The Importance of Nonpharmacogenetic Factors in Endocrine Therapy

McCowan, Colin; Thompson, Alastair

doi:10.2217/pgs.12.29

Cited by 12 publications

(11 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Over half of the women, whose notes were reviewed, reported side effects due to endocrine therapy with differences by whether women were taking tamoxifen or AIs, which is reported elsewhere (McCowan and Thompson, 2012). …”

Section: Discussionmentioning

confidence: 91%

Cohort study of adherence to adjuvant endocrine therapy, breast cancer recurrence and mortality

et al. 2013

View full text Add to dashboard Cite

Background:Adjuvant endocrine therapy is recommended for women with oestrogen receptor-positive breast cancer, but many women do not take the medication as directed and they stop treatment before completing the standard 5-year duration.Methods:This retrospective cohort study conducted between 1993 and 2008 of all women with incident breast cancer, who are residing in the Tayside region of Scotland, examined adherence to prescribed adjuvant tamoxifen or aromatase inhibitors (AIs). Survival analysis examined the effect of adherence on all-cause mortality, breast cancer death and recurrence, using linked prescribing, cancer registry, clinical cancer audit, hospital discharge and death records.Results:A total of 3361 women with breast cancer were followed for a median 4.47 years (interquartile range (IQR)=2.04–8.55). The median overall adherence was 90% (IQR=90–100%), but the annual adherence reduced after a longer period from diagnosis. Low adherence of <80% was associated with poorer survival (hazard ratios=1.20; 95% confidence interval=1.03–1.40, P=0.019). There was no significant difference for low adherence over the treatment period and recurrence, or breast cancer death, but patients with high annual adherence for 5 years had better outcomes than those with 3 or less.Conclusion:Low adherence to all adjuvant endocrine therapy for women with breast cancer, whether tamoxifen or AI, increases the risk of death.

show abstract

Section: Discussionmentioning

confidence: 91%

Cohort study of adherence to adjuvant endocrine therapy, breast cancer recurrence and mortality

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Menopausal side effects may be attributed to tamoxifen therapy (particularly hot flushes), which may in turn lead to prescriptions for drugs aimed at relief of these symptoms (86). Selective serotonin reuptake inhibitors are sometimes used to treat the side effects of tamoxifen and inhibit the activity of the CYP2D6 enzyme to varying degrees (20,(87)(88)(89).…”

Section: Implications For Clinical Practicementioning

confidence: 99%

Cytochrome P-450 2D6 (CYP2D6) Genotype and Breast Cancer Recurrence in Tamoxifen-Treated Patients: Evaluating the Importance of Loss of Heterozygosity

Ahern¹,

Hertz²,

Damkier³

et al. 2016

Am. J. Epidemiol.

View full text Add to dashboard Cite

Tamoxifen therapy for estrogen receptor-positive breast cancer reduces the risk of recurrence by approximately one-half. Cytochrome P-450 2D6, encoded by the polymorphic cytochrome P-450 2D6 gene (CYP2D6), oxidizes tamoxifen to its most active metabolites. Steady-state concentrations of endoxifen (4-hydroxy-Ndesmethyltamoxifen), the most potent antiestrogenic metabolite, are reduced in women whose CYP2D6 genotypes confer poor enzyme function. Thirty-one studies of the association of CYP2D6 genotype with breast cancer survival have yielded heterogeneous results. Some influential studies genotyped DNA from tumorinfiltrated tissues, and their results may have been susceptible to germline genotype misclassification from loss of heterozygosity at the CYP2D6 locus. We systematically reviewed 6 studies of concordance between genotypes obtained from paired nonneoplastic and breast tumor-infiltrated tissues, all of which showed excellent CYP2D6 genotype agreement. We applied these concordance data to a quantitative bias analysis of the subset of the 31 studies that were based on genotypes from tumor-infiltrated tissue to examine whether genotyping errors substantially biased estimates of association. The bias analysis showed negligible bias by discordant genotypes. Summary estimates of association, with or without bias adjustment, indicated no clinically important association between CYP2D6 genotype and breast cancer survival in tamoxifen-treated women. breast neoplasms; cytochrome P-450 2D6; tamoxifen Abbreviations: ATAC, Arimidex, Tamoxifen, Alone or in Combination; BIG 1-98, Breast International Group 1-98; CI, confidence interval; CYP2D6, cytochrome P-450 2D6; FFPE, formalin-fixed, paraffin-embedded; FFPE-T, formalin-fixed, paraffinembedded tumor tissue; FFPE-TN, formalin-fixed, paraffin-embedded tumor tissue with nonneoplastic tissue; HWE, HardyWeinberg equilibrium; LOH, loss of heterozygosity; RR, relative risk.

show abstract

“…[7][8][9] Suboptimal fetal growth is important as SGA babies comprise 28-45% of nonanomalous stillbirths. 10,11 Placental insufficiency is a major contributor to the pathophysiology in SGA pregnancies and contributes to the adverse perinatal outcomes. 12 Infants born SGA have higher rates of neurodevelopmental delay, poor school performance, childhood and adult obesity, as well as metabolic disease.…”

Section: Introductionmentioning

confidence: 99%

Evidence-based national guidelines for the management of suspected fetal growth restriction: comparison, consensus, and controversy

McCowan

Figueras

Anderson

2018

American Journal of Obstetrics and Gynecology

332

325

View full text Add to dashboard Cite

Small for gestational age is usually defined as an infant with a birthweight <10th centile for a population or customized standard. Fetal growth restriction refers to a fetus that has failed to reach its biological growth potential because of placental dysfunction. Small-for-gestational-age babies make up 28-45% of nonanomalous stillbirths, and have a higher chance of neurodevelopmental delay, childhood and adult obesity, and metabolic disease. The majority of small-for-gestational-age babies are not recognized before birth. Improved identification, accompanied by surveillance and timely delivery, is associated with reduction in small-for-gestational-age stillbirths. Internationally and regionally, detection of small for gestational age and management of fetal growth problems vary considerably. The aim of this review is to: summarize areas of consensus and controversy between recently published national guidelines on small for gestational age or fetal growth restriction; highlight any recent evidence that should be incorporated into existing guidelines; and identify future research priorities in this field. A search of MEDLINE, Google, and the International Guideline Library identified 6 national guidelines on management of pregnancies complicated by fetal growth restriction/small for gestational age published from 2010 onwards. There is general consensus between guidelines (at least 4 of 6 guidelines in agreement) in early pregnancy risk selection, and use of low-dose aspirin for women with major risk factors for placental insufficiency. All highlight the importance of smoking cessation to prevent small for gestational age. While there is consensus in recommending fundal height measurement in the third trimester, 3 specify the use of a customized growth chart, while 2 recommend McDonald rule. Routine third-trimester scanning is not recommended for small-for-gestational-age screening, while women with major risk factors should have serial scanning in the third trimester. Umbilical artery Doppler studies in suspected small-for-gestational-age pregnancies are universally advised, however there is inconsistency in the recommended frequency for growth scans after diagnosis of small for gestational age/fetal growth restriction (2-4 weekly). In late-onset fetal growth restriction (≥32 weeks) general consensus is to use cerebral Doppler studies to influence surveillance and/or delivery timing. Fetal surveillance methods (most recommend cardiotocography) and recommended timing of delivery vary. There is universal agreement on the use of corticosteroids before birth at <34 weeks, and general consensus on the use of magnesium sulfate for neuroprotection in early-onset fetal growth restriction (<32 weeks). Most guidelines advise using cardiotocography surveillance to plan delivery in fetal growth restriction <32 weeks. The recommended gestation at delivery for fetal growth restriction with absent and reversed end-diastolic velocity varies from 32 to ≥34 weeks and 30 to ≥34 weeks, respectively. Overall, where there is high-q...

show abstract

The Importance of Nonpharmacogenetic Factors in Endocrine Therapy

Cited by 12 publications

References 102 publications

Cohort study of adherence to adjuvant endocrine therapy, breast cancer recurrence and mortality

Cohort study of adherence to adjuvant endocrine therapy, breast cancer recurrence and mortality

Cytochrome P-450 2D6 (CYP2D6) Genotype and Breast Cancer Recurrence in Tamoxifen-Treated Patients: Evaluating the Importance of Loss of Heterozygosity

Evidence-based national guidelines for the management of suspected fetal growth restriction: comparison, consensus, and controversy

Contact Info

Product

Resources

About