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

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 10-14 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 10-14.
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.

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)