Epigenetic Testing for Breast Cancer Risk Stratification
Promoter region hypermethylation of tumor suppressor genes is one the earliest molecular events in malignant transformation and is readily detectable in apparently normal benign breast epithelium adjacent to breast cancers. The investigators hypothesize that DNA methylation of certain genes occurs as a field change in benign breast tissue that is at high risk for malignant transformation, and as such, can be exploited for tissue-based breast cancer risk stratification. Additional work is required to identify new DNA methylation markers potentially useful for periareolar fine needle aspiration (RP-FNA)-based breast cancer risk stratification, to determine whether these markers are methylated more frequently in benign samples from women who develop breast cancer, to determine whether assessment of these markers is reproducible, to determine whether tamoxifen reduces DNA methylation, and to better understand the pattern of DNA methylation in benign samples from unselected healthy control populations. Each of these objectives contributes to advancement of a clinically useful RP-FNA-based breast cancer risk stratification test.
In addition, identification of genes that are preferentially methylated in estrogen receptor (ER) negative breast cancer will provide clues to the underlying biology responsible for this aggressive form of breast cancer. This knowledge may lead to the discovery of the causes of ER negative breast cancer, approaches for recognizing women at increased risk for this type of breast cancer, and approaches for reducing this risk.
This study seeks to identify patterns of DNA methylation in benign breast epithelial cells associated with an increased risk for breast cancer with a focus on ER negative breast cancer.
研究概览
地位
条件
详细说明
Promoter region hypermethylation of tumor suppressor genes is one the earliest molecular events in malignant transformation and is readily detectable in apparently normal benign breast epithelium adjacent to breast cancers. We hypothesize that DNA methylation of certain genes occurs as a field change in benign breast tissue that is at high risk for malignant transformation, and as such, can be exploited for tissue-based breast cancer risk stratification. Additional work is required to identify new DNA methylation markers potentially useful for periareolar fine needle aspiration (RP-FNA)-based breast cancer risk stratification, to determine whether these markers are methylated more frequently in benign samples from women who develop breast cancer, to determine whether assessment of these markers is reproducible, to determine whether tamoxifen reduces DNA methylation, and to better understand the pattern of DNA methylation in benign samples from unselected healthy control populations. Each of these objectives contributes to advancement of a clinically useful RP-FNA-based breast cancer risk stratification test.
In addition, identification of genes that are preferentially methylated in estrogen receptor (ER) negative breast cancer will provide clues to the underlying biology responsible for this aggressive form of breast cancer. This knowledge may lead to the discovery of the causes of ER negative breast cancer, approaches for recognizing women at increased risk for this type of breast cancer, and approaches for reducing this risk.
研究类型
注册 (实际的)
联系人和位置
学习地点
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Texas
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Dallas、Texas、美国、75204
- UT Southwestern Medical Center
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
描述
Inclusion Criteria:
- Women between the ages of 30 and 79.
- Untreated stage 1 - 3 invasive breast cancer or a woman never diagnosed with breast cancer.
- BI-RADS 1, 2, or 3 breast imaging within 12 months for women >40 years of age recruited into the control group.
Exclusion Criteria:
- <30 or >80 years of age
- Unable to provide informed consent
- Presence of an undefined palpable or mammographic breast lesion suspicious for malignancy (BIRADS 4 or 5)
- Breast implants
- Bilateral prophylactic mastectomy
- Any prior breasts irradiation
- Any systemic chemotherapy in the past
- Performance status that restricted normal activity for a significant portion of the day
- Use of luteinizing-hormone-releasing-hormone (LHRH) analogs, prolactin inhibitors, antiandrogens, or systemic glucocorticoids within three months
- Ever use of tamoxifen, raloxifene, or other SERMs
- Ever use of aromatase inhibitors
- Pregnancy or lactation within six months
Bleeding diathesis of any kind
- Inherited coagulation disorder
- Current coumadin use
- Use of drugs that inhibit platelet aggregation within 10 days
学习计划
研究是如何设计的?
设计细节
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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DNA methylation
大体时间:2 years
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This objective assesses methylation of seven genes in 97 archival breast cancer samples.
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2 years
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Frequency of methylation
大体时间:2 years
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Measure the frequency of methylation of ER positive and ER negative breast cancer-associated genes in benign breast epithelial cells obtained by RP-FNA.
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2 years
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合作者和调查者
调查人员
- 首席研究员:Rolf Brekken, MD、UT Southwetstern Medical Center
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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