Clinical trial NCT00353483: Effect of Neoadjuvant or Adjuvant Systemic Therapy on Breast Cancers, Bone Marrow Cancer Cells, and Circulating Cancer Cells
Official title: Effect of Neoadjuvant or Adjuvant Systemic Therapy on Breast Cancers, Bone Marrow Cancer Cells, and Circulating Cancer Cells
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Breast Neoplasms
Keywords: Breast Cancer
Neoadjuvant
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2006-07-18
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients seen in clinic at Washington University School of Medicine.

Brief summary: The main purpose of this study is to compare genetic markers present on tumor cells before and after chemotherapy.

Detailed description: In this study, the investigators propose that persistent disseminated tumor cells (DTC) present after systemic therapy represent a unique subpopulation of all DTC, are predictors of a poor response to systemic therapy and correlate with poor clinical outcome. The investigators hypothesize that systemic therapy-resistant DTC can be identified by their expression of a unique constellation of tumor marker proteins which may be similar to those expressed by breast cancer stem cells. In this research, the investigators' specific aims are : 1) to characterize tumor markers expressed by DTC which are present after systemic therapy, 2) to compare the expression of these markers to that on DTC detected prior to systemic therapy, 3) to correlate expression of the defined tumor markers on DTC with clinical outcome of breast cancer patients to identify those markers that are predictive of disease recurrence, 4) to utilize biomarkers identified in Specific Aims 1 and 2 to isolate purified DTC for further molecular analysis.

Eligibility criteria: Inclusion Criteria:

* Recently diagnosed with clinical stage II, III, or IV breast cancer
* Planning to undergo neoadjuvant or adjuvant systemic therapy; patients who have already completed neoadjuvant systemic therapy are also eligible
* Must be \>= 18 years of age
* If female, must not be pregnant
* Must not have Hepatitis B, C, or HIV
* Must be willing and able to sign informed consent document

Primary outcomes:
measure: Characterize tumor markers expressed by DTC which are present after systemic therapy
timeFrame: Approximately 6 years
measure: Compare the expression of these markers to that on DTC detected prior to systemic therapy
timeFrame: Approximately 6 years
measure: Correlate expression of the defined tumor markers on DTC with clinical outcome of breast cancer patients to identify those markers that are predictive of disease recurrence.
timeFrame: Approximately 6 years
measure: Compare the tumor markers present on DTC before and after chemotherapy with the tumor marker expression of the primary tumor and post-treatment tumor.
timeFrame: Approximately 6 years.
measure: To xenograft tumor cells into mice for further genetic and phenotypic characterization.
timeFrame: Approximately 6 years
Secondary outcomes:
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Rebecca Aft, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Diel IJ, Cote RJ. Bone marrow and lymph node assessment for minimal residual disease in patients with breast cancer. Cancer Treat Rev. 2000 Feb;26(1):53-65. doi: 10.1053/ctrv.1999.0150.
citation: Braun S, Pantel K, Muller P, Janni W, Hepp F, Kentenich CR, Gastroph S, Wischnik A, Dimpfl T, Kindermann G, Riethmuller G, Schlimok G. Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer. N Engl J Med. 2000 Feb 24;342(8):525-33. doi: 10.1056/NEJM200002243420801.
citation: Braun S, Naume B. Circulating and disseminated tumor cells. J Clin Oncol. 2005 Mar 10;23(8):1623-6. doi: 10.1200/JCO.2005.10.073. No abstract available.
citation: Janni W, Rack B, Schindlbeck C, Strobl B, Rjosk D, Braun S, Sommer H, Pantel K, Gerber B, Friese K. The persistence of isolated tumor cells in bone marrow from patients with breast carcinoma predicts an increased risk for recurrence. Cancer. 2005 Mar 1;103(5):884-91. doi: 10.1002/cncr.20834.
citation: Klein CA, Blankenstein TJ, Schmidt-Kittler O, Petronio M, Polzer B, Stoecklein NH, Riethmuller G. Genetic heterogeneity of single disseminated tumour cells in minimal residual cancer. Lancet. 2002 Aug 31;360(9334):683-9. doi: 10.1016/S0140-6736(02)09838-0.
citation: Choesmel V, Pierga JY, Nos C, Vincent-Salomon A, Sigal-Zafrani B, Thiery JP, Blin N. Enrichment methods to detect bone marrow micrometastases in breast carcinoma patients: clinical relevance. Breast Cancer Res. 2004;6(5):R556-70. doi: 10.1186/bcr898. Epub 2004 Jul 29.
citation: Lesurf R, Griffith OL, Griffith M, Hundal J, Trani L, Watson MA, Aft R, Ellis MJ, Ota D, Suman VJ, Meric-Bernstam F, Leitch AM, Boughey JC, Unzeitig G, Buzdar AU, Hunt KK, Mardis ER. Genomic characterization of HER2-positive breast cancer and response to neoadjuvant trastuzumab and chemotherapy-results from the ACOSOG Z1041 (Alliance) trial. Ann Oncol. 2017 May 1;28(5):1070-1077. doi: 10.1093/annonc/mdx048.