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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT00897702

Enrollment

269

Registered

2009-05-12

Start date

2007-01-09

Completion date

2026-01-23

Last updated

2026-01-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer

Keywords

recurrent breast cancer, male breast cancer, stage IV breast cancer

Brief summary

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.

Interventions

OTHERBlood 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.

OTHERimmunoenzyme technique

PROCEDUREbiopsy

PROCEDUREhistopathologic examination

Study design

Observational model

CASE_ONLY

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Healthy volunteers

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

Design outcomes

Primary

Measure	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

Measure	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

Countries

United States

Contacts

STUDY_CHAIRSarat Chandarlapaty, MD, PhD

Memorial Sloan Kettering Cancer Center

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026