Assessment of point-of-care testing for prediction of aromatase inhibitor-associated side effects in obese postmenopausal breast cancer patients screened for cardiovascular risk factors
| dc.contributor.advisor | Akudugu, John M. | en_ZA |
| dc.contributor.advisor | Nyasulu, Peter S. | en_ZA |
| dc.contributor.author | Milambo, Jean Paul Muambangu | en_ZA |
| dc.contributor.other | Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics. | en_ZA |
| dc.date.accessioned | 2021-08-17T10:21:11Z | |
| dc.date.accessioned | 2021-12-22T14:13:38Z | |
| dc.date.available | 2021-08-17T10:21:11Z | |
| dc.date.available | 2021-12-22T14:13:38Z | |
| dc.date.issued | 2021-12 | |
| dc.description | Thesis (PhD)--Stellenbosch University, 2021. | en_ZA |
| dc.description.abstract | ENGLISH SUMMARY : Background: Aromatase inhibitors (AIs) constitute a standard of care for post- and premenopausal patients with estrogen receptor-positive breast cancer (BC). Obesity and mediators of inflammation have been identified as the most important risk and predictive factors in postmenopausal breast cancer survivors (BCS) using AIs. However, data on the feasibility of point-of-care (POC) genotyping using high sensitivity C-reactive protein (hs-CRP) and body mass index (BMI) as predictors of drug toxicity among postmenopausal BCS in African clinical settings are lacking. Aim: The study was conducted to assess the impact of AIs on hs-CRP and BMI, which are used at POC for prediction of therapy-associated side effects among obese postmenopausal breast cancer patients in Africa. Methods: One hundred and twenty-six female BC patients with cancer stages ranging from 0-III were recruited at Tygerberg Hospital (TBH) in the Western Cape Province of South Africa, between August 2014 and February 2017, for the study. A Quasi-experimental study was conducted. Patients were initially subjected to AIs and subsequently followed up at months 4, 12, and 24. Baseline clinical and biomedical assessments were conducted at commencement of study to predict hs-CRP and BMI at months 12 and 24, using a multiple imputation model. A random effects model was used to monitor the changes over the time. Statistical analyses were performed using SPSS 18.0 software (SPSS Inc., Chicago, IL, USA) and STATA version 16. Analyses were two-tailed and a p-value < 0.05 was considered statistically significant. Results: The mean age of the participants was 61 years (SD = 7.11 years; 95% CI: 60-62 years). Linear regression revealed that hs-CRP was associated with waist circumference (OR: 7.5; p= 0. 0116; 95%CI: 1.45 to 39.61) and BMI (OR: 2.15; p=0.034, 95%CI: 1.02 to 4.56). Waist circumference was associated with hypertension (OR: 3, 83; p= 0.003, 95%CI: 1.56 to 9.39), and chemotherapy was associated with waist circumference by (p= 0. 016; 95%CI: 0.11 to 0. 79). hs-CRP levels were significantly correlated with BMI and total body fat (TBF) among postmenopausal using aromatase inhibitors. Random linear effects modelling revealed stronger statistical association between BMI and homocysteine (p=0.021, 95%CI: 0.0083 to 0.1029). Weight and TBF were strongly associated after 24 months of follow-up. In addition, hs-CRP was associated with BMI (p=0.0001) and other inflammatory markers such as calcium (p=0.021, 95%CI: 0.0083 to 0.1029), phosphate (p=0.039, 95%CI: 0.0083 to 0.1029), and ferritin (p=0.002, 95%CI: 0.0199 to 0.084). Multiple imputation modelling indicated that there were statistically significant variations in TBF, weight, homocysteine, ferritin, and calcium between baseline and after 24 months of follow-up. Mathematical modeling Comparison of genotyping from HyBeacon® probe technology to Sanger sequencing showed that yielded sensitivity of 99% (95% CI: 94.55 to 99.97%), specificity of 89.44% (95% CI: 87.25 to 91.38%), PPV of 51% (95%: 43.77 to 58.26%), and NPV of 99.88% (95% CI: 99.31 to 100.00%). Based on the mathematical model, the assumptions revealed that incremental cost-effective ratio (ICER) was R7 044.55. Conclusion: This study revealed that hs-CRP and BMI are predictors of CVD-related adverse events in obese postmenopausal patients. Calcium, phosphate, homocysteine, and ferritin should also be incorporated in POCT. There were statistically significant variations in TBF, weight, hs-CRP, BMI, homocysteine, ferritin, and calcium between baseline and after 24 months of follow-up. HyBeacon® probe technology at POC for AI-associated adverse events maybe cost-effective in Africa while adjunct to standard practice. The appropriate pathways for implementation of POC testing in postmenopausal breast cancer survivors need further investigation in different clinical settings with real data for external validation. | en_ZA |
| dc.description.abstract | AFRIKAANSE OPSOMMING : Agtergrond: Aromatase inhibeerders (AIs) konstrueer ‘n standaard van behandeling vir pre- en post-menopouse pasiënte met estrogeen reseptor-positiewe borskanker(BC). Vetsug en bemiddelaars van inflammasie is geïdentifiseer as die mees belangrike risiko en voorspellende faktore in postmenopouse pasiënte wie borskanker oorleef (BCS) deur die gebruik van AIs. Alhoewel, daar is data tekortkominge oor die geskiktheid van versorgingspunt -toetsing van hoë sensitiwiteit C-reaktiewe proteïen(hs-CRP) en liggaamsmassa indeks(BMI) as voorspellers van medikasie toksisiteit onder postmenopouse BCS in die kliniese omgewing van Afrika. Mikpunt: Hierdie studie is uitgevoer om te assesseer wat die impak is van AIs op hs-CRP en BMI versorgingspunt-toetsing op die voorspelling van terapie-geassosieërde newe-effekte onder vetsugtige postmenopouse borskankerpasïente vanaf Augustus 2014 tot en met Februarie 2017 by Tygerberg Hospitaal (TBH) in die Wes-Kaap Provinsie van Suid-Afrika. Doel: Die studie is uitgevoer om die impak van AI's op hs-CRP en BMI, wat by POC gebruik word, te bepaal vir die voorspelling van terapieverwante newe-effekte onder vetsugtige postmenopousale borskankerpasiënte in Afrika. Metodes: Honderd ses en twintig vroulike BC-pasiënte met kankerstadia wat wissel van 0-III, is tussen Augustus 2014 en Februarie 2017 in die Tygerberg-hospitaal (TBH) in die Wes-Kaap provinsie van Suid-Afrika gewerf vir die studie. 'N Kwasi-eksperimentele studie is uitgevoer. Pasiënte is aanvanklik onderworpe aan KI's en is daarna opgevolg op maande 4, 12 en 24. Basiese kliniese en biomediese assesserings is met die aanvang van die studie uitgevoer om hs-CRP en BMI te voorspel op maande 12 en 24, met behulp van 'n meervoudige toerekening model. 'N ewekansige effekmodel is gebruik om die veranderinge oor tyd te monitor. Statistiese ontledings is uitgevoer met behulp van SPSS 18.0 sagteware (SPSS Inc., Chicago, IL, VSA) en STATA weergawe 16. Ontledings was tweestert en 'n p-waarde <0.05 is as statisties beduidend beskou. Resultate: Die gemiddelde ouderdom van die deelnemers was 61 jaar (SD = 7,11 jaar; 95% BI: 60-62 jaar). Lineêre regressie het aan die lig gebring dat hs-CRP verband hou met middellyfomtrek (OF: 7.5; p = 0. 0116; 95%CI: 1.45 tot 39.61) en BMI (OR: 2.15; p = 0.034, 95%CI: 1.02 tot 4.56) . Tailleomtrek word geassosieer met hipertensie (OR: 3, 83; p = 0.003, 95%CI: 1.56 tot 9.39), en chemoterapie word geassosieer met middellyfomtrek deur (p = 0. 016; 95%CI: 0.11 tot 0. 79 ). hs-CRP-vlakke was beduidend gekorreleer met BMI en totale liggaamsvet (TBF) onder postmenopousale met behulp van aromatase-remmers. Willekeurige modellering van lineêre effekte toon 'n sterker statistiese verband tussen BMI en homosisteïen aan (p = 0,021, 95%CI: 0,0083 tot 0,1029). Gewig en TBF is sterk geassosieer na 24 maande se opvolg. Boonop is hs-CRP geassosieer met BMI (p = 0,0001) en ander inflammatoriese merkers soos kalsium (p = 0,021, 95%CI: 0,0083 tot 0,1029), fosfaat (p = 0,039, 95%BI: 0,0083 tot 0,1029) en ferritien (p = 0,002, 95%BI: 0,0199 tot 0,084). Veelvuldige toerekeningmodellering het aangedui dat daar statisties beduidende variasies in TBF, gewig, homosisteïen, ferritien en kalsium was tussen die basislyn en na 24 maande se opvolging. Wiskundige modellering Vergelyking van genotipering van HyBeacon® sonde tegnologie met Sanger volgordebepaling het getoon dat sensitiwiteit van 99% (95% CI: 94,55 tot 99,97%), spesifisiteit van 89,44% (95% CI: 87,25 tot 91,38%), PPV van 51% opgelewer word (95%: 43,77 tot 58,26%) en NPV van 99,88%(95%CI: 99,31 tot 100,00%). Op grond van die wiskundige model het die aannames aan die lig gebring dat die inkrementele koste-effektiewe verhouding (ICER) R7 044,55 was. Afsluiting: Hierdie studie het aan die lig gebring dat hs-CRP en BMI voorspellers is van CVD-verwante newe-effekte by vetsugtige postmenopousale pasiënte. Kalsium, fosfaat, homosisteïen en ferritien moet ook in POCT opgeneem word. Daar was statisties beduidende variasies in TBF, gewig, hs-CRP, BMI, homosisteïen, ferritien en kalsium tussen basislyn en na 24 maande se opvolg. HyBeacon® sonde tegnologie by POC vir AI-geassosieerde newe-effekte kan in Afrika koste-effektief wees as aanvulling op standaard praktyk. Die geskikte paaie vir die implementering van POC -toetse by postmenopousale borskankeroorlewendes benodig verdere ondersoek in verskillende kliniese omgewings met werklike data vir eksterne validering. | af_ZA |
| dc.description.version | Doctoral | |
| dc.format.extent | xi, 181 pages ; illustrations, includes annexures | |
| dc.identifier.uri | http://hdl.handle.net/10019.1/123642 | |
| dc.language.iso | en_ZA | en_ZA |
| dc.publisher | Stellenbosch : Stellenbosch University | |
| dc.rights.holder | Stellenbosch University | |
| dc.subject | Aromatase -- Inhibitors -- Side effects | en_ZA |
| dc.subject | Point-of-care testing -- Effectiveness | en_ZA |
| dc.subject | Breast cancer -- Women patients | en_ZA |
| dc.subject | Menopause | en_ZA |
| dc.subject | Cardiovascular system -- Diseases -- Risk factors | en_ZA |
| dc.subject | C-reactive protein -- Diagnostic use | en_ZA |
| dc.subject | Obesity | en_ZA |
| dc.subject | UCTD | |
| dc.title | Assessment of point-of-care testing for prediction of aromatase inhibitor-associated side effects in obese postmenopausal breast cancer patients screened for cardiovascular risk factors | en_ZA |
| dc.type | Thesis | en_ZA |