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