Molecular Mechanisms of Clinical Resistance to Targeted Therapy Among Patients With Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to learn why certain drugs stop working in patients.In lab studies, tumors become resistant in several ways. Specific molecules seem to change and this may be why therapy stops working. However, we do not know if the same molecules change in patients. This study is being done to see if they do change. If we learn more about how patients become resistant, we may be able to offer better treatment in the future.

Official Title
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Molecular Mechanisms of Clinical Resistance to Targeted Therapy Among Patients With Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Other: Blood draw
* Other: immunoenzyme technique
* Procedure: biopsy
* Procedure: histopathologic examination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients: Diagnosed with breast cancer. Patient must be able to consent to a biopsy Patient must be able to safely undergo a secondary biopsy, if needed. Cohort 1 Patients who previously received treatment with anti-HER2 therapy (including trastuzumab, pertuzumab, TDM1, lapatinib, neratibin, or DS8201) as part of adjuvant chemotherapy and now have progressive or recurrent breast cancer or, patients who previously (or currently) received anti-HER2 therapy as part of a regimen for metastatic breast cancer and subsequently experienced. Evidence of disease progression or recurrence after prior therapy (e.g. radiologic progression by RECIST criteria or new metastasis). Prior tumor biopsy (may be original) defined as HER2+ by amplification by FISH (>1.9 gene copy number) or IHC 3+. Cohort 2 Patients who previously received treatment with hormonal therapy (including aromatase inhibitors or SERMs or SERDs) as a part of adjuvant therapy and now have progressive or recurrent breast cancer or patients who previously (or currently) receive hormonal therapy as part of a regimen for metastatic breast cancer and subsequently experienced evidence of disease progression. Cohort 3 Patients not eligible for Cohorts 1 or 2. Exclusion Criteria: Patients who are unable to consent to a biopsy. Patients for whom a repeat biopsy would be medically unsafe
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Blood draw|A single 10ml tube of blood will also be obtained for a comparison of patient's normal DNA for genomic analyses either at the time of the procedure or at a followup appointment if feasible.|
|Other: immunoenzyme technique|nan|
|Procedure: biopsy|nan|
|Procedure: histopathologic examination|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To look for mutations in druggable oncogenic pathways in tumors progressing on anti-HER2 therapy or hormonal therapy |  | 3 years | 
| To characterize the activity of the PI3K signaling pathway in progressive breast tumors using proteomic methods |  | 3 years | 
| To develop new laboratory models of treatment refractory breast cancer from human tumor specimens |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To look for mutations in druggable oncogenic pathways in tumor progressing on breast cancer targeted therapies |  | 3 years | 
| To evaluate dynamic proteomic changes in response to inhibition of the RTK/PI3K/ATK/mTOR pathway. |  | 3 years | 
| To characterize the genetic heterogeneity of progressive, metastatic tumors using next generation sequencing |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent breast cancer, male breast cancer, stage IV breast cancer