Biomarkers in Tissue Samples From Patients With Newly Diagnosed Breast Cancer Treated With Zoledronic Acid

Not Applicable

Terminated

Conditions: Estrogen Receptor-positive Breast Cancer
Invasive Ductal Breast Carcinoma
Stage IB Breast Cancer
Stage IIB Breast Cancer
Progesterone Receptor-positive Breast Cancer
Stage IIA Breast Cancer
Stage IA Breast Cancer

Interventions: Drug: zoledronic acid
Other: laboratory biomarker analysis
Procedure: therapeutic conventional surgery

Registration Number: NCT01409811

Lead Sponsor: City of Hope Medical Center

Brief Summary: This pilot clinical trial studies biomarkers in tissue samples from patients with newly diagnosed breast cancer treated with zoledronic acid (ZA). Studying samples of tumor tissue in the laboratory from patients receiving ZA may help doctors learn more about the effects of ZA on cells. It may also help doctors understand how well patients respond to treatment.

Detailed Description: PRIMARY OBJECTIVES:

I. To evaluate 14 tumor biomarkers of growth and metastasis (10 by microarray and 4 by RT-PCR) for change in response to ZA.

SECONDARY OBJECTIVES:

I. To evaluate 30 measures of immunologic function (by Luminex panel) for change in response to ZA a) after 48-72 hours and b) after 10-23 days.

II. To explore additional tumors biomarkers (approximately 20 by immunohistochemistry) for change in response to ZA.

OUTLINE: Patients receive zoledronic acid intravenously (IV) over 15 minutes on day 1. Patients then undergo planned definitive surgery (lumpectomy or mastectomy) on day 10-23. Tissue and blood samples from the initial biopsy and definitive surgery are collected to measure changes in biomarkers of tumor growth and metastasis, immunologic function, and the expression of genes important to breast cancer progression and metastasis.

After completion of study treatment, patients are followed up at 40-44 days.

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 9

Inclusion Criteria

Postmenopausal women
Diagnosis of early stage, invasive ductal carcinoma (for which a lumpectomy or mastectomy is planned prior to systemic therapy)
Estrogen receptor (ER)/progesterone receptor (PR) positive tumor (as confirmed by City of Hope Pathology Department if done on the outside) or
Biopsy proven ER/PR positive tumor
Ability to provide informed consent

Exclusion Criteria

Tumor that lacks both estrogen and progesterone receptors
Patients who will receive neoadjuvant therapy prior to definitive surgery
Bisphosphonate therapy currently or within the past 12 months
Regular use of anti-inflammatory agents, with the exception of a baby aspirin regimen per principal investigator's (PI's) discretion
Renal impairment as determined by a creatinine clearance < 60 ml/min as calculated by the Cockcroft-Gault formula using the patient's actual weight
Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures
Recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (zoledronic acid)	laboratory biomarker analysis	Patients receive a single dose of zoledronic acid 4 mg IV over 15 minutes on day 1. Patients then undergo planned definitive surgery (lumpectomy or mastectomy) on day 10-23. Tissue and blood samples from the initial biopsy and definitive surgery are collected to measure changes in biomarkers of tumor growth and metastasis, immunologic function, and the expression of genes important to breast cancer progression and metastasis. zoledronic acid: Given IV laboratory biomarker analysis: Correlative studies therapeutic conventional surgery: Undergo definitive lumpectomy or mastectomy
Treatment (zoledronic acid)	therapeutic conventional surgery	Patients receive a single dose of zoledronic acid 4 mg IV over 15 minutes on day 1. Patients then undergo planned definitive surgery (lumpectomy or mastectomy) on day 10-23. Tissue and blood samples from the initial biopsy and definitive surgery are collected to measure changes in biomarkers of tumor growth and metastasis, immunologic function, and the expression of genes important to breast cancer progression and metastasis. zoledronic acid: Given IV laboratory biomarker analysis: Correlative studies therapeutic conventional surgery: Undergo definitive lumpectomy or mastectomy
Treatment (zoledronic acid)	zoledronic acid	Patients receive a single dose of zoledronic acid 4 mg IV over 15 minutes on day 1. Patients then undergo planned definitive surgery (lumpectomy or mastectomy) on day 10-23. Tissue and blood samples from the initial biopsy and definitive surgery are collected to measure changes in biomarkers of tumor growth and metastasis, immunologic function, and the expression of genes important to breast cancer progression and metastasis. zoledronic acid: Given IV laboratory biomarker analysis: Correlative studies therapeutic conventional surgery: Undergo definitive lumpectomy or mastectomy

Primary Outcome Measures

Name	Time	Method
Mean (SE) Change From Pre-Treatment Baseline in (Log)pg/mL of Biomarker, by Time, Adjusted for Level at Baseline	"48-72 hrs" and "Surgery (10-23 days)"	After the trial's premature closure, no data were collected for the primary endpoints; however, data on 14 of 30 secondary endpoints were obtained and are summarized below. Serum level (pg/mL) per biomarker was log-transformed. Change from baseline over time was evaluated using a generalized linear mixed model where follow-up time was represented by terms for the sequence of post-baseline samples or for (log)day on study. To recognize regression to the mean across repeated samples, a term for biomarker level at baseline, with or without interaction by time, was included when it improved the model's fit to the observed data. With 14 biomarkers sampled twice after baseline, there were 28 evaluations of change in biomarker level with exposure to study drug. Therefore, to control the False Discovery Rate (FDR), only evaluations that maintained the study's FDR at no more than 5 percent were accepted as true.

Secondary Outcome Measures