DNA in Predicting Response After Systemic Therapy in Women With Metastatic Breast Cancer

OBJECTIVES:

Primary

• Identify a panel of methylated gene markers in serum from women with metastatic breast cancer that is significantly different from that observed in healthy participants.
• Assess changes in a panel of methylated gene markers from baseline, after 3-4 weeks, and after 9-12 weeks of systemic therapy in patients with metastatic breast cancer.
• Determine the potential effects of common exposures (i.e., alcohol, smoking, medications, and dietary factors) on patterns of serum methylation in patients with metastatic breast cancer and in healthy participants.
• Develop a predictive model using DNA methylation profiles in serum that predicts clinical outcome for an individual patient with metastatic disease.

Secondary

• Correlate circulating tumor cells (CTCs) with clinical outcome in patients with metastatic breast cancer.
• Correlate CTCs with serum methylation in these patients.
• Determine if the addition of CTCs to serum methylation results in an improved predictive model.

OUTLINE: This is a prospective, multicenter study.

Patients and healthy participants fill out health assessment questionnaires at baseline, week 3-4, and week 9-12.

Patients undergo blood collection for methylated marker analysis at baseline, weeks 3-4, and weeks 9-12 and circulating tumor cell levels at baseline and weeks 3-4. Healthy participants undergo blood collection for methylated marker analysis at baseline. An additional cohort of healthy participants undergo follow-up blood collection ≥ 1 week after baseline.

DNA methylation is measured by quantitative multiplex methylation-specific polymerase chain reaction (QM-MSP) assay.

After completion of study procedures, patients are followed every 3-4 months.

PROJECTED ACCRUAL: A total of 150 patients and 150 healthy participants will be accrued for this study.

DISEASE CHARACTERISTICS:

• Meets 1 of the following criteria:

• Histologically and/or cytologically confirmed stage IV adenocarcinoma of the breast (patient)
• No diagnosis of an abnormal breast biopsy (including atypical ductal or lobular hyperplasia), or new diagnosis of breast cancer or breast cancer recurrence within the past five years (healthy participant)
• Evidence of disease progression AND initiating a new systemic treatment regimen with trastuzumab (Herceptin®), chemotherapy, endocrine therapy, or investigational agent(s) (patient)

• Treatment may be given as a single agent or in combination
• Measurable or evaluable disease (patient)

• Measurable disease is defined as ≥ 1 measurable lesion identified by RECIST criteria
• Patients with evaluable disease only must have ≥ 1 tumor marker (e.g., carcinoembryonic antigen, CA 27-29, or CA 15-3) above normal level
• Treated brain metastases (surgery or radiation therapy) allowed provided patient has evidence of disease stability or presence of other site(s) of measurable or evaluable disease (patient)

• No leptomeningeal disease
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Female
• Menopausal status not specified
• ECOG performance status 0-2
• No known cancer within the past 5 years other than basal cell or squamous cell carcinoma of the skin and/or adequately treated cervical cancer (healthy participant)
• Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Prior therapy in the preoperative, adjuvant, and/or metastatic setting allowed

• Any number of prior regimens in any setting allowed
• No prior radiation therapy to the only site of disease unless there is evidence of post-radiation disease progression
• No selective estrogen receptor modulator or aromatase inhibitor for breast cancer prevention or therapy within the past 12 months (healthy participant)
• Prior or concurrent use of raloxifene for osteopenia or osteoporosis therapy allowed (healthy participant)
• Concurrent participation in another clinical trial, including one involving an investigational agent(s), allowed