Liver Function Analysis in Patients with Carcinoma Breast under Radiotherapy

A.Anuradha1 Dr. Sobha Devi kolla2, and Dr. Jaganadha Rao Peela3 (1. Research Scholar, Dept. of Human Genetics, Andhra University; Visakhapatnam,2.Associate Professor, Dept. of Biochemistry, Andhra Medical College, 3. Independent researcher, India ) Background: Carcinoma of breast is one of prevalent diseases of Andhra Pradesh, India especially in young females. The existing literature shows that there is a compromise in Liver Function in patients receiving into two groups as Premenopausal (25 nos.) and Postmenopausal (15 nos.) patients. Demarcating age was 47 years, less than 47 years as premenopausal, 47 and higher as post menopausal. Levels of enzymes like Asprtate aminotransferase, Alkaline Alanine Phosphatase,

tamoxiphen therapy and patients receiving hormonal therapy and disease itself. The present paper aims to analyze the liver function in patients undergoing radiotherapy who were suffering from carcinoma of breast. Material and methods: 40 patients with various stages of breast cancer have been selected from department of Radiotherapy (Jan10 to July10), King George Hospital, Visakhapatnam, India. The age group is 16 to 65 years, with mean age of 37 years. There were 21 healthy controls with age group of 20 to 55 years with mean age of 35 years. For analysis purpose, 40 patients were divided

Aminotransferase,

Serum -glutamyl transferase, Serum Total protein and Serum Bilurubin were selected as indicators of Liver function. All the

mentioned enzymes have been analyzed for all patients with overnight fasting. All the tests have been performed by authentic methods available. Results: The liver enzymes AST and ALT were found to be significantly elevated in patients suffering from carcinoma breast compared to controls (p = 0.0001 and 0.01 respectively) in all groups. Alkaline

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phosphatase also found elevated but not significantly over controls. But on

therapy and even after. More study is being taken up to workout the therapeutic

comparison with premenopausal and Post menopausal women, there was a significant rise ( p= 0.031). Serum glutamyl transferase

management using the liver enzyme levels as indicators.

Introduction
found significantly rose in the cases of carcinoma breast when compared to controls (p= 0.006) and Premenopausal women (p= 0.0059) but when the values were compared with postmenopausal women, the rise was not significant. Serum Total proteins and Carcinoma of breast is one of prevalent diseases of Southern Andhra Pradesh, India especially in young females. This is going to be first most common cancer among women pushing carcinoma cervix to the second place which was previously most common cancer among Indian females. In India, the incidence of breast cancer is increasing, with an estimated 80,000 new cases diagnosed annually. Unfortunately most of the cases were diagnosed very late because there is lack of awareness, poor screening and social stigma in reporting about the problem. The burden of breast cancer will continue to grow not only in terms of the absolute number of cases but also in terms of incidence. As mammography will be difficult to implement

Serum Bilirubin didnt show any significant rise among patients with carcinoma breast in both groups. Complete analysis is presented in the full paper. Conclusion: Analysis of Liver Enzymes in 40 patients of carcinoma breast, who underwent radiotherapy, reveals that, there was a significant variation in enzyme levels and these patients were more prone to liver damage. Patients after radical surgery of carcinoma breast need to be managed for maintaining liver function throughout the

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in India for various reasons, efforts should be made to detect breast cancer at an early stage by educating the population about risk factors and through screening by physical

chemotherapy and Radiotherapy. It may be a better prognostic marker in the estimating disease severity and also after therapy [3]. So that assessing liver function is best tool to find disease severity. There are several studies about liver function in carcinoma breast mainly in metastasis and

examination or by self-breast examination. [1] Age specific incidence rates for breast cancer for most of the urban population in India were found to show steep increase till menopause years, after which the curves plateau. Most of the registries data indicate that Christians in India have the greatest risk of breast cancer and Muslims have the lowest rate. In all the populations breast cancer was found to be less prevalent at the lower

chemotherapy. Immunological role is also expected in certain cases during

chemotherapy[4].The present study aims to analyze the liver function in patients

undergoing radiotherapy who are suffering from carcinoma of breast.

Materials and Methods

education level and the incidence increased with the education level. [2] The existing literature shows that there is a compromise in liver function in patients receiving 40 patients with various stages of breast cancer have been selected from department of Radiotherapy (Jan10 to July10), King George Hospital, Visakhapatnam, India. The age group is 16 to 65 years, with mean age of 37 years. There were 21 healthy controls

tamoxiphen therapy and patients receiving hormonal therapy and disease itself.

Hepatotoxicity is one of the common phenomenons in malignant breast disease. It may be due to cancer itself, metastasis,

with age group of 20 to 55 years with mean age of 35 years. For analysis purpose, 40

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patients were divided into two groups as Premenopausal (25 nos.) and Postmenopausal (15 nos.) patients. Demarcating age is 47

post menopausal women, there was a significant rise in post menopausal (p= 0.031). Mean and standard deviation values of premenopausal cases were given in table.2 and post menopausal cases were given in table.3. Serum GGT found significantly rose in the cases of carcinoma breast when compared to controls (p= 0.006) and

years, less than 47 years as premenopausal, 47 and higher as post menopausal. Levels of enzymes like Aspartate aminotransferase AST [5] Alanine Aminotransferase ALT [6], Alkaline Phosphatase ALP [7], Serum -

Glutamyl Transpeptidase GGT [8], Serum Total proteins [9] and Serum Bilurubin [10] were selected and measured as indicators of Liver function.

Premenopausal women (p= 0.0059) but when the values were compared with

postmenopausal women, the rise was not significant. Serum Total proteins and serum bilirubin didnt show any significant rise

Results
among patients with carcinoma breast both in The liver enzymes AST and ALT and were found to be significantly elevated in patients suffering from carcinoma breast compared to controls (p = 0.0001 and 0.01 respectively) in all groups. The mean and standard deviation values for parameters of total cases were summarized in table.1 ALP also found elevated but not significantly over controls. But on comparison with premenopausal and Early recognition and diagnosis of the etiology of acute liver failure could impact at least short-term survival in carcinoma breast population [13]. There is a significant correlation of estimating liver enzymes preoperatively and also assessment of groups.

Discussion

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metastasis with ultrasound examination [14]. Previous case studies after one year of radiation therapy, the patients presented after evaluation of liver function tests there is elevation of serum AST, serum ALT, GGT, total bilirubin, direct bilirubin and ALP [11, 12]. Elevation of single AST in locally cancer showing much

scan [19, 20]. GGT is a component of the pathways that metabolize glutathione and glutathione-conjugates, the difference in levels of the enzyme in invasive breast cancers may be one explanation for the variation in chemotherapy response that has been observed in patients cancer treated [18]. during for LFT the

advanced breast

advanced

mammary

interest [15] and Multivariate analysis using the Cox model suggested that the degree of elevation of AST was the single most important prognostic factor for survival after the diagnosis of liver metastases [16]. Elevated ALP occurring during

abnormalities

detected

administration of chemotherapy for patients with breast cancer are a manifestation of drug toxicity and that such abnormalities are insufficient evidence of hepatic metastases [21]. Radiation Induced Liver

chemotherapy on the other hand was quite common but more likely due to hepatic toxicity of the drugs. The development of abnormal liver function tests even in

Disease(RILD) is one of the complications of radiotherapy where Abdominal computed tomography scan reveals an abnormal

"straight-border" attenuation of the liver along the trajectory of radiation beam with elevated liver enzymes[22].RILD occurs after 4-8 weeks after radiation exposure[23, 24]. Breast cancer cell-secreted cytokines

association with focal defects on liver scan is not sufficient to diagnose metastatic breast cancer in patients receiving adjuvant

chemotherapy [17]. This is detected much earlier to a positive scintiscan or ultrasound

stimulate macrophages to produce TNF-, a

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known up-regulator of E-selectin expression, and therefore cell adherence to endothelium. Inhibition of this mechanism could be an attractive therapeutic option for the

radiation therapy [11, 12]. ALP is seen more in postmenopausal women than pre

menopausal women. Conclusion: Analysis of Liver Enzymes in 40 patients of carcinoma radiotherapy, breast, reveals who that, underwent there is a

prevention of breast cancer metastasis.[25]. I t is well documented that hepatotoxicity is one of the common feature in breast cancer owing to its metastasis or due to

significant variation in enzyme levels and these patients are more prone to liver damage. Patients after radical surgery of carcinoma breast need to be managed for maintaining liver function throughout the therapy and even after. More study is being taken up to work out the therapeutic management using the liver enzyme levels as indicators. Liver enzymes could be the best prognostic markers in carcinoma breast during and after treatment. References:

chemotherapy but emphasis in present study is on radiotherapy. Current study is

describing there is hepatotoxicity among all patients with more preponderance to

premenopausal women who is suffering from breast cancer who were exposed to

radiotherapy. Despite the precipitating factors like metastasis, chemotherapy and

radiotherapy there is degradation in liver function in all breast cancer patients. AST seems to be one of the enzymes more likely elevated like previous studies [15, 16]. There is no much documentation about liver damage after radiotherapy in breast cancer but there were changes in liver function after

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1.

Murthy NS, Chaudhry K, Nadayil D, Agarwal UK, Saxena S. Changing trends in incidence of breast cancer: Indian scenario. Indian J Cancer 2009; 46:73-4

5.

SchunannG,BonoraR,CeriottiF,FerartG eteal.IFCC primary reference procedure for the measurement of catalytic

activity concentrations of enzymes at 370C . Part5:reference procedure for the measurement of catalytic concentration

2.

.Yeole BB, Kurkure AP. Asian Pac J. An epidemiological assessment of

of Aspartate amino transferase.Clin Chem Lab Med 2002;40:725-33. 6. SchunannG,BonoraR,CeriottiF,FerartG eteal.IFCC primary reference procedure for the measurement of catalytic

increasing incidence and trends in breast cancer in Mumbai and other sites in India, during the last two decades. Cancer Prev. 2003 Jan-Mar;4(1):51-6. 3. L Wyld, E Gutteridge, S E Pinder, J J James, S Y Chan, K L Cheung, J F R Robertson and A J Evans. Prognostic factors for patients with hepatic

activity concentrations of enzymes at 370C . Part5: reference procedure for the measurement of of Alanine catalytic amino

concentration

transferase.Clin Chem Lab Med 2002; 40:718-24 7. Tietz NW,RinkerD,ShawLM.IFCC

metastases from breast cancer. British Journal of Cancer (2003) 89, 284290. doi:10.1038/sj.bjc.6601038. 4. Alessandro Inno, Michele Basso, Fabio M Vecchio, Valentina A Marsico, Eleonora Cerchiaro, Ettore D'Argento, Cinzia Bagal and Carlo Barone. Anastrozole-related acute hepatitis with autoimmune features: a case report. BMC Gastroenterology 2011, 9. 8.

method for alkaline phosphatise.J Clin Chem Clin Biochem 1983;21:731-48. SzaszSzasz, G. Reaction-rate method for g-glutamyltransferase activity in serum, Clin. Chem. 22:2051-2055, 1976. . Doumas, B.T., Bayse, D.D., Carter, R.J., et al. Estimation of serum total proteins. Clin. Chem. 1981; 27:16421650.

11:32doi:10.1186/1471-230X-11-32.

Journal of Basic Medical and Allied Sciences 2012;2:

10.

RandRN,Di easqua A. A new diazo method for the determination of

14.

Clark CP 3rd, Foreman ML, Peters GN, Cheek JH, Sparkman RS. Efficacy of peroperative liver function tests and ultrasound in detecting hepatic

Bilirubin.Clin Chem 1962; 6:570-8 11. Marcelo Madeira, Andr Mattar,

metastasis in carcinoma of the breast. Surg Gynecol Obstet. 1988 Dec;

Rodrigo JB Passos, Caroline D Mora, Luiz HBV Mamede, Viviane H 15.

167(6):510-4. Birtle A, Lawton P, Chaundary M, Richman P, Mcfarlane B. Unexplained high AST in locally advanced breast cancer. Breast J. 2003 Nov-

Kishino, Thomas ZM Torres, Andressa FR de S, Roberto E dos Santos and Luiz H Gebrim, A case report of male breast cancer in a very young patient: What is changing?World Journal of Surgical Oncology 2011, 9:16

Dec;9(6):505-6. 16. O'Reilly SM, Richards MA, Rubens RD. Liver metastases from breast

doi:10.1186/1477-7819-9-16 12. Raktima Goswami, M, Michael

cancer:

the

relationship

between

Babich, MD2 Katie F. Farah, MD2 Occult Masquerading Failure. Breast as Malignancy Acute Hepatic & 17.

clinical, biochemical and pathological features and survival. Eur J Cancer. 1990; 26(5):574-7. Vaughan WP, Wilcox PM, Alderson PO, Ettinger DS, Abeloff MD. Hepatic toxicity of adjuvant chemotherapy for carcinoma of the breast. Med Pediatr Oncol. 1979;7(4):351-9. 18. Durham JR, Frierson HF Jr, Hanigan MH. Gamma-glutamyl transpeptidase immunoreactivity in benign and

Gastroenterology

Hepatology Volume 7, Issue 1 January 2011 pages 62-65 13. Dr. Hector E. Nazario, Metastatic Breast Cancer Presenting as Acute Liver Failure. Gastroenterology &

Hepatology Volume 7, Issue 1 January 2011pages 65-66

malignant breast tissue. Breast Cancer Res Treat. 1997 Aug;45(1):55-62.

Journal of Basic Medical and Allied Sciences 2012;2:

19.

De Rivas L, Coombes RC, McCready VR, et al. Tests for liver metastases in breast cancer: evaluation of liver scan and liver ultrasound. Clin Oncol

24.

Sempoux C, Horsmans Y, Geubel A, et al: Severe radiation-induced liver

disease following localized radiation therapy for biliopancreatic carcinoma: Activation of hepatic stellate cells as an early event. Hepatology 26:128-134, 1997. 25. Eichbaum C, Meyer AS, Wang N, Bischofs E, Steinborn A, Bruckner T, Brodt P, Sohn C, Eichbaum MH. Breast Cancer Cell-derived and Cell Cytokines, Adhesion:

1980;6:225-30 20. A L Hoe FRCS, G T Royle MS FRCS, I Taylor MD. Breast liver metastasesincidence, diagnosis and outcome.

Journal of the Royal Society of Medicine Volume 84 December 1991 pages 714-716. 21. Cynthia A. Larroquette;Gabriel N.

Hortobagyi, MD; Aman U. Buzdar, MD; Frankie A. Holmes, MD.

Macrophages

Implications for Metastasis. Anticancer Res. 2011 Oct; 31(10):3219-27.

Subclinical Hepatic Toxicity during Combination Chemotherapy for Breast Cancer. JAMA 1986; 256:2988-2990. 22. Radwan F. Khozouz, Syed Z. Huq, Michael C. Perry.Radiation-Induced

Liver Disease. Journal of Clinical Oncology, Vol 26, No 29 (October 10), 2008: pp. 4844-4845. 23. . Yamasaki SA, Marn CS, Francis IR, et al: High-dose for localized of radiation hepatic

therapy

treatment

malignant tumors: CT findings and their relation to radiation hepatitis. A J Roentgenol 165:79-84, 1995

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Controls : Table 1
AST Mean cases STD Cases Mean Controls STD Controls 18.53 6.27 11.33 4.45 0.0001 ALT 15.33 7.058 10.32 5.67 0.011 ALK 154.8 72.21 137.11 58.39 0.21 GGT 35.30 16.16 26.76 6.54 0.006 T.P 6.97 0.65 6.95 2.35 0.94 T.BIL 0.56 0.15 0.71 0.22 0.0059

Abbreviations: AST: Aspartate aminotransferase, ALT: Alanine Aminotransferase, ALK: Alkaline Phosphatase, GGT: ansaminase , T.P: Serum Total protein T.Bil: Serum Total Bilurubin

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Table 2. Total Cases

AST 18.53 6.27 0.0001 ALT 15.33 7.06 0.011 ALK 154.80 72.21 0.208 GGT 35.30 16.163 0.006 T.P 6.97 0.655 0.94 T.BIL 0.56 0.15 0.0059

Table 3 Pre-menopausal
AST Mean STD p-Value 17.7 5.14 0.0001 ALT 14.6 6.85 0.0271 ALK 135 52.00 0.9 GGT 36.4 16.40 0.0059 T.P 6.87 0.68 0.6908 T.BIL 0.585 0.15 0.043

Table 4. Post menopausal

AST 20.20 8.15 0.0007 0.312 ALT 16.80 7.61 0.01 0.432 ALK 194.40 92.08 0.0507 0.031 GGT 33.10 16.31 0.113 NS T.P 7.17 0.58 0.77 0.24 T.BIL 0.50 0.15 0.02 NS

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