Determinants of transdermal drug delivery to the normal and the radiated breast

正常乳房和放射乳房经皮药物输送的决定因素

基本信息

  • 批准号:
    10093981
  • 负责人:
  • 金额:
    $ 36.17万
  • 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:
    2019-02-05 至 2024-01-31
  • 项目状态:
    已结题

项目摘要

Duct carcinoma in situ (DCIS) of the breast comprises about 20% of new breast malignancies in screened populations. Treatment consists of breast conserving surgery (BCS) in about 75% of women, usually followed by (RT), which halves the risk of new cancer events on the same side. Oral endocrine therapy (OET) further reduces the risk to the same breast by 1/3rd , and cuts the risk to the other breast by one-half. However, OET is declined by more than half of DCIS patients, given its thromboembolic and uterine risks (selective estrogen receptor modulators), and musculoskeletal effects (aromatase inhibitors). Drug delivery methods that avoid the adverse effects of these agents will represent a significant advance. Transdermal delivery is a well-recognized and effective alternative. Advantages include low systemic exposure, longer retention in the local tissue, and avoidance of first-pass hepatic metabolism. Encouraging preliminary data on local transdermal therapy (LTT) with 4-hydroxytamoxifen (4-OHT) applied to the breast skin have led us to conduct clinical trials aimed at establishing the equivalence of transdermal and oral treatment of the breast. If successful, this will be a novel and potentially transformative development for the DCIS population, and for women at high risk for breast cancer. However, there are significant knowledge gaps regarding the causes of individual variations in dermal permeation. And current studies exclude women who have undergone breast RT because this may alter dermal permeation and/or distribution through the breast. Since DCIS patients who receive RT breast derive additional protection for both breasts through the use of OET, an evaluation of drug permeation through radiated skin is important. The Aims of our study are 1) to identify the skin features that drive inter-individual variation in dermal drug permeation between individuals, and 2) to assess the feasibility of transdermal drug delivery to the radiated breast. We will do this by enrolling breast cancer survivors who have one radiated and one intact, non- radiated breast, and are willing to apply 4-OHT gel to both breasts for a period of 3-5 weeks. We will then obtain skin punch and core needle biopsies of both breasts, measure drug concentration in the breast tissue cores, and assess individual characteristics (breast size, adiposity) and skin features (thickness of skin layers, gene and protein expression) that may explain the inter-individual variation in drug concentration. In Aim 1, these features will be used to develop a predictive model that identifies the important determinants of dermal drug delivery in the unradiated breast. In Aim 2, skin features will be compared between the radiated and unradiated breast, to determine differences introduced by radiation that are important for dermal permeation. Drug concentrations will be compared between the radiated and unradiated breast. At the end, we will answer two questions regarding which little information exists currently: 1) which women are good candidates for transdermal therapy? 2) Will transdermal delivery work for the radiated breast?
乳腺导管原位癌(DCIS)约占新发乳腺恶性肿瘤的20%

项目成果

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SEEMA Ahsan KHAN其他文献

SEEMA Ahsan KHAN的其他文献

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{{ truncateString('SEEMA Ahsan KHAN', 18)}}的其他基金

Surgical Multispecialty Access to Research in Residency Training (SMART)
外科多专科住院医师培训研究 (SMART)
  • 批准号:
    10333342
  • 财政年份:
    2021
  • 资助金额:
    $ 36.17万
  • 项目类别:
Surgical Multispecialty Access to Research in Residency Training (SMART)
外科多专科住院医师培训研究 (SMART)
  • 批准号:
    10565893
  • 财政年份:
    2021
  • 资助金额:
    $ 36.17万
  • 项目类别:
Determinants of transdermal drug delivery to the normal and the radiated breast
正常乳房和放射乳房经皮药物输送的决定因素
  • 批准号:
    10559716
  • 财政年份:
    2019
  • 资助金额:
    $ 36.17万
  • 项目类别:
Determinants of transdermal drug delivery to the normal and the radiated breast
正常乳房和放射乳房经皮药物输送的决定因素
  • 批准号:
    10334490
  • 财政年份:
    2019
  • 资助金额:
    $ 36.17万
  • 项目类别:
Northwestern Cancer Prevention Consortium
西北癌症预防联盟
  • 批准号:
    10686120
  • 财政年份:
    2019
  • 资助金额:
    $ 36.17万
  • 项目类别:
Northwestern Cancer Prevention Consortium
西北癌症预防联盟
  • 批准号:
    10250326
  • 财政年份:
    2019
  • 资助金额:
    $ 36.17万
  • 项目类别:
Northwestern Cancer Prevention Consortium
西北癌症预防联盟
  • 批准号:
    10006889
  • 财政年份:
    2019
  • 资助金额:
    $ 36.17万
  • 项目类别:
Northwestern Cancer Prevention Consortium
西北癌症预防联盟
  • 批准号:
    10473768
  • 财政年份:
    2019
  • 资助金额:
    $ 36.17万
  • 项目类别:
Progesterone Signaling and Blockade in Human Breast Tumorigenesis and Prevention
人类乳腺肿瘤发生和预防中的黄体酮信号传导和阻断
  • 批准号:
    9315776
  • 财政年份:
    2015
  • 资助金额:
    $ 36.17万
  • 项目类别:
Nipple Fluid Hormone Levels and Breast Cancer Risk
乳头液激素水平与乳腺癌风险
  • 批准号:
    7825331
  • 财政年份:
    2007
  • 资助金额:
    $ 36.17万
  • 项目类别:

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Resistance to paclitaxel in triple negative breast cancer cells is associated with ABCB1 gene rearrangement
三阴性乳腺癌细胞对紫杉醇的耐药性与 ABCB1 基因重排有关
  • 批准号:
    315555
  • 财政年份:
    2014
  • 资助金额:
    $ 36.17万
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