MIRNA Profiling of Breast Cancer in Patients Undergoing Neoadjuvant or Adjuvant Treatment for Locally Advanced & Inflammatory Breast Cancer
| Status: | Recruiting |
|---|---|
| Conditions: | Breast Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 6/6/2018 |
| Start Date: | November 2009 |
| End Date: | April 2019 |
| Contact: | George Somlo, MD |
| Email: | gsomlo@coh.org |
| Phone: | 800 826-4673 |
MicroRNAs (MiRNAs) regulate the translation of RNAs and are implicated in cell proliferation
and renewal both under physiologically normal as well as in malignant conditions.
Dysregulation of specific miRNAs may be associated with either gaining oncogenic or loosing
tumor suppressing functions. MiRNA dysregulation has been implicated in breast cancer
tumorigenic (stem cell) and non-tumorigenic development. Therefore, miRNA profiling of
treatment naïve and treatment-exposed breast tumors and sequential samples of blood/serum
will allow for identification of miRNA markers of prognosis and as indicators and potential
targets for personalized therapies. In this proposal, specimens from patients treated in the
clinical breast cancer program on already existing protocols (IRB 05091 and 05015) will be
characterized by Dr. Rossi's laboratory and collaborators, and the information gained will be
applied to develop specific therapies.
and renewal both under physiologically normal as well as in malignant conditions.
Dysregulation of specific miRNAs may be associated with either gaining oncogenic or loosing
tumor suppressing functions. MiRNA dysregulation has been implicated in breast cancer
tumorigenic (stem cell) and non-tumorigenic development. Therefore, miRNA profiling of
treatment naïve and treatment-exposed breast tumors and sequential samples of blood/serum
will allow for identification of miRNA markers of prognosis and as indicators and potential
targets for personalized therapies. In this proposal, specimens from patients treated in the
clinical breast cancer program on already existing protocols (IRB 05091 and 05015) will be
characterized by Dr. Rossi's laboratory and collaborators, and the information gained will be
applied to develop specific therapies.
Current neoadjuvant or adjuvant treatment strategies do not allow for rationale incorporation
of such agents. One needs tools to predict both de novo and acquired resistance to
therapeutic agents. This is a difficult task, due to the compound nature of escape routes:
tumor exposure is usually to a combination of therapeutic agents and the mechanisms of
resistance are broad: intrinsic resistance due to existing mutations, or regulatory - miRNA,
other epigenetic - alterations, polymorphisms, tumor cell adaptation via new mutations and
activation of alternative pathways, lack of optimal pharmacokinetics/genomics, activation of
efflux mechanisms, accelerated repair mechanisms are involved.
Similarly, not all patients who are candidates for primary surgical intervention to be
followed by post-operative adjuvant therapy benefit from such systemic treatments. The
mechanisms of resistance be it de novo in surviving stem cell/tumorigenic components, or
acquired by cells left behind "dormant" after the surgical intervention, are not well
delineated.
Breast tumors subjected to neoadjuvant chemotherapy allow for baseline and treatment-effected
sampling. Characterization of core biopsy specimens of primary tumors procured prior to
exposure to neoadjuvant therapy from different varieties of breast cancer subtypes, and of
subsequent mid-treatment and intraoperative (procured during definitive surgery following
completion of neoadjuvant therapy) samples should help to assess the predictive value of the
pre-treatment and post-treatment miRNA expression profile for complete and near complete
response, as a surrogate marker for survival. Similarly, patterns of de novo and acquired
resistance may emerge when assessment of pre- and post treatment miRNA expression profiles
are analyzed in a supervised manner of classification using pathological response as
classifier. Samples obtained from patients with primary surgical removal of their tumors
before any systemic treatment exposure on the other hand, will allow for determining markers
of prognosis, and predictors for response to therapeutic targeting agents.
Time Perspective: Retrospective/Prospective
of such agents. One needs tools to predict both de novo and acquired resistance to
therapeutic agents. This is a difficult task, due to the compound nature of escape routes:
tumor exposure is usually to a combination of therapeutic agents and the mechanisms of
resistance are broad: intrinsic resistance due to existing mutations, or regulatory - miRNA,
other epigenetic - alterations, polymorphisms, tumor cell adaptation via new mutations and
activation of alternative pathways, lack of optimal pharmacokinetics/genomics, activation of
efflux mechanisms, accelerated repair mechanisms are involved.
Similarly, not all patients who are candidates for primary surgical intervention to be
followed by post-operative adjuvant therapy benefit from such systemic treatments. The
mechanisms of resistance be it de novo in surviving stem cell/tumorigenic components, or
acquired by cells left behind "dormant" after the surgical intervention, are not well
delineated.
Breast tumors subjected to neoadjuvant chemotherapy allow for baseline and treatment-effected
sampling. Characterization of core biopsy specimens of primary tumors procured prior to
exposure to neoadjuvant therapy from different varieties of breast cancer subtypes, and of
subsequent mid-treatment and intraoperative (procured during definitive surgery following
completion of neoadjuvant therapy) samples should help to assess the predictive value of the
pre-treatment and post-treatment miRNA expression profile for complete and near complete
response, as a surrogate marker for survival. Similarly, patterns of de novo and acquired
resistance may emerge when assessment of pre- and post treatment miRNA expression profiles
are analyzed in a supervised manner of classification using pathological response as
classifier. Samples obtained from patients with primary surgical removal of their tumors
before any systemic treatment exposure on the other hand, will allow for determining markers
of prognosis, and predictors for response to therapeutic targeting agents.
Time Perspective: Retrospective/Prospective
Inclusion Criteria:
- Female,
- Breast Cancer
- > 18 years,
- regardless of histology, treatment phase, or stage
Exclusion Criteria:
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