Biologic and Patient Variation Affecting Breast Cancer Treatment Efficacy
影响乳腺癌治疗效果的生物学和患者变异
基本信息
- 批准号:9760646
- 负责人:
- 金额:$ 4.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-05-08 至 2021-05-07
- 项目状态:已结题
- 来源:
- 关键词:AccountingAddressAdherenceAdjuvantAdjuvant TherapyAffectAgeAromatase InhibitorsBehavioralBiologicalBiological AssayBiological MarkersBreast Cancer EpidemiologyBreast Cancer PatientBreast Cancer PreventionBreast Cancer Risk FactorBreast Cancer TreatmentBreast Cancer survivorBreast CarcinomaCancer Cell GrowthCharacteristicsClinical TrialsDataData QualityDenmarkDiagnosisDiseaseDrug resistanceEffectivenessEnzymesEstradiolEstrogen MetabolismEstrogen Receptor alphaEstrogen receptor positiveEstrogensEstroneExposure toGoalsGuidelinesHealthcareHydroxysteroid DehydrogenasesIndividualLeadMalignant NeoplasmsMeasuresMetabolic PathwayMethodologyMolecularNaturePathway interactionsPatient-Focused OutcomesPatientsPharmacoepidemiologyPopulationPopulation-Based RegistryPremenopausePrognostic MarkerProtocols documentationRadiation therapyRecurrenceRegistriesResearch Project GrantsResearch ProposalsResistanceResourcesRiskSamplingSkin CarcinomaSurvival RateSystemTamoxifenTherapeuticTimeTime trendTrastuzumabTreatment EfficacyTumor BiologyTumor MarkersVariantWomanalternative treatmentanalytical methodbasebiomarker-drivenbreast cancer diagnosiscancer recurrencechemotherapycohortcompliance behaviorepidemiology studyfollow-uphigh riskhormone therapyimprovedimproved outcomeinsightinterestmalignant breast neoplasmmortalityneoplasm registrynew therapeutic targetoutcome forecastpatient variabilitypopulation basedprecision medicinepredictive markerpreventsocialsurvivorshiptherapeutic targettime usetreatment durationtrendtumortumor growth
项目摘要
Aside from non-melanoma skin cancer, breast carcinoma is the most commonly diagnosed malignancy among
women, with approximately 1.7 million new diagnoses annually worldwide. Over the past decades there have
been substantial improvements in the 5-year survival rates for women diagnosed with breast cancer, however
the long-term risk of breast cancer recurrence remains high (20–40% over approximately 20 years). There is a
dearth of information regarding the epidemiology of breast cancer recurrence, and a need to identify modifiable
patient and tumor characteristics that affect the risk of breast cancer recurrence. Premenopausal women
diagnosed with estrogen receptor positive breast cancer are prescribed tamoxifen for up to ten years to prevent
breast cancer recurrence. Previous studies suggest that patient adherence is low, yet the impact among
premenopausal women has not yet been evaluated. Resistance to tamoxifen therapy may arise from increased
intratumoral expression of estrogen-related metabolites. Biomarkers that are predictive of tamoxifen resistance
would identify patients amenable to additional therapies to prevent recurrence. The overarching goal of this
research proposal is to evaluate biomarkers, patient characteristics, and treatment-related factors that help
explain the variation in effectiveness of adjuvant endocrine therapy in preventing breast cancer recurrence. To
address this goal, this project will leverage resources from the Danish healthcare registry system, which includes
nearly complete high-quality data with information on breast cancer recurrence. Aim 1a will describe the trends
in breast cancer recurrence over the past 35 years and aim 1b will estimate the population-level effect of the
introduction of three biomarker-driven adjuvant therapies—tamoxifen, aromatase inhibitors, and trastuzumab—
on breast cancer recurrence risk using summary level data from the Danish Cancer Registry. These aims will
describe the trends in breast cancer recurrence over time, using Poisson regression and will estimate the
population-level causal effect of the introductions of tamoxifen, aromatase inhibitors, and trastuzumab as well
as any major changes in guidelines to the indication for each adjuvant therapy. This aim will use the newly
developed trend-in-trend analytic method to estimate the population-level impact of the introduction of each
adjuvant therapy. Aim 2 will investigate the impact of adherence to endocrine therapy on breast cancer
recurrence in an exclusively premenopausal cohort. Aim 3 will evaluate the effect of two enzymes, 17β-
hydroxysteroid dehydrogenase 1 and 2, that regulate the intratumoral concentration of estrogen-related
metabolites as markers of tamoxifen resistance in an exclusively premenopausal cohort. The results from this
proposed research project will provide insight into the epidemiology of breast cancer recurrence. Furthermore, it
will lead to improved understanding of the effect of patient adherence to adjuvant endocrine therapy on the risk
of recurrence as well as the contribution of intratumoral concentrations of estrogen-related metabolites on
tamoxifen resistance, which may lead to identification of new therapeutic targets.
除了非黑色素瘤皮肤癌,乳腺癌是最常见的恶性肿瘤
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Lindsay Jane Collin其他文献
Lindsay Jane Collin的其他文献
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{{ truncateString('Lindsay Jane Collin', 18)}}的其他基金
Identifying factors associated with ovarian cancer recurrence using a population-based approach
使用基于人群的方法识别与卵巢癌复发相关的因素
- 批准号:
10581186 - 财政年份:2023
- 资助金额:
$ 4.5万 - 项目类别:
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