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Methods Inf Med 2007; 46(01): 05-18
DOI: 10.1055/s-0038-1627826
Original Articles
Schattauer GmbH

An Intelligent Data Mining Model Approach for Adverse Effects of Hormone Replacement Therapy

Y. Lee
1   School of Computing and Engineering, University of Missouri – Kansas City, Kansas City, MO, USA
,
K. Dharmala
2   Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri – Kansas City, Kansas City, MO, USA
,
C.H. Lee
2   Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri – Kansas City, Kansas City, MO, USA
› Author Affiliations
Further Information

Publication History

Publication Date:
24 January 2018 (online)

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Summary

Objectives: A number of controversial studies have been reported on the potential risk of breast cancer caused by hormone replacement therapy (HRT). Some studies showed a positive relationship between HRT and breast cancer onset, but other studies have not confirmed these results. To clarify the contradictory outcomes in the relationships between HRT and the onset of breast cancer, we have designed an intelligent data mining model (IDM), which is able to find proper prognostic factors for cancer onset and provides alternate measures in interpretation of outcome of clinical data through hierarchies of attributes.

Methods: Based on the selection criteria, we selected 22 sets of random and case-control studies of the last 15 years, which identified any involvements of HRT with breast cancer. We analyzed the relationship between HRT and breast cancer using an IDM model consisting of data mining algorithms and public domain data mining tools. Prognostic factors which underline the major etiological dispositions of breast cancer were identified.

Results: The variables which are closely associated with cancer onset to some degree are age 60-69, age at menopause 40-49, parity 0, age 40-49, and types of menopause oophorectomy. An implementation of IDM model on overall pooled data indicated that there is no significant relationship between breast cancer onset and HRT. It is suggested that HRT patients with specific physiological and pathological conditions related with the higher ranks of prognostic factors may have a greater chance to get breast cancer.

Conclusion: The results of this study may guide biomedical research directed at establishing the causal relationships between various medications and their complications, allowing an accurate assessment of efficacy and side effects of new therapeutic treatment in clinical trials without reliance on a large control population.

Keywords

Estrogen - breast cancer - hormone therapy - side effects - risk factor - cohort study - observation study and casecontrol study
 

  • References

  • 1 Belchetz PE. Hormonal treatment of postmenopausal women. N Engl J Med 1994; 330 (Suppl. 15) 1062-71.
    CrossrefPubMedSearch in Google Scholar
  • 2 Lawson JS, Field AS, Tran DD, Houssami N. Hormone replacement therapy use dramatically increases breast oestrogen receptor expression in obese postmenopausal women. Breast Cancer Res 2001; 3 (Suppl. 05) 342-5.
    CrossrefPubMedSearch in Google Scholar
  • 3 Mahavni V, Sood AK. Hormone replacement therapy and cancer risk. Curr Opin Oncol 2001; 13 (Suppl. 05) 384-9.
    CrossrefPubMedSearch in Google Scholar
  • 4 Levine JP. Long-term estrogen and hormone replacement therapy for the prevention and treatment of osteoporosis. Curr Women Health Rep 2003; 3 (Suppl. 03) 181-6.
    PubMedSearch in Google Scholar
  • 5 Zacharieva S, Shigarminova R, Nachev E, Kamenov Z, Atanassova I, Orbetzova M. et al. Effect of amlodipine and hormone replacement therapy on blood pressure and bone markers in menopause. Methods Find Exp Clin Pharmacol 2003; 25 (Suppl. 03) 209-13.
    CrossrefPubMedSearch in Google Scholar
  • 6 Grady D, Rubin SM, Petitti DB, Fox CS, Black D, Ettinger B. et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med 1992; 117 (Suppl. 12) 1016-37.
    CrossrefPubMedSearch in Google Scholar
  • 7 Grodstein F, Stampfer MJ, Manson JE, Colditz GA, Willett WC, Rosner B. et al. Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. N Engl J Med 1996; 335 (Suppl. 07) 453-61.
    CrossrefPubMedSearch in Google Scholar
  • 8 Kuttenn F, Gerson M, de Ligneres B. Effects of hormone replacement therapy in menopause on cardiovascular risk. Need for a European study. Presse Med 2002; 31 (Suppl. 10) 468-75.
    PubMedSearch in Google Scholar
  • 9 Stevenson JC. Hormone therapy and heart disease. Lancet 2002; 359 9308 795-6.
    CrossrefPubMedSearch in Google Scholar
  • 10 Bush TL, Cowan LD, Barrett-Connor E, Criqui MH, Karon JM, Wallace RB. et al. Estrogen use and all-cause mortality. Preliminary results from the Lipid Research Clinics Program Follow-Up Study. Jama 1983; 249 (Suppl. 07) 903-6.
    CrossrefPubMedSearch in Google Scholar
  • 11 Bartelink H, Horiot JC, Poortmans P, Struikmans H, Van den Bogaert W, Barillot I. et al. Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. N Engl J Med 2001; 345 (Suppl. 19) 1378-87.
    CrossrefPubMedSearch in Google Scholar
  • 12 Bottaci L, Drew PJ, Hartley JE, Hadfield MB, Farouk R, Lee PW. et al. Artificial neural networks applied to outcome prediction for colorectal cancer patients in separate institutions. Lancet 1997; 350 9076 469-72.
    CrossrefPubMedSearch in Google Scholar
  • 13 Pike MC, Krailo MD, Henderson BE, Casagrande JT, Hoel DG. ‘Hormonal’ risk factors, ‘breast tissue age’ and the age-incidence of breast cancer. Nature 1983; 303 5920 767-70.
    CrossrefPubMedSearch in Google Scholar
  • 14 McPherson K, Steel CM, Dixon JM. ABC of breast diseases. Breast cancer – epidemiology, risk factors, and genetics. Bmj 2000; 321 7261 624-8.
    CrossrefPubMedSearch in Google Scholar
  • 15 Kelsey JL, Gammon MD, John EM. Reproductive factors and breast cancer. Epidemiol Rev 1993; 15 (Suppl. 01) 36-47.
    CrossrefPubMedSearch in Google Scholar
  • 16 Humphries KH, Gill S. Risks and benefits of hormone replacement therapy: the evidence speaks. Cmaj 2003; 168 (Suppl. 08) 1001-10.
    PubMedSearch in Google Scholar
  • 17 ACS.. American Cancer Society – Cancer facts and figures. 2002
    PubMedSearch in Google Scholar
  • 18 Ursin G, Tseng CC, Paganini-Hill A, Enger S, Wan PC, Formenti S. et al. Does menopausal hormone replacement therapy interact with known factors to increase risk of breast cancer?. J Clin Oncol 2002; 20 (Suppl. 03) 699-706.
    CrossrefPubMedSearch in Google Scholar
  • 19 Salmon RJ, Ansquer Y, Asselain B, Languille O, Lesec G, Remvikos Y. Clinical and biological characteristics of breast cancers in post-menopausal women receiving hormone replacement therapy for menopause. Oncol Rep 1999; 6 (Suppl. 03) 699-703.
    PubMedSearch in Google Scholar
  • 20 Gapstur SM, Morrow M, Sellers TA. Hormone replacement therapy and risk of breast cancer with a favorable histology: results of the Iowa Women’s Health Study. Jama 1999; 281 (Suppl. 22) 2091-7.
    CrossrefPubMedSearch in Google Scholar
  • 21 Muti P, Quattrin T, Grant BJ, Krogh V, Micheli A, Schunemann HJ. et al. Fasting glucose is a risk factor for breast cancer: a prospective study. Cancer Epidemiol Biomarkers Prev 2002; 11 (Suppl. 11) 1361-8.
    PubMedSearch in Google Scholar
  • 22 Karande AA, Sridhar L, Gopinath KS, Adiga PR. Riboflavin carrier protein: a serum and tissue marker for breast carcinoma. Int J Cancer 2001; 95 (Suppl. 05) 277-81.
    CrossrefPubMedSearch in Google Scholar
  • 23 Daly MB, Lerman CL, Ross E, Schwartz MD, Sands CB, Masny A. Gail model breast cancer risk components are poor predictors of risk perception and screening behavior. Breast Cancer Res Treat 1996; 41 (Suppl. 01) 59-70.
    CrossrefPubMedSearch in Google Scholar
  • 24 Hopke PK, Liu C, Rubin DB. Multiple imputation for multivariate data with missing and belowthreshold measurements: time-series concentrations of pollutants in the Arctic. Biometrics 2001; 57 (Suppl. 01) 22-33.
    CrossrefPubMedSearch in Google Scholar
  • 25 Bohning D. Meta-analysis: a unifying meta-likelihood approach framing unobserved heterogeneity, study covariates, publication bias, and study quality. Methods Inf Med 2005; 44 (Suppl. 01) 127-35.
    Thieme ConnectPubMedSearch in Google Scholar
  • 26 Budde T, Haude M, Hopp HW, Kerber S, Caspari G, Fassbender G. et al. A prognostic computer model to predict individual outcome in interventional cardiology. The INTERVENT Project. Eur Heart J 1997; 18 (Suppl. 10) 1611-9.
    CrossrefPubMedSearch in Google Scholar
  • 27 Jha BK TS, Kulkarni BD. Estimating diffusion coefficients of micellar system using an ANN. J Coll I Sci 1995; 170: 392-8.
    PubMedSearch in Google Scholar
  • 28 Hussain AS, Yu XQ, Johnson RD. Application of neural computing in pharmaceutical product development. Pharm Res 1991; 8 (Suppl. 10) 1248-52.
    CrossrefPubMedSearch in Google Scholar
  • 29 Achanta AS, KJ JK, Rhodes CT. Artificial neural network: implications for pharmaceutical sciences. Drug Dev Ind Pharm 1995; 21: 19-55.
    CrossrefPubMedSearch in Google Scholar
  • 30 Petitti D.B.. Meta-Analysis, Decision Analysis, and Cost Effectiveness Analysis: Methods for Quantitative Synthesis in Medicine. 1994
    PubMedSearch in Google Scholar
  • 31 Blettner M, Sauerbrei W, Schlehofer B, Scheuchenpflug T, Friedenreich C. Traditional reviews, meta-analyses and pooled analyses in epidemiology. Int J Epidemiol 1999; 28 (Suppl. 01) 1-9.
    CrossrefPubMedSearch in Google Scholar
  • 32 Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D. et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. Jama 2000; 283 (Suppl. 15) 2008-12.
    CrossrefPubMedSearch in Google Scholar
  • 33 LeLorier J, Gregoire G, Benhaddad A, Lapierre J, Derderian F. Discrepancies between metaanalyses and subsequent large randomized, controlled trials. N Engl J Med 1997; 337 (Suppl. 08) 536-42.
    CrossrefPubMedSearch in Google Scholar
  • 34 Attia J, Thakkinstian A, D’Este C. Meta-analyses of molecular association studies: methodologic lessons for genetic epidemiology. J Clin Epidemiol 2003; 56 (Suppl. 04) 297-303.
    CrossrefPubMedSearch in Google Scholar
  • 35 Garbe E, Levesque L, Suissa S. Variability of breast cancer risk in observational studies of hormone replacement therapy: a meta-regression analysis. Maturitas 2004; 47 (Suppl. 03) 175-83.
    CrossrefPubMedSearch in Google Scholar
  • 36 Bott OJ, Ammenwerth E, Brigl B, Knaup P, Lang E, Pilgram R. et al. The challenge of ubiquitous computing in health care: technology, concepts and solutions. Findings from the IMIA Yearbook of Medical Informatics 2005. Methods Inf Med 2005; 44 (Suppl. 03) 473-9.
    Thieme ConnectPubMedSearch in Google Scholar
  • 37 Singh SVV, Vaghani B, Drake B, Lee Y. Feature Based Image Classification and Labeling in Pediatric Echocardiogram. Kansas City Lifesciences Research Day 2004
    PubMedSearch in Google Scholar
  • 38 Terry PD, Miller AB, Rohan TE. Prospective cohort study of cigarette smoking and colorectal cancer risk in women. Int J Cancer 2002; 99 (Suppl. 03) 480-3.
    CrossrefPubMedSearch in Google Scholar
  • 39 Pyne S. Air pollution.. Small particles add up to big disease risk. Science 2002; 295 5562 1994.
    PubMedSearch in Google Scholar
  • 40 Brin S, Motwani R, Silverstein C. Beyond market baskets: Generalizing association rules to correlation. Proc of the ACM Conference on Management of Data 1997
    PubMedSearch in Google Scholar
  • 41 Dickens C, McGowan L, Dale S. Impact of depression on experimental pain perception: a systematic review of the literature with meta-analysis. Psychosom Med 2003; 65 (Suppl. 03) 369-75.
    CrossrefPubMedSearch in Google Scholar
  • 42 Fayyad UM, Piatetsky-Shapiro G, Smyth P. From data mining to knowledge discovery: an overview. Advances in Knowledge Discovery and Data Mining. AAAI/MIT Press: 1996. pp 1-34.
    Search in Google Scholar
  • 43 Mehta M, Agrawal R, Rissanen J. SLIQ: a fast scalable classifier for data mining. Prog 5th Int Conf Extending Database Technology (EDBT-96); 1996
    PubMedSearch in Google Scholar
  • 44 Perez-Enciso MTM. Prediction of clinical outcome with microarray data: a partial least squares discriminant analysis (PLS-DA) approach. Hum Genet 2003; 112 5-6 581-92.
    PubMedSearch in Google Scholar
  • 45 Mannila H, Räihä K. Algorithms for inferring functional dependencies from relations. Data & Knowledge Engineering archive 1994; 12 (Suppl. 01) 83-99.
    PubMedSearch in Google Scholar
  • 46 Agrawal R, Imielinski T, Swami A. Mining association rules between sets of items in large databases. Proceeding of the ACM SIGMOD Conference on Management of Data 1993; 207-16.
    PubMedSearch in Google Scholar
  • 47 Fabrizi F, Martin P, Dixit V, Bunnapradist S, Dulai G. Meta-analysis: the effect of age on immunological response to hepatitis B vaccine in endstage renal disease. Aliment Pharmacol Ther 2004; 20 (Suppl. 10) 1053-62.
    CrossrefPubMedSearch in Google Scholar
  • 48 Kuscu NK, Toprak AB, Vatansever S, Koyuncu FM, Guler C. Tear function changes of postmeno- pausal women in response to hormone replacement therapy. Maturitas 2003; 44 (Suppl. 01) 63-8.
    CrossrefPubMedSearch in Google Scholar
  • 49 Uint L, Gebara OC, Pinto LB, Wajngarten M, Boschcov P, da Luz PL. et al. Hormone replacement therapy increases levels of antibodies against heat shock protein 65 and certain species of oxidized low density lipoprotein. Braz J Med Biol Res 2003; 36 (Suppl. 04) 491-4.
    CrossrefPubMedSearch in Google Scholar
  • 50 Yilmazer M, Fenkci V, Fenkci S, Aktepe O, Sonmezer M, Kurtay G. Association of serum complement (C3, C4) and immunoglobulin (IgG, IgM) levels with hormone replacement therapy in healthy post-menopausal women. Hum Reprod 2003; 18 (Suppl. 07) 1531-5.
    CrossrefPubMedSearch in Google Scholar
  • 51 Witte S, Victor N. Some problems with the investigation of noninferiority in meta-analysis. Methods Inf Med 2004; 43 (Suppl. 05) 470-4.
    Thieme ConnectPubMedSearch in Google Scholar
  • 52 Schairer C, Gail M, Byrne C, Rosenberg PS, Sturgeon SR, Brinton LA. et al. Estrogen replacement therapy and breast cancer survival in a large screening study. J Natl Cancer Inst 1999; 91 (Suppl. 03) 264-70.
    CrossrefPubMedSearch in Google Scholar
  • 53 Heer K, Kumar H, Read JR, Fox JN, Monson JR, Kerin MJ. Serum vascular endothelial growth factor in breast cancer: its relation with cancer type and estrogen receptor status. Clin Cancer Res 2001; 7 (Suppl. 11) 3491-4.
    PubMedSearch in Google Scholar
  • 54 van Diest PJ, Michalides RJ, Jannink L, van der Valk P, Peterse HL, de Jong JS. et al. Cyclin D1 expression in invasive breast cancer. Correlations and prognostic value. Am J Pathol 1997; 150 (Suppl. 02) 705-11.
    PubMedSearch in Google Scholar
  • 55 Polychemotherapy for early breast cancer: an overview of the randomised trials.. Early Breast Cancer Trialists’ Collaborative Group. Lancet 1998; 352 9132 930-42.
    CrossrefPubMedSearch in Google Scholar
  • 56 Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group. Lancet 1998; 351 9114 1451-67.
    CrossrefPubMedSearch in Google Scholar
  • 57 DiSaia PJ, Brewster WR, Ziogas A, Anton-Culver H. Breast cancer survival and hormone replacement therapy: a cohort analysis. Am J Clin Oncol 2000; 23 (Suppl. 06) 541-5.
    CrossrefPubMedSearch in Google Scholar
  • 58 Malone KE, Daling JR, Thompson JD, O’Brien CA, Francisco LV, Ostrander EA. BRCA1 mutations and breast cancer in the general population: analyses in women before age 35 years and in women before age 45 years with first-degree family history. Jama 1998; 279 (Suppl. 12) 922-9.
    CrossrefPubMedSearch in Google Scholar
  • 59 Chen CL, Weiss NS, Newcomb P, Barlow W, White E. Hormone replacement therapy in relation to breast cancer. Jama 2002; 287 (Suppl. 06) 734-41.
    CrossrefPubMedSearch in Google Scholar
  • 60 Colditz GA, Hankinson SE, Hunter DJ, Willett WC, Manson JE, Stampfer MJ. et al. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med 1995; 332 (Suppl. 24) 1589-93.
    CrossrefPubMedSearch in Google Scholar
  • 61 Palmer JR, Rosenberg L, Clarke EA, Miller DR, Shapiro S. Breast cancer risk after estrogen replacement therapy: results from the Toronto Breast Cancer Study. Am J Epidemiol 1991; 134 (Suppl. 12) 1386-95. discussion 96-401.
    CrossrefPubMedSearch in Google Scholar
  • 62 Kaufman DW, Palmer JR, de Mouzon J, Rosenberg L, Stolley PD, Warshauer ME. et al. Estrogen replacement therapy and the risk of breast cancer: results from the case-control surveillance study. Am J Epidemiol 1991; 134 (Suppl. 12) 1375-85.
    CrossrefPubMedSearch in Google Scholar
  • 63 Schuurman AG, van den Brandt PA, Goldbohm RA. Exogenous hormone use and the risk of postmenopausal breast cancer: results from The Netherlands Cohort Study. Cancer Causes Control 1995; 6 (Suppl. 05) 416-24.
    CrossrefPubMedSearch in Google Scholar
  • 64 Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53,297 women with breast cancer and 100,239 women without breast cancer from 54 epidemiological studies. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet 1996; 347 9017 1713-27.
    CrossrefPubMedSearch in Google Scholar
  • 65 Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet 1997; 350 9084 1047-59.
    CrossrefPubMedSearch in Google Scholar
  • 66 Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet 2001; 358 9291 1389-99.
    CrossrefPubMedSearch in Google Scholar
  • 67 Cuzick J, Forbes J, Edwards R, Baum M, Cawthorn S, Coates A. et al. First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial. Lancet 2002; 360 9336 817-24.
    CrossrefPubMedSearch in Google Scholar