, Ramírez-Expósito MJ, Mayas MD, García MJ, Martínez-Martos JM - "Local thyroid renin-angiotensin system in experimental breast cancer" Life Sci 93(25-26):1004-9 (2013) doi: 10.1016/j.lfs.2013.10.018. Epub 2013 Oct 29. PMID: 24177601

An association between breast cancer and thyroid dysfunction exists although the underlying mechanisms remain to be elucidated. Numerous studies have characterized the role of thyroid hormones in controlling the synthesis and secretion of renin-angiotensin system (RAS) components, but little information is available on the putative role of the local RAS on thyroid function.

Aims: Here we analyze several soluble and membrane-bound RAS-regulating aminopeptidase activities in thyroid gland from rats with mammary tumors and the relationship with the circulating levels of thyroid stimulating hormone (TSH) and free thyroxin (fT4).

Main methods: We analyze soluble and membrane-bound RAS-regulating aminopeptidase activities fluorometrically using their corresponding aminoacyl-β-naphthylamide as the substrate.

Key findings: We have found in rats with mammary tumors a concomitant change of thyroid RAS-regulating enzymes and thyroid hormone production.

Significance: We suggest that existence of alterations in the regulatory mechanisms mediated by the angiotensins of the local tissue RAS as a consequence of the carcinogenic process which could act alone or in combination with alterations at a higher level of regulation such as the hypothalamus-pituitary axis.

Keywords: Breast cancer; N-methyl-nitrosourea; Renin–angiotensin system; Thyroid ... abd2b93276
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